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Do I Have Cancer

This ebook from medical practitioner and family doctor Dr. Parajuli gives you all of the signs and symptoms that you need to know in order to catch cancer in the very early stages and protect yourself from it. You don't have to worry about if you have cancer anymore, and better yet you don't have to spend thousands of dollars to make sure of that either! All it takes is a bit of knowledge and you are on your way! This book also teaches about other aspects of cancer patients, such as how to live with different kinds of cancer, how to prepare yourself mentally to accept this reality if it IS a reality for you, and how to deal with doctors and insurance companies. This book is easy to read and in PDF format, so you don't have to worry at all about reading it. Make it easy on yourself! More here...

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Cancer Drug Discovery and Development Beverly A Teicher Series Editor

Matrix Metalloproteinase Inhibitors in Cancer Therapy, edited by Neil J. Clendeninn and Krzysztof Appelt, 2000 9. Tumor Suppresor Genes in Human Cancer, edited by David E. Fisher, 2000 8. Farnesyltransferase Inhibitors in Cancer Therapy, edited by Said M. Sebti and Andrew Hamilton, 2000 7. Platinum-Based Drugs in Cancer Therapy, edited by Lloyd R. Cancer and Other Diseases, edited by J. Silvio Gutkind, 2000 5. Apoptosis and Cancer Chemotherapy, edited by John A. Hickman and Caroline Dive, 1999 4. Antifolate Drugs in Cancer Therapy, edited by Ann L. Jackman, 1999 3. Antiangiogenic Agents in Cancer Therapy, edited by Beverly A. Teicher, 1999 2. Anticancer Drug Development Guide Preclinical Screening, Clinical Trials, and Approval, edited by Beverly A. Teicher, 1997 1. Cancer Therapeutics Experimental and Clinical Agents, edited by Beverly A. Teicher, 1997

Familial Breast Ovarian Cancer

Familial Breast and Ovarian Cancer This book surveys the profound and far-reaching ramifications that have arisen from the very significant advances in our understanding of the genetic basis of familial breast and ovarian cancer. Written by international experts from Europe and North America, it provides the busy clinician with a contemporary and wide-ranging guide to the latest developments in the diagnosis, genetics, screening, prevention and management of familial breast cancer. In this rapidly advancing field, this book provides an unrivalled source of information, including sections on ethical and insurance issues and the different cultural aspects of breast cancer. The use of recently devised cancer genetics clinics and different referral criteria and patterns to these clinics are also detailed. This accessible book will be of immense value to all clinical geneticists, oncologists and healthcare professionals involved in screening and counselling programmes.

Services for cancer genetics

Cancer genetics is a new field and the organization of services in this area may be initiated by clinical genetics services or through oncology and other departments, where individuals with a special interest in cancer genetics arrange to see individuals with a family history of cancer, estimate their cancer risks and arrange surveillance and genetic testing as appropriate. In many parts of Europe, cancer genetics clinics have been established for many years, and most specialized genetic counselling for cancer susceptibility is organized from genetics centres. However, the organization and quality of such services vary, depending on the economic status and healthcare systems of the country. There is increasing awareness that education and referral guidelines for primary care physicians are important. This would allow a collaborative relationship to be developed with primary healthcare services, helping them act as gatekeepers for the prioritization of referrals for genetics services....

Chemical Carcinogenesis

One hundred and forty years after Dr. Pott's report of the association of soot from the combustion of coal with epidermal cancer of the scrotum, an experimental basis for Pott's clinical observation was reported. In 1915, the Japanese pathologists Yamagawa and Ichikawa described the first production of skin tumors in animals by the application of coal tar to the skin. These investigators repeatedly applied crude coal tar to the ears of rabbits for a number of months, finally producing both benign and, later, malignant epidermal neoplasms. Later studies demonstrated that the skin of mice was also susceptible to the carcinogenic action of such organic tars. During the next 15 years, extensive attempts were made to determine the nature of the material in the crude tars that caused malignancy. In 1932, Kennaway and associates reported the production of carcinogenic tars by pyrolysis of simple organic compounds consisting only of carbon and hydrogen (cf. Kennaway, 1955). In the early...

Studies of familial breast cancer

It has been recognized for many years that there is an association in certain families between breast and ovarian cancer. The risk for epithelial ovarian cancer was found to be significantly elevated in patients with first-degree relatives affected with breast cancer (twice the population risk) (Muderspach, 1994 Claus et al., 1996). Similarly, the risk for breast cancer was found to be elevated in patients who had first-degree relatives with ovarian cancer. Following international studies of large families with an excess of both early-onset breast cancer and of ovarian cancers, Mary Clair King's group demonstrated linkage between inherited susceptibility to early-onset breast cancer and a polymorphic marker on chromosome 17q21.3 (Hall et al., 1990). Predisposition to breast and ovarian cancer was also found with this locus in many families around the world, but it was also clear that other families existed with an excess of early-onset breast cancer that did not segregate with this...

Chemical Carcinogenesis by Mixtures Defined and Undefined

While most of this chapter concerns itself with the carcinogenic action of specific chemicals, it is relatively unusual that an individual is exposed to a single carcinogenic agent. Despite this fact, relatively few detailed studies on mixtures of carcinogenic chemicals have been carried out experimentally. The most common environmental mixtures are those seen in tobacco smoke and other combustion products, including engine exhaust and air pollution (Mauderly, 1993). Interactions between chemicals in mixtures may be additive, multiplicative, or inhibitory (Mumtaz et al., 1993). In the examples given above, however, the exact chemical nature of components in tobacco smoke or air pollution is not always known, nor are their amounts determined. Thus, one may be forced to deal with a mixture as if it were a single entity or, if the constituents are known, to treat the effects of the mixture in some empirical way usually related to the most potent component of the mixture. Studies on the...

Genes implicated in breast cancer predisposition

More than 500 sequence variations have been identified in BRCA1, and of these, more than 80 of all BRCA1 mutations are frameshift or nonsense mutations that alter the codon reading frame and result in a 'stop' codon producing a premature protein termination (Futreal et al., 1994 Gayther et al., 1995 FitzGerald et al., 1996 Szabo and King, 1997 Liede et al., 1999). Genetic susceptibility to breast cancer is thought to occur when one BRCA1 allele is inactivated in the germline cancer Collaborative studies by the Breast Cancer Linkage Consortium (BCLC) have examined multiple families with germline mutations in BRCA1 and BRCA2 to establish the penetrance of mutations in these genes and the risks of other cancers (Ford et al., 1994 Ford et al., 1998 Puget et al., 1999a) (Figure 2.1). These studies suggest that carriers of mutations in BRCA1 have an associated cumulative breast cancer risk of 80-85 by age 80 years. Once affected with a first breast cancer, such gene carriers have a...

Metabolism Of Chemical Carcinogens In Relation To Carcinogenesis

Although the discovery that polycyclic hydrocarbons and other chemical compounds could produce cancer gave hope that the complete understanding of the nature of neoplasia might be at hand, more than 60 years have elapsed since those findings appeared and we still seem to be a long way from such an understanding. The excretory metabolites of polycyclic hydrocarbons were found to be hydroxylated derivatives, which usually had little or no carcinogenic activity. Similarly, hydroxylation of the rings of the aromatic amine carcinogens, such as 2-acetylamino-fluorene (AAF) and 4-dimethylaminoazobenzene, usually resulted in a complete loss of activity. The enzymatic production of these more polar metabolites facilitated the further metabolism and excretion of the parent compounds. The different classes of chemical carcinogens have no single common structural feature (Figures 3.1, 3.3, and 3.4). Thus, the complexity of the variety of chemicals capable of inducing cancer posed a striking...

Age of Cancer Incidence

Perturbations of the genetic and environmental causes of cancer shift the age-specific curves of cancer incidence. We understand cancer to the extent that we can explain those shifts in incidence curves. In this chapter, I describe the observed age-specific incidence patterns. The following chapters discuss what we can learn about process from these patterns of cancer incidence. The first section introduces the main quantitative measures of cancer incidence at different ages. The standard measure is the incidence of a cancer at each age, plotted as the logarithm of incidence versus the logarithm of age. Many cancers show an approximately linear relation between incidence and age on log-log scales. I also plot the derivative (slope) of the incidence curves, which gives the acceleration of cancer incidence at different ages. The patterns of acceleration provide particularly good visual displays of how cancer incidence changes with age, giving clues about the underlying processes of...

Chemical Structure and Chemical Carcinogenesis

Knowledge of the metabolic activation of chemicals has dramatically advanced our understanding of carcinogenic mechanisms underlying the extreme diversity of chemical structures involved in cancer development. The relationship of chemical structure to carcinogenic activity plays a significant role in the potential identification and mechanism of potential chemical carcinogens. Computerized databases of carcinogenic and noncarcinogenic chemicals have been developed to relate structure to carcinogenic activity in a variety of carcinogens (Enslein et al., 1994 Rosenkranz and Klopman, 1994).

Dna Rna And Protein Adducts Resulting From Their Reaction With Ultimate Carcinogenic Forms

One of the most intriguing problems that experimental oncologists have considered in the area of chemical carcinogenesis is the characterization of the covalent compounds resulting from reactions between the ultimate metabolite of a chemical carcinogen and a macromolecule. The structures of several different chemical carcinogens covalently bound or adducted to protein and nucleic acids are shown in Figure 3.12. For the detailed chemistry of the reactions involved in the formation of such adducts, students are referred to several of the references, especially those by the Millers (1970, 1978), Weisburger and Williams (1982), Hathway and Kolar (1980), and Dipple et al. (1985). Guanine is the nucleic acid base that has been found to react most avidly with the ultimate forms of chemical carcinogens. As noted in Figure 3.12, the reaction of the ultimate form of N-methyl-4-aminoazobenzene with polypeptides involves a demethylation of

Mutagenesis and Carcinogenesis

As noted above, the majority of chemical carcinogens must be metabolized within the cell before they exert their carcinogenic activity. In this respect, metabolism of some chemicals results in a bioactivation instead of elimination. Thus, metabolic capabilities may underlie how a substance that is not carcinogenic for one species may be carcinogenic for another. This becomes important for carcinogen testing in whole animals for both hazard identification and risk assessment. Such considerations impact directly on the choice of the most sensitive species or the species most similar to humans for these evaluations. Since chemical carcinogens are reactive per se or are activated by metabolism to reactive intermediates that bind to cellular components including DNA, their electrophilic derivatives which bound to a variety of nucleophilic (electron-dense) moieties in DNA, RNA, and protein were considered the ultimate carcinogenic form of the compounds of interest (see above). Several lines...

Hormonal Carcinogenesis

The concept that hormones may be a causative factor(s) in the development of specific types of neoplasms was first pointed out by Beatson (1896), who at the end of the last century suggested a relation between breast cancer and the ovary. Within the past 40 years, this concept has been reinforced by data from several experimental systems, and within the past 15 years the role of hormones in the genesis of cancer in humans has become a subject of considerable interest.

Table 22 Important clinical factors in the diagnosis of thyroid cancer

Dysphagia, dysphonia, dyspnea, hoarseness or hemoptysis may all reflect esophageal or tracheal involvement by a thyroid cancer. These symptoms can also occur with benign causes of thyroid enlargement, such as hemorrhagic degeneration or subacute thyroiditis. Other symptoms that may serve as a clue regard hyperthyroidism (weight loss, nervousness, heat intolerance) or hypothyroidism (weight gain, depression, fatigue, cold intolerance). Nodules associated with hyper-thyroidism are usually benign functioning adenomas whereas a nodule in a patient with hypothyroidism is often caused by autoimmune thyroiditis.

Hormonal Relationships in the Development of Human Cancer

Although hints and reports of a role for hormones and the causation of human cancer had appeared over the past several centuries, the first practical application of hormones in oncology was their use in the therapy of specific human neoplasms. The first practical application to the human of what little knowledge existed at the time was the demonstration by Huggins and Hodges of the partial androgen dependence of many human prostatic cancers, as evidenced by the beneficial effects of orchiectomy or synthetic estrogens in many patients even with meta-static disease (Huggins and Hodges, 1941). Since then, significant evidence has developed to indicate a role for hormones in the development of several common human neoplasms. Miller (1978) pointed out such a relationship with breast, ovarian, endometrial, and prostate cancer in the human. More recently Henderson and colleagues (Henderson et al., 1988) have presented reasonable evidence to argue for a major role of estrogens in cancers of...

Mechanistic Considerations In Hormonal Carcinogenesis

Since all hormones are chemicals, their induction of neoplasia might be considered in the same light as chemical carcinogens discussed earlier (Figures 3.1, 3.3, 3.21, and 3.22). However, there is substantial evidence that, with few exceptions, the carcinogenic action of hormones is intimately associated with their hormonal activity. Thus, in determining the mechanism of carcino-genesis by hormones, it is important to consider the mechanisms by which these chemicals induce their hormonal effects on cells and tissues. Unlike most chemical carcinogens, hormones in general need not be metabolized to exert their hormonal effects on cells. Rather, in all known instances, hormonal effects on cells are mediated through direct interaction of the hormone with a specific receptor molecule. A simplified diagram of the location of such receptors in cells is seen in Figure 3.23. In general, hormone receptors may occur either as soluble proteins dissolved in the internal milieu of the individual...

Breast Cancer and Its Treatment

It is the second leading cause of cancer death among women (representing 15 of all cancer deaths), compared to 25 of cancer deaths from lung cancer (American Cancer Society ACS 2004). Estimated deaths from breast cancer in 2003 were 39,800 for women and 400 for men. Mortality rates for breast cancer declined significantly in recent years, mostly among young women, both white and black, falling 1.4 annually in 1989-1995 and then at a rate of 3.2 annually. Survival for women with breast cancer varies as a function of the stage of the disease at diagnosis. The ACS data show 5-year relative survival rates of 86 for all stages, 97 for local, 78 for regional, and 23 for distant (or metastasized) cancers. The ACS, relying on the SEER staging system of the National Cancer Institute, defines local-stage tumors as cancers that are confined to the breast regional-stage tumors have spread to surrounding tissue or nearby lymph nodes and distant-stage tumors have...

The Need For Biomarkers In Bladder Cancer

Bladder tumors are pathologically stratified based on stage, grade, tumor size, presence of concomitant carcinoma in situ, and multicentricity.1-2-1 The chances of tumor progression are augmented with the increase of these pathological variables. Pathologically, most bladder tumors are transitional cell carcinomas. There is, however, increasing recognition of the prognostic importance associated with the metaplastic variants displaying squamous and glandular differentiation as part of their clonal evolution. The power of these histopathological variables and the tumor node metastases (TNM) categorization, in defining the clinical subtypes of bladder cancer and predicting the clinical outcome of individual patients, has certain limitations. Within each stage, it has been very difficult to identify clinically useful parameters that can predict risk of disease recurrence or progression. Numerous biological markers have been described for bladder cancer, some correlating with tumor stage...

Microarrays As Target Identification Tools In Cancer

Microarrays constitute a group of technologies characterized by the common availability of measuring hundreds or thousands of items, including DNA sequences, RNA transcripts, or proteins, within a single experiment using miniaturized devices. Hybridization-based methods and the microarray format constitute together an extremely versatile platform provided for both static and dynamic views of DNA structure, as well as RNA and protein expression patterns in cultured cancer cells and tumor

Bladder Cancer Studies Using In Vitro Models

Expression profiling using bladder cancer cell lines has been used to gain insight into the molecular events associated with clinical disease states, assigning potential functional roles to novel genes in both tumorigenic and tumor progression processes. Certain studies have focused on gene and pathway discovery associated to genistein 10 or 5-aza-2'-deoxycytidine 11 exposure. Other reports describe the functional classification of genes comparing the expression patterns of p53-mediated apoptosis in resistant tumor cell lines versus sensitive tumor cell lines using cDNA arrays, 12 or the expression patterns of a metastatic variant cell line to the respective parental invasive cells. 13 Many molecular targets involved in bladder cancer progression have been identified in these studies. Comprehensive analyses using clinical specimens will also elucidate the clinical utility of these targets as biomarkers for patients with bladder cancer. An attempt to tumor subtypes classification of...

Bladder Cancer Studies Using Clinical Specimens

Microarray analyses have been used to correlate changes in the expression of specific genes and groups of genes within distinct bladder subclasses. Such signature genes would ideally provide a molecular basis for classification, yielding insight into the molecular events underlying different clinical bladder cancer phenotypes. The first report monitored the expression patterns of superficial and invasive tumor cell suspensions prepared from individuals and pools of normal and bladder tumors of tumors of different stages such as from pTA grade I and II and pT2 grade III and IV bladder cancer specimens. 15 Hierarchical clustering of gene expression levels grouped bladder cancer specimens based on tumor stage and grade. The most significant functional genes included those involved in cell cycle, cell growth, immunology, adhesion, transcription, and protein metabolism. Superficial papillary tumors showed increased transcription factor and ribosomal levels, as well as proteinase encoding...

Physical Carcinogenesis Radiation Carcinogenesis

Perhaps the first documented example of the induction of neoplasia by ionizing radiation was that of atypical epithelial hyperplasias and malignant epitheliomas observed on the hands of radiologists and scientists using x-ray devices and radium within a few years after their discovery near the turn of this century. In these cases, the human being was the experimental victim of radiation carcinogenesis. Fortunately, scientists rapidly became aware of the dangers of ionizing radiation and took precautions to prevent its effects in humans. Radiant energy in our universe comes in a variety of general types, all related to the wavelength and frequency of the waves. A diagram of the electromagnetic spectrum is seen in Figure 3.26. With our present-day knowledge, there is no solid evidence that radiant energy of wavelengths greater than 5 x 10-5 cm is carcinogenic. However, ultraviolet, Roentgen or x-rays, and gamma rays have carcinogenic effects. In addition, high-energy particles such as...

Experimental Radiation Carcinogenesis

Although humans were the first experimental animals in which radiation-induced cancer was demonstrated, there are now many examples of the experimental induction of cancer by radiation. The experimental induction of skin cancer in mice by Findlay (1928) and later by Rusch

Doseresponse Relationships In Chemical And Physical Carcinogenesis

The effectiveness of a chemical or physical carcinogen in inducing neoplasia is not only dependent on its structural and energetic properties, but also on the administered dose and the potency of the agent itself. The latter characteristic for chemicals will be considered in a later chapter (Chapter 13) and to some extent has already been spoken to for radiation carcinogenesis in relation to LET and RBE (see above). Both practical and theoretical considerations of quantitative aspects of chemical and radiation carcinogenesis must be taken into account in considering the effect of a specific dose of such agents in producing neoplasia. Theoretical dose-response curves are given in Figure 3.27, in which the dose in arbitrary units produces an effect, in this case cancer. The numbers on each of the curves indicate the number of hits that were required to produce that specific effect. Thus, if only a single hit is required for the production of cancer by radiation or by the ultimate form...

Are endometriosis and cancer related

Having endometriosis is bad enough, but the thought that endometriosis may increase your risk of developing certain types of cancer is even worse. Even though studies are inconclusive about a definite link between certain cancers and endometriosis, research indicates that endometriosis doesn't increase the general risk of cancer. However, endometriosis may increase the risk of certain rare cancers. According to a very large (64,000 women) retrospective study (researchers looked at statistics only after the study was complete) in Sweden, the cancers that are more prevalent in women with endometriosis are i Ovarian cancer i Certain endocrine cancers i Certain brain cancers i Women who had endometriosis and a hysterectomy showed no increase in ovarian cancer over the general population. i Younger women who developed endometriosis between the ages of 20 and 40 had a higher risk of getting ovarian cancer than other age groups. i Women with endometriosis developed cancer at a younger age...

Cancer susceptibility

During the shortened lifetimes of AT homozygotes, 38 develop a malignancy, usually lymphoid. This represents a 61-fold and 184-fold increase in Euro-American and Afro-American patients, respectively. About half of the malignancies observed are lymphomas, usually of the B cell type. Leukemias account for another quarter of the malignancies. These are usually T cell leukemias. Young AT patients develop a less aggressive T cell leukemia than older patients, who develop a prolymphocyte-leukemia (T-PLL) the latter was formerly described as T-CLL because the cells histologically resemble those of chronic lymphocytic leukemia. However, the T-PLL cells are T cells. Myeloid leukemias have not been described in AT patients. AT heterozygotes are also cancer prone, although not to the extent that homozygotes are. Breast cancer was observed to be five-fold higher among heterozygotes in US families. Based on this observation and an estimated carrier frequency of 1 , it has been postulated that...

Infectious Agents As Causes Of Cancer

Clemmesen, 1978) reported the occurrence of papillomas of the stomach in rats infected with Spiroptera, a small parasitic worm. The intermediate host of the parasite was the cockroach. By feeding either cockroaches infested with the worm or the worm itself to rats, Fibiger was able to produce lesions that were interpreted as papillomatous growths of the stomach. In 1927, Fibiger was awarded the Nobel Prize for this work, the first such award for cancer research. Unfortunately, later studies did not bear out Fibiger's thesis that the stomach lesions were neoplasms but rather indicated that the tumors resulted from the combination of a deficiency of vitamin A in his experimental animals and the infestation by the parasite. Despite this setback, over the years many investigators have reported that certain biological factors are important in the causation of cancer. The parasitic worm Spirocerca lupi is associated with esophageal sarcomas in the dog...

Viruses As Causes Of Cancer

Viruses are ubiquitous obligate intracellular parasites. Because viruses replicate in and are dependent upon their host cells, they use the rules, signals, and regulatory pathways of the host cell. Viruses subvert and perturb normal cellular mechanisms and pathways as a means of replicating. These perturbations can have dire consequences for the host cell. It is not an uncommon consequence of a viral infection for the host cell to die. Though less common, viral infection can change or transform a normal cell into a neoplastic one, ultimately leading to a cancer. In fact, there is compelling evidence that several different human cancers are caused by viral infection (Chapter 12). Clearly, appreciation of this relationship can be critical in the epidemiological control of cancer. Prevention or cure of a viral infection may lower the incidence of the cancer induced by a given viral agent. Knowledge of cancer-causing viruses has served a second very important function. These viruses cause...

Sources of Evidence Linking Diet and Cancer

Laboratory scientists have known since the early twentieth century that various nutritional manipulations can influence the occurrence of tumors in animals. Despite this discovery of the relationship between diet and cancer in animals, widespread interest in the study of diet and cancer in humans did not develop until more recently when the large international differences in cancer rates were correlated with variations in dietary factors. In fact, investigators have found strong correlations between estimated per capita fat consumption and breast cancer rates internationally, raising the possibility that dietary fat may have an important role in the etiology of breast cancer. Other observations such as those demonstrating that migrating populations adopted, sooner or later, the cancer rates of their new host population strengthened the evidence that international differences were the result not of genes, but of noninherited factors, including diet. The study designs used to...

Summary of Known Relations between Diet and Cancer

A wealth of studies since the 1970s have clearly documented the relations between diet and a growing number of cancers (Table 2). Convincing evidence based on consistent findings from epidemiological studies conducted in diverse populations now shows that diet is an established cause of prostate, breast, digestive tract, airway, and urinary tract cancers. With these rich epidemiological data we can more confidently conclude that some 30 of cancer is attributable to diet. Public health officials have taken the accumulated evidence and developed strategies for minimizing cancer risk. Among these recommendations is a diet high in vegetables, fruits, and legumes and low in red meat, saturated fat, salt, and sugar. They suggest that carbohydrates be consumed as whole grains such as whole meal bread and brown rice rather than as white bread and rice. Any added fats should come from plant sources and should be unhydrogenated, an example being olive oil, which may potentially be beneficial....

Clinical cancer genetic management

The two most serious, and established, component tumours in CS are breast cancer and non-medullary thyroid cancer for affected females and males. Endometrial cancer is now believed to be a component of CS as well. Patients with CS or those who are at risk of CS should undergo surveillance for these three cancers. Beginning in their teens, these individuals should undergo annual physical examinations, paying particular attention to the thyroid examination. Beginning in their mid-twenties, women with CS or those at risk of it should be encouraged to perform monthly breast self-examinations and to have careful breast examinations during their annual check-ups. The value of annual imaging studies is unclear as no objective data are available. Nonetheless, we usually recommend annual mammography and or breast ultrasounds performed by skilled individuals in at-risk women, beginning at age 30 years or 5 years younger than the earliest breast cancer case in the family, whichever is earlier....

Small Intestine Cancer

Cancer of the small intestine is very rare the age-adjusted incidence is approximately 1.4 per 100 000 less than 2 of all gastrointestinal malignancies. The incidence of small intestine cancer is higher in Maori of New Zealand and There are four types of small intestine cancer, each with unique characteristics adenocarcinoma, carcinoid, lymphoma, and sarcoma. In Western developed countries, approximately 30-40 of small intestine cancer is adenocarcinoma, predominantly in the duodenum, and carcinoid and lymphoma occur more often in the jejunum or ileum, whereas sarcoma may develop anywhere in the small intestine. In developed countries, lymphoma is very rare and occurs more often in older people with relatively good survival. In contrast, in developing countries, lymphoma is the main type of small intestine cancer, and it occurs more often in younger individuals, anywhere in the small intestine, with poor survival. Hence, prognosis of small intestine cancer depends on the type,...

Carcinogens Produced by Food Processing

Despite the widespread occurrence of potentially carcinogenic chemicals in the plant kingdom, most foodstuffs contain only low levels of these chemicals. However, it has now been recognized that a number of processes used in food preparation processing can introduce significant amounts of carcinogens into the food or the local environment. The most widely studied of these processes are preservation of meats and fish by salting or smoking grilling or broiling of meats, and cooking in vegetable oils. Traditional methods for preserving meat and fish involve either salting or smoking. Epidemiolo-gical evidence has been found for an association between an increased incidence of cancer of the mouth and pharynx and intake of salted meat. It seems likely that a reaction between sodium nitrate and or nitrite used for preserving the meat and alkylamides present in the meat results in the formation of N-nitrosamines and nitrosamides. These compounds have been shown to be potent carcinogens in...

Mechanisms of Carcinogenicity

Chemical carcinogens induce neoplasia by a wide range of mechanisms involving either interaction with the hereditary material of the organism or interference with one of the many cellular control systems. The former compounds, known as geno-toxic carcinogens, interact directly with DNA, resulting in a permanent heritable change to a cell following replication (i.e., an altered genotype). In contrast, nongenotoxic (epigenetic) carcinogens do not interact directly with DNA but cause cancer by other mechanisms. The enzyme system considered to be mainly involved in the activation of chemicals to carcinogenic species is the so-called mixed function oxidase system. This enzyme complex is centered on cytochrome P450 and is present in most, if not all, of the organs of the body. The enzyme system consists of a very large family of related isoenzymes of differing substrate specificity and has a widespread distribution in the animal kingdom. Early work with this enzyme system suggested that...

Metabolic Activation of Epigenetic Carcinogens

Since there is no common mechanism describing the action of epigenetic carcinogens, generalizations concerning the effect of metabolism on the activity of chemicals acting by a nongenotoxic mechanism are not possible. The activity of a number of epige-netic carcinogens is reduced as a result of metabolic activation, although in the case of one group of epigenetic carcinogens that produce renal tumors in the rat by binding to and preventing the degradation of a specific kidney protein, alpha-2-microglobulin, metabolic activation is required for carcinogenic activity. Compounds acting by this mechanism include isophorone and D-limonene, which are present naturally in many fruits. Similarly, a wide range of structurally diverse chemicals induce liver tumors in rodents due to their ability to induce the proliferation of hepatic peroxisomes. Food contaminants such as phthalate diesters, which leach out of packaging materials, fall into this category, although no naturally occurring food...

Carcinogenicity Tests Animal Bioassays

As the mechanism of carcinogenesis in both humans and animals is not well understood, the only acceptable procedure for determining whether a chemical is likely to be a carcinogen is the examination of experimental animals exposed to the suspect material under carefully controlled conditions. This procedure relies on the assumption that animals will behave in essentially the same way as humans to carcinogen exposure, i.e., the mechanism of tumor induction will be similar in both animals and humans. Mechanistically based, short-term tests for carcinogenicity prediction not involving experimental animals are still a distant and elusive goal. The basic approach for carcinogenicity testing involves administering the test material to two suitable animal species for a considerable proportion of their natural lifespan. Because of their small size and relatively short life expectancy, the rat and mouse are the species of choice, although the hamster is occasionally used. In the US, inbred...

The Etiology of Cancer Germline Genetic Factors

The predominant environmental factors in the causation of cancer include chemicals, ionizing and ultraviolet radiation, as well as specific infectious agents, predominantly viruses. Although the majority of these agents may have as a principal component of their etiological mechanism some interaction with and or alteration of the cellular genome, neoplastic disease resulting from the action of such agents is not generally thought of as hereditary or genetic disease. The term hereditary or genetic disease usually connotes an abnormality transmitted through the germline from parent to offspring. In this sense it is reasonable to state that, in considering all cases of human neoplasia, most cancers are not the direct result of heredity but are acquired through an interaction of the host with the environment. However, the interaction of the environment with the genetic composition of the host, either directly or indirectly through the regulation of the expression of the host genome, is...

Dominant And Recessive Disorders Associated With A High Incidence Of Human Cancer

Although the total number of cases of human cancer with a distinct Mendelian genetic mode of inheritance is small relative to the incidence of neoplasia in general, a variety of autosomal and sex-linked disorders, both dominant and recessive, are associated with or clearly causative of specific neoplasms both in humans and in animals. For obvious reasons, the largest number of examples of such conditions have been described and studied in humans. Some of these are listed in Table 5.1, with the associated neoplasm(s) and the mode of inheritance of the specific condition.

And Animal Models Of Human Cancer

Recent SAGE studies were performed using a p53 null mouse model of mammary epithelial in vivo preneoplastic progression. This led to the identification of several new and unsuspected targets directly or indirectly dysregulated by the absence of p53 in normal mammary epithelium in vivo. These studies also allowed us to analyze the dramatic physiologic effects of hormonal treatment in mammary gland differentiation (45) (database available at In other studies using a mouse model of skin carcinogenesis, the gene expression profile of squamous cell carcinomas induced by UV-light has been compared with that of normal skin (46). In summary, since its inception, the use of SAGE has grown dramatically. The numerous publications using this methodology for a multitude of applications have validated the approach and demonstrated the power of this methodology for the analysis of global gene expression. As discussed, it was used in numerous cancer-related studies and has been particularly useful...

Multistage Progression in Colorectal Cancer

Colorectal cancer provides a good model for the study of morphological and genetic stages in cancer progression (Kinzler and Vogelstein 2002). Various precancerous morphologies can be identified, allowing tissue samples to be collected and analyzed genetically. Figure 3.1 shows the morphology of normal colon tissue. The epithelium has about 107 invaginations, called crypts. Cells migrate upward to the epithelial surface from the dividing stem cells and multiplying daughter cells at Figure 3.2 Morphology of colorectal cancer progression. This classical pathway is characterized by traditional adenoma morphology, slow progression, high adenoma carcinoma ratio, frequent chromosomal instability and aneuploi-dy, and rare microsatellite instability. Particular genetic changes often associate with morphological stage, suggesting that the genetic changes play an important role in driving progression. Approximately 50-85 percent of colorectal cancers follow this pathway. Redrawn from Figure 3...

Spontaneous And Induced Dominant And Recessive Genetic Disorders Associated With High Cancer Incidence In Lower Animals

Until relatively recently, the germline genetics of cancer in lower animals was far less well studied than that in the human with a few specific exceptions in particular, strains of mice where genetic factors could be well controlled. However, specific dominant or recessive genes predisposing to a high incidence of neoplasia have not as yet been frequently seen in animal systems. On the other hand, with the advent of molecular genetic techniques, it has become possible to program genetic factors leading directly to the incidence of specific neoplasms.

Multifactorial Genetics Of Cancer

As indicated above, genetic predisposition to neoplasia resulting from alteration in a single gene locus is a relatively rare cause of cancer in humans as well as in lower animals. A much greater contribution of genetics to the causation of neoplastic disease are those conditions having patterns of inheritance that conform to a polygenic or multifactorial mode of inheritance, recently termed complex traits (Lander and Schork, 1994). Many common chronic diseases of adults (including types of hypertension, coronary heart disease, diabetes mellitus, and schizophrenia) as well as certain developmental defects (including cleft lip and palate, spina bifida, and congenital heart disease) are known to be more frequent in those with family histories of such disorders. A number of these diseases may be due to single gene defects and others to chromosomal abnormalities, but most are the result of multiple genetic and environmental factors combined. In polygenic inheritance, multiple genes at...

Clinical pathological and outcome characteristics of BftCArelated ovarian cancer

Clinicopathological characteristics of ovarian tumour have been evaluated in familial aggregation of ovarian cancers or among patients with BRCA1 2 germline mutation (hereditary ovarian cancer). Few data are available for ovarian cancer associated with other inherited genetic syndromes and will not be discussed further here. This whole topic is discussed in detail in Chapter 7. Early age of onset is often considered to be a hallmark of most of the hereditary cancers. As discussed above, in some studies the average age of onset for familial or hereditary ovarian cancer was significantly lower (about 5 years) than that of ovarian cancer in the general population (Bewtra et al., 1992 Lynch et al., 1993 Piver et al., 1993a Muto et al., 1996 Rubin et al., 1996 Zweemer et al., 1998 Boyd et al., 2000). This significant difference in age of onset has not been found consistently (Narod et al., 1994a Chang et al., 1995 Auranen et al., 1997 Stratton et al., 1997 Johannsson et al., 1998 Gayther...

Genes That Modify Cancer Predisposition

In the earlier part of this chapter we discussed specific genes, abnormalities of which lead to the development of specific neoplasms, usually in a fairly high percentage of affected individuals. However, in multifactorial genetic traits, as noted above, a number of genes may be involved in the expression of a predisposition to neoplastic disease. This may be the case even in those situations where cancer predisposition may result from mutations in a tumor suppressor or proto-oncogene. Obvious proof of this latter statement is the fact that germline inherited mutations in tumor suppressor genes do not result in neoplasms of all tissues, proliferating or not, but usually only in certain tissues of the organism. Presumably, genes expressed in some tissues prevent the

Proto Oncogenes in Multifactorial Cancer Susceptibility

On the basis of studies in animals with carcinogenic retroviruses, one might expect that mutations in proto-oncogenes would be a major cause of germline neoplasia in the human. We have already seen that this is generally not true, with the ret proto-oncogene being the only known example of a causative association with specific human neoplasms (Tables 5.4 and 5.6). Evidence that mutations in proto-oncogenes play any role in a genetic predisposition to neoplasia has been somewhat controversial. In 1987 Krontiris reported that rare alleles of the Ha-ras proto-oncogene were almost exclusively seen in the genomes of cancer patients (Krontiris et al., 1987). Since that time, other studies (Klingel et al., 1991 Ryberg et al., 1992) have shown a

Hereditary nonpolyposis colorectal cancer

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant disorder associated with germline mutations in five mismatch repair genes MSH2, MLH1, PMS1, PMS2 and MSH6 (Lynch and de la Chapelle, 1999). The protein products of HNPCC genes are key players in the correction of mismatches that arise during DNA replication. Mismatch repair (MMR) deficiency gives rise to microsatellite instability (MSI). MSI results from repetitive non-coding DNA sequences of unknown function found throughout the genome. Loss of MMR function may also result in mutations in the coding regions of genes involved in tumour initiation and progression, e.g. APC, KRAS, TP53 and TGFbRII. The so-called 'Amsterdam criteria' are often used to make a clinical diagnosis of HNPCC. According to the classical Amsterdam criteria (Amsterdam criteria I), there should be at least three relatives with colorectal cancer, one relative should be a first-degree relative of the other two, at least two successive...

Do ovarian and breast cancer belong to the tumour spectrum of HNPCC

Watson and Lynch (1993) evaluated the frequency of cancer in 1300 high-risk members of 23 extended kindreds with HNPCC. They reported 13 cases of ovarian cancers (mean age at diagnosis 40 years) in these families, while 3.6 were expected on the basis of the general population incidence (observed expected ratio 3.5, P < 0.001 ). Vasen compared the risk of developing ovarian cancer between carriers of an MLH1 mutation (n 124) and carriers of an MSH2 mutation (n 86) (Vasen et al., 1996). He reported relative risksof 6.35 (95 CI 0.89-45.1) and 7.97 (95 CI 1.1-56.6) for MLH1 and MSH2 mutation carriers, respectively. Aarnio assessed the incidence of cancer in a large series of mutation carriers (predominantly MLH1 mutations) (n 360 183 women, 177 men) known at the Finnish HNPCC registry (Aarnio et al., 1999). He reported a standardized incidence ratio (SIR) for ovarian cancer of 13 (95 CI 5.3-25) and a cumulative ovarian cancer incidence of 12 by age 70 years. In conclusion, several...

Comparative Genomic Hybridization In Cancer Cytogenetics

Genetic alterations associated with neoplasia have been well defined in hematological malignancies by both classical and molecular cytogenetics.1-5'6-1 In contrast, there is significantly less information known about the cytogenetics and molecular cytogenetics of solid tumors. This is because of technical difficulties in the production of metaphase spreads from these tumor cells. Karyotype analysis requires viable, proliferating cells that can be arrested in the metaphase stage of the cell cycle. Cytogenetic analysis of these tumors is often hampered as many solid tumor cells fail to proliferate in vitro. For those tumors that do divide and produce metaphase spreads, the quality of the metaphase spreads is often inadequate to allow for recognition of banding patterns. There is also the question of the significance of the cytogenetic data derived from in vitro tumor cell culture as small subclones in vivo may take advantage of the in vitro conditions and thus the nonproliferating cells...

Retroviruses and Cancer

Retroviruses are among several types of viruses that can induce cancer in the host organism. So-called slowly transforming viruses are exemplified by human T-lymphotropic virus (HTLV), which causes leukemia (a type of blood cancer) in humans. These viruses induce malignancy by a process called insertional mutagenesis. The initial event is thought to be retroviral integration near, and subsequent activation of, a cellular oncogene (c-onc). Examples of c-onc include genes for growth factors, protein kinases, and transcription factors. Harold Varmus and Michael Bishop won the Nobel Prize for physiology or medicine in 1989 for their contributions to the discovery of oncogenes. Acutely transforming retroviruses contain a viral oncogene (v-onc) and induce polyclonal cancers (that is, many different cancer cells are derived in multiple transforming events) at high efficiency within a short time frame (weeks). The v-onc are derived by incorporation and modification (that is, by deletion of...

Alternative Pathways to Colorectal Cancer

Figure 3.3 Genetic changes in HNPCC progression. Approximately 2-4 percent of colorectal cancers follow this pathway. Figure 3.3 Genetic changes in HNPCC progression. Approximately 2-4 percent of colorectal cancers follow this pathway. Most colorectal tumors have either MSI or CIN, but not both. Some form of accelerated mutation may be needed for progression to aggressive colorectal cancer (Jass et al. 2002a Kinzler and Vogelstein 2002). Individuals who inherit defects in MMR develop hereditary nonpoly-posis colorectal cancer (HNPCC) as well as other cancers that together make up Lynch's syndrome (Boland 2002). Some of the genetic steps in HNPCC progression and the rates of transition between stages differ from the classical pathway (Figure 3.3). In another study, Rajagopalan et al. (2002) found that 61 percent of 330 colorectal tumors had either a BRAF or K-RAS mutation, but a tumor never had mutations in both genes. Mutually exclusive mutation of these genes supports the suggestion...

Cancer In The Central Nervous System

Many cancer patients experience impairments of neurocognitive function, including memory loss, dis-tractiblity, difficulty with multitasking, mood disturbance, and a myriad of other symptoms. Patients may also suffer from symptoms that compromise their ability to function adequately, such as fatigue and pain. The etiologies of these problems are diverse and include the direct effects of cancer within the central nervous system, indirect effects of certain cancers (the paraneoplastic disorders), and effects of cancer treatment on the brain. In addition to these cancer-related causes, patients may have co-existing neurologic or

Cns Effects Of Nonbrain Cancer

Certain types of cancers cause brain dysfunction indirectly, causing paraneoplastic brain disorders. It has been estimated that 10 of cancer patients develop such a syndrome. Most commonly associated with small cell lung cancer (SCLC), paraneoplastic brain disorders typically manifest as a diffuse ence-phalomyelitis, including limbic encephalitis, cerebelli-tis, brain stem encephalitis, myelitis, and sensory or autonomic ganglionitis. The cognitive deficits associated with these disorders are of two types. Some patients develop a gradually progressive subcortical dementia that is difficult to distinguish from dementia due to other causes. The second form, paraneoplastic limbic encephalitis, is often characterized by the subacute, progressive onset of anxiety, depression, confusion, hallucinations, recent memory loss, or seizures. The onset of symptoms can precede the diagnosis of cancer even by years. These disorders have an autoimmune pathogenesis and are associated with high titer...

Molecular Genetics Of Cancer

The transformation of a normal to a malignant cell is a multistage process during which the orderly processes of proliferation and differentiation become uncoupled and the balance between proliferation and cell death is disturbed. Cancer cells proliferate unceasingly and do not proceed along normal maturation pathways. Cells cultured in the laboratory undergo two changes in phenotype (physical characteristics) during the route to malignancy Fully transformed cells are biologically 'malignant' but not necessarily 'tumourigenic' or 'metastatic' in an experimental animal. To be so, additional changes of phenotype are required. Clinically, a 'benign' neoplasm, although continually growing, is limited to its primary site. A 'malignant' neoplasm may either form an in situ cancer, showing only unrestrained growth, or invade and metastasize. Only an invasive cancer is truly malignant to its host. Cancer is now regarded as a multi-factoral disease of the cell genome which undergoes a series of...

Pathology of breast cancers in mutation carriers

There are a number of published studies indicating that breast cancers arising in mutation carriers are of higher grade than sporadic cancers (Bignon et al., 1995 Jacquemier et al., 1995 Eisinger et al., 1996 Marcus et al., 1996). Eisenger et al. studied 27 BRCA1-associated breast cancers from 14 families and compared these to sporadic breast cancers, matching for grade. They found an excess of grade III carcinomas in the BRCA1-associated group. Marcus et al. reported the first large series of the pathology of BRCA1-related tumours. They had 90 BRCA1-related breast cancers assigned to the group on the basis of linkage to chromosomes 17q and or the presence of ovarian cancer and male breast cancer. The control set comprised 187 predominantly non-familial cases. They reported that BRCA1-associated tumours were more likely to be of medullary or atypical medullary type, to be of higher grade, to be aneuploid, and to have a higher tumour cell proliferation rate. When adjusted for age, the...

Methylationassociated Silencing In Cancer Progression Involves Abnormal Histone Modifications

It has been widely proposed that the hypermethylated CpG islands will attract methyl-DNA binding activities that will later recruit corepressor complexes that modify the structure of the chromatin to produce a transcriptionally silenced state (18, 38). The presence of different changes in the acetylation, methylation and phosphorylation status of histone, the denominated histone code (39), is fundamental to the determination of the active or silenced status of any given gene. Regarding tumor progression, chromatin immunoprecipitation (ChIP) assays using two antibodies against anti-acetylH4 and anti-dimethylK4 H3 that have been related with transcriptional activation in the mouse skin carcinogenesis model show a drastic loss of acetyl-H4 and dimethylK4-H3 in hypermethylated CpG island promoters, whilst there is significant enrichment in the unmethylated CpG islands in both modifications (25). For instance, the MLH1 promoter that is unmethylated and actively transcribed in all cell...

Molecular pathology of BRCAl2associated breast cancers

Since its discovery in 1960, oestrogen receptor (ER) has become an important prognostic and predictive marker for breast cancer (Osborne, 1998). ER expression is inversely correlated with tumour grade (Henderson and Patek, 1998) hence, BRCA-associated tumours, which are more often of a higher grade than those of sporadic breast cancer, would be predicted to be more often ER-negative. Many studies have shown low levels of ER expression in familial breast cancers (Johannsson et al., 1997 Osin et al., 1998a,b Robson et al., 1998 Armes et al., 1999). This is also true when ER expression in fiRCA-associated tumours is compared with a grade-matched control group (Osin et al., 1998a). In contrast, the expression of ER in BRCA2 tumours appears to be similar to that in sporadic breast cancer tumours (Osin et al., 1998a,b). The detection of ERs immunohis-tochemically does not necessarily reflect their functional competence, and a percentage of cancers expressing ER are known to be resistant to...

Cancer Is a Genetic Disease

The role of somatic mutations in cancer was debated for many years. Witkowski (1990) puts that historical debate in context with a comprehensive time line of developments in cancer research interleaved with developments in basic genetics and molecular biology (see also Knudson 2001). Here, I mention a few of the highlights that provide background for evaluating theories of progression and incidence. Boveri (1914, 1929) often gets credit for the first comprehensive theory of somatic genetic changes in cancer progression (Wunderlich 2002). Tyzzer (1916) used the term somatic mutation to describe events in cancer progression. In the 1950s, Armitage and Doll (1954, 1957) cautiously described the stages of multistage progression as possibly resulting from somatic mutations but perhaps arising from other causes. Burdette (1955), in a comprehensive review of the role of genetic mutations in carcinogenesis, tended to oppose the central role of mutations in progression. In (1969), Fould's...

Dietary Fiber and the Etiology of Cancers Colon and Rectum

This is one long-standing association that has been surprisingly problematic. Early studies on native Africans who consumed an unrefined diet showed them to have a very low incidence of this cancer. Although subsequent studies have shown a negative association between greater fiber intake and lowered risk, it has proved to be relatively weak. Indeed, in one US study there was no real association between fiber intake and cancer susceptibility. Some of the loss of significance seen in this evaluation may reflect the lack of allowance for confounding variables. For example, in a 6-year follow-up of women, the association between low fiber intake and the incidence of colon cancer disappeared after adjustment was made for meat intake. In another study of men, low fiber intake was an independent risk factor for the incidence of adenomatous polyps during a 2-year follow-up period. Fruit and vegetable fiber has been consistently associated with a lower risk of colon cancer, but the...

Dietary Fiber and the Etiology of Hormone Dependent Cancers

Cancers of the breast, endometrium, ovary, and prostate fall into the hormone-dependent classification. An association between hormonal status and cancer risk arose from observations of oestrogen deprivation and breast cancer and testosterone deprivation and prostate cancer. Nutritional influences on breast cancer have been studied extensively and several (but not all) studies show diminished risk with greater intakes of dietary fiber. The situation for other cancers, especially prostate cancer, appears to be rather unclear, but given the commonality of the proposed protective mechanisms, it is reasonable to expect that some linkage may be found. Male vegetarians have been reported to have lower testosterone and oestradiol plasma concentrations compared to omnivores, and inverse correlations of testosterone and oestradiol with fiber intake have been reported. Potential Mechanisms Indicating a Role in the Etiology of Hormone-Dependent Cancers metabolites. Direct binding of sex hormones...

Familial ovarian cancer

Ovarian cancer is the fifth most common cancer in women (excluding skin) in the USA and UK. Since the prognosis of this neoplasm is largely determined by the stage of the disease at presentation, and approximately 80 of cases have spread beyond the ovary when first diagnosed, ovarian cancer accounts for a disproportionate number of deaths compared with other cancers of the female genital tract. A family history of ovarian cancer confers the highest known risk factor for developing the disease. Other risk factors include gonadal dysgenesis (Szamborski et al., 1981), early menarche and late menopause, whereas reducing the number of ovulation events either by use of an oral contraceptive or through pregnancy reduces the risk of ovarian cancer. The oral contraceptive pill appears to offer protection against the risk of developing both sporadic and familial cancer and continues to provide protection for some years after the contraceptive has been terminated (Anonymous, 1987). Families with...

Pathology of ovarian cancers in mutation carriers

All studies performed to date indicate that carcinoma is the most common histological diagnosis observed in BRCA1- and BRCA2-associated ovarian cancer. Most of the information available on familial ovarian cancer is based on BRCA1-linked disease because, unlike familial breast cancer patients, BRCA1 germline mutations are approximately four times more common than BRCA2 mutations in ovarian cancer patients (Gayther et al., 1999 Boyd et al., 2000). All five subtypes of malignant epithelial ovarian neoplasms have occurred in BRCA1 mutation carriers. Even a case of a malignant transitional cell carcinoma - a very rare entity -has been found to occur in an individual carrying a BRCA1 mutation (Werness et al., 2000a). It is generally agreed that the frequency of endometrioid and clear-cell carcinoma occurring in BRCA1 mutation carriers is similar to that of sporadic cases (Rubin et al., 1996 Stratton et al., 1997 Aida et al., 1998 Berchuck et al., 1998 Johannsson et al., 1998 Zweemer et...

Grading and staging of familial ovarian cancers

The first report on BRCA1-associated ovarian carcinoma found that, overall, the tumours were of higher grade and higher stage than their historic age-matched controls (Rubin et al., 1996). However, grade I stage I tumours have been observed, suggesting that loss of differentiation occurs in parallel with spread of disease. These findings have been largely reproduced by a number of other groups (Aida et al., 1998). Werness et al. (2000a) and Boyd et al. (2000) also found fewer low-grade carcinomas in the mutation carriers. Zweemer et al. (1998) and Pharoah et al. (1999) found that a greater number of high-stage (III IV) cancers and fewer low-stage (I) cancers occurred in individuals with BRCA1 and BRCA2 germline mutations. Shaw et al. (1999) also studied a familial ovarian cancer group comprising BRCA1 and BRCA2 carriers and reported that they had a higher grade of cancer than their sporadic counterparts. However, Berchuck et al. (1998) found that, although the BRCA1 cases in their...

The Stages Of Initiation And Promotion In Human Carcinogenesis

Evidence for the existence of the stages of initiation and promotion in the human have come largely from clinicopathological and epidemiological studies. That initiation occurs in the human is evidenced by the spontaneous incidence of cancer in the human population, implying initiation as an essential component for the development of such neoplasms. Evidence for the existence of the stage of promotion in human neoplasia is not so definitive as that seen in the

Principles Of Cancer Treatment Curability

The logical objective of the treatment of cancer is destruction of all cancer cells. The disease is then eradicated and the patient 'clinically cured'. This definition of clinical cure is impractical as it can only be proven by a complete search for asymptomatic deposits of tumour on death. However, clinical cure should follow the complete removal of all non-invasive cancers, and also a number of small invasive cancers, particularly in superficial sites, which have not metastasized. Life is personal and freedom from recurrence of the cancer during the remainder of a patient's lifetime constitutes 'personal cure'. This does not rule out the possibility that the disease is present in asymptomatic form and is clearly dependent upon the duration of life following its diagnosis. By this definition, the patient who is killed in a road accident on the way home from hospital following the palliative resection of an incurable gastric cancer is 'cured' A third definition of cure is 'statistical...

Esophageal cancer5111214 Epidemiology

More than 99 percent of esophageal tumors are of the malignant variety. However, esophageal cancer is relatively uncommon in the United States, with an annual rate of less than 10 per 100,000. Most are diagnosed between the sixth and the eighth decade of life, and, in general, men are two to four times more likely to be afflicted than females. Nevertheless, it is a lethal problem once diagnosed, the overall 5-year survival rate is typically less than 10 percent, and it is responsible for approximately 10,000-12,000 deaths per year in the United States. Internationally, esophageal cancer is much more prevalent, accounting for greater than 300,000 new cases per year. It is endemic in certain parts of the world. For example, in northeast Iran and in parts of northern China, there are well over 100 new cases per 100,000 population each year. Furthermore, esophageal cancer has also been consistently one of the top 10 leading causes of cancer deaths worldwide. Based on epidemiologic...

Folate Deficiency And Cancer

The biochemical manifestations of a folate deficiency can be seen in a decreased supply of S-adenosylmethionine and then in loss of methylation of CpG islands as well as a decrease in dTMP and a rise in the dUMP pool, which has been shown to result in misincorporation of deoxyuridine (du) into DNA. Recently, Ames and colleagues showed the significant extent of misincorporation of dU into DNA in folate-deficient patients (9) and, like others (10), speculated on the consequences. The protective effects of adequate folate, and of genetic polymorphisms altering the composition of the intracellular folate pool, with regard to the risk of colon cancer and perhaps other carcinomas has also been recently reviewed (11,12). Recent work by James and her colleagues have also shown that cells transformed in vitro are more tumorgenic in vivo (13).

Detecting Cancer Tumors

Loss of heterozygosity (LOH) is a method of monitoring genetic deletions common in tumors for many types of cancer. LOH is manifested by severe allelic imbalance at a locus in a single-source DNA sample so that a true heterozygote almost appears as a homozygote since some of the chromosomes have a deletion present in the region of the locus being PCR-amplified. Probably the only time that LOH would have an impact on human identity testing is if an archived clinical specimen from a tissue biopsy was used as a reference sample to identify someone from a mass disaster (see Chapter 24). However, it is worth being aware of the fact that normal and cancerous tissue from an individual can vary fairly dramatically in some instances in terms of their STR allele peak heights (Vauhkonen et al. 2004). An examination of a cancer biopsy tissue specimen compared to normal tissue with the nine STR loci present in the AmpFlSTR Profiler kit found that the D13S317 locus exhibited a severe peak imbalance...

Gastrointestinal Cancers

A basic understanding of the spread of cancers of the gastrointestinal tract relies upon the depth of mural penetration. Originating in the epithelial layer, the cancer's invasion of the wall may variously extend into the lamina propria, muscularis mucosae, submucosa, muscularis propria, and subserosal connective tissue or through the serosa with or without direct invasion of adjacent structures. This determination forms the basis of the universally adopted TNM staging classification,1-3 encompassing all three prognostic factors of tumoral mural penetration (T), nodal involvement (N), and distant metastatic spread (M) in one staging system. Staging is the process by which the anatomic extent of a tumor is defined at a certain point of time. Onco-radiology has had a major influence on the TNM staging system, which has incorporated changes to accommodate the information available by the widening spectrum of diagnostic and interventional imaging and endoson-ography.4 Depth of tumor...

The Concept of Cancer An Overview

Although the biological, epidemiological, and genetic origins and indicators of cancer are vitally important they are the frontiers on which the disease is being battled cancer is more than the sum of its physical parts. It is also a socially imagined disease that is collectively thought about, embellished, and reacted to in ways that mesh with a people's established social and cultural norms. In some African countries, for example, perceptions of cancer as a stealthy, insidious disease mesh with notions of malice and witchcraft (Bezwoda et al., p. 123 El-Ghazali, p. 101). In parts of Italy cancer poses the threat of social as well as physical disruption and death, a viewpoint that meshes with the importance Italians place on defining themselves and their worth in relationship to others (Gordon). In the United States, by contrast, having cancer sometimes is considered a personal failing and responsibility, a notion that clearly draws on deeply ingrained concepts of individuality and...

Cancer and Endof Life Care

An oncologist may be asked to taper off or stop treatment at a juncture where the oncologist foresees, with statistical and collegial support, that continued treatment is still likely to benefit the patient. In equally problematic situations the reverse may occur. Crawley and her colleagues cite as an example an African-American man with metastatic colon cancer who angrily rejected his physician's suggestion that they had reached a point where the interventions would be costly and would serve only to prolong the man's suffering (Crawley et al., pp. 673-675). The patient demanded that he receive every medical test and procedure available regardless of the cost. This insistence, the physician felt, was based on the man's inability to grasp the limitations of the technological options still available to him. The provision of good end-of-life care for cancer patients frequently is complicated by disagreements, poor communication, and cultural differences. However, there are strategies...

Cancer Care and the Future

Future developments in cancer care will be affected by advances in the clinical control and prevention of the disease. Ongoing genetic and molecular research promises not just more effective treatments for cancer but also less invasive procedures for patients, greater patient autonomy, and improved quality of life. Potential problems may include a compounding of concerns about informed consent for cancer clinical trials and genetic susceptibility testing, as well as more macro issues such as the inequitable distribution of cancer care resources in the United States and globally. Also, current trends suggest continued growth in informal cancer care resources ranging from online information networks to holistic alternatives to conventional cancer care. Many of these resources have the potential for linking together and empowering cancer patients but also of misinforming them or undermining the oncologist's authority and purpose through the exposure of patients to multiple, conflicting...

Primary care in the cancer genetics service for Wales

Guidelines were drawn up and distributed to all GPs in Wales by the National Assembly for Wales (Box 9.1). Crucially, the guidelines were developed in a multidisciplinary fashion - initially in conjunction with the cancer lead clinicians, public health representatives, voluntary groups, patient groups and GPs. Multiple meetings were required over an 18-month period and all decisions were taken to and endorsed by the Royal College of General Practitioners, the GP committee of the BMA, and the appropriate government committees. Key to our work with the GPs was a series of focus groups, as outlined in Box 9.2, giving a real sense of ownership to the primary care groups. Setting up a cancer genetics service Referral guidelines Breast cancer 1 first-degree relative with male breast cancer A first-degree relative with bilateral breast cancer Note breast cancer can also be inherited through the paternal side of the family Breast ovarian cancer Minimum 1 of each cancer in first-degree...

Molecular Genetics Of Colon Cancer

Colorectal cancer is a well-defined clinical model for studying the molecular events of tumor development and progression. There is a linear progression, during which the neoplasm develops from hyperplastic epithelium in aberrant crypt foci through adenoma to carcinoma and metastasis (28). This sequence reflects the accumulation of specific genetic alterations. It is thought that five to seven genes must be altered sequentially in order for cancer to develop (10). Two separate sequences of molecular pathogenesis have been postulated for colorectal cancer, based upon observations in families with inherited predisposition to colorectal cancer (Fig. 1). The first model is derived from observations initially made in patients with FAP. Family members with this condition (which accounts for 1-2 of colorectal cancer) inherit an inactivating mutation in the adenomatous polyposis coli (APC) gene. Inactivation of the second allele (occurring in about 1 of 106 colorectal epithelial stem cells)...

Immune function and cancer

The diet is believed to play an important role in the onset of carcinogenesis, and there are a number of carcinogens present in food, including mycotoxins, polycyclic hydrocarbons, and pesticides. Associations have been made between dietary fat intake and morbidity and mortality from breast and colon cancer. Another possible mechanism for the proposed protective effects against cancer of olive oil compared with sunflower oil involves diet-induced alterations in host immune responses. Both the type and concentration of dietary fats have been reported to influence immune status in several animal models. The PUFA C18 2 is necessary for T-cell-mediated immunity, but high intakes will suppress immune function and may therefore increase the risk of cancer. Furthermore, comparisons between the effects of diets rich in C18 2 and those rich in C18 1 on varying indicators of immune function in mice have shown that, while dietary C18 2 predisposed animals to suppression of certain...

Triggering immune reaction against cancers

A number of antigens encoded by genes of the MAGE, BAGE and GAGE families can be recognized by cytotoxic T lymphocytes (CTLs) in a wide range of tumors. These antigens are not expressed in normal tissues and are presented to the T cell receptor in the context of HLA. Other tumor antigens result from mutations or recombinations of ubiquitous genes such as p53, HLA-A2 or CASP-8. One can hypothesize that different or increased presentation of these antigens by the tumor cells themselves, or by antigen-presenting cells (APCs) such as monocytes-macrophages or dendritic cells can activate the immune reaction directed against cancer cells. Thus, increased immunogenicity of tumor cells has been monitored through a direct pulse of antigenic peptides or transfer of sequences coding for target antigens into tumor cells or into APCs. This approach parallels DNA vaccine models dedicated to infectious diseases.

Classification of Cancer Types

The term cancer is general, in that it represents a large group of related diseases that arise from neoplasms. A neoplasm is classified by the type of tissue in which it arises and the stage to which it has progressed. Neoplasms are also called tumors. Not all tumors are cancerous. A tumor that grows in one place and does not invade surrounding tissue is called benign. In contrast, invasive tumors are called malignant. These are cancerous. ESTIMATED NEW CANCER CASES AND DEATHS IN THE UNITED STATES 2000 ESTIMATED NEW CANCER CASES AND DEATHS IN THE UNITED STATES 2000 *(the American Cancer Society's Clinical Oncology, Lenhard R.E., Osteen R.T., Gansler T., 2001) *(the American Cancer Society's Clinical Oncology, Lenhard R.E., Osteen R.T., Gansler T., 2001) Estimated new cancer cases and deaths in the United States in 2000. Adapted from Lenherd, 2001.

Development of benchmarks for the regional cancer genetics service

Box 9.3 Benchmarks being piloted for cancer genetics service provision EQ Cancer genetics clinics per million EQ A Referrals per million cancer type A Proportion of referrals getting a clinic appointment with a counsellor at a cancer genetics clinic EF Numbers seen in clinic (e.g. cancer genetics clinic) Talks given per month (total) (counsellor cancer genetics clinic)

Cancer Metastatic to the Skin

Metastases to the skin from an internal neoplasia are rare (236). Reported incidence varies from 0.7 to 9 but the most realistic figure is approximately 1.3 . Skin involvement as the presenting sign of visceral cancer is even less frequent, occurring in 0.8 of cases. In general, a metastatic event must be viewed as a multistep process that involves detachment from the primary site, intravasation (penetration to blood lymphatic vessels), circulation (survival of cells by homotypic aggregation), stasis, and extravasation with tissue invasion. The biological basis for site-specific metastases is complex and not well understood, but the following factors may be involved cellular adhesion molecules, ability to invade tissue by producing proteases, and ability of tumor cells to induce angiogenesis.

Long Term Regular Exercise Lowers the Risk of Sex Hormone Sensitive Cancers

A study of 5398 college graduates ages 20-80 years, of whom 2622 were former athletes and 2776 were nonathletes, showed that the former athletes had a significantly lower lifetime occurrence of breast cancer and cancers of the reproductive system compared to the nonathletes. More than 82.4 of the former college athletes began their training in high school or earlier, compared to 24.9 of the nonathletes. The analysis controlled for potential confounding factors, including age, age of menarche, age of first birth, smoking, and cancer family history. The relative risk (RR) for nonathletes compared to athletes for cancers of the reproductive system was 2.53 (95 confidence limit (CL), 1.17-5.47) (Figure 5). The RR for breast cancer was 1.86 (95 CL, 1.00-3.47). The former college athletes were leaner in every age group compared to the nonathletes.

Carcinogen Classification In Relation To The Natural History Of Neoplastic Development

With the division of the process of carcinogenesis into at least three distinct and sequential stages, it now becomes possible to place carcinogenic agents into various categories depending on their effecting one or more of the stages of initiation, promotion, and progression. Such a classification is given in Table 9.10. Agents that are capable of initiation and thus are true incomplete carcinogens are very rare if they exist at all. The pure initiating activity of certain chemicals in specific tissues has been reported (cf. DiGiovanni, 1992) but in most instances, at higher doses or in different tissues, such agents can be shown to be carcinogenic, usually acting as complete carcinogens. On the other hand, as we have seen from the experimental basis for a distinction between initiation and promotion, very low doses of complete carcinogens will act to initiate cells but cannot sustain the remainder of the carcinogenic process. This consideration is undoubtedly very important in...

And Epidemiology Of Prostate Cancer

The vast majority of malignant tumors of the prostate are epithelial and termed adenocarcinomas. The prostate normally has several types of epithelial cells. Basal cells are located between the luminal cells and the basement membrane and form a continuous layer in the non-neoplastic gland. This cell layer may also contain a stem cell compartment that differentiates into luminal cells. Neuroendocrine cells are androgen-independent cells dispersed throughout the basal layer and are believed to provide paracrine signals that support the growth and function of luminal cells. The luminal cells are androgen-dependent and produce prostatic secretory proteins. Prostate adenocarcinomas have features of both basal and luminal cells, raising controversy as to the cell of origin (4). A likely possibility is that most cancers are derived from the ill-defined stem cell compartment. The prostate develops through budding of epithelium from the urogenital sinus into the surrounding mesenchyme....

Cancer Patients Psychotherapy

As treatment for cancer has become more effective, it is better thought of as a chronic rather than a terminal illness. However, given the progressive nature of the disease, and the fact that approximately half of all people diagnosed with cancer will eventually die of it, a readjustment in the medical approach to cancer is needed. Currently, we focus almost exclusively on cure, despite the fact that cure is often impossible. We pay far less attention to care, the process of helping ill people live with cancer as well and as long as possible. That latter perspective is the focus of this article. Psychotherapy, especially in groups, can provide a new social network with the common bond of facing similar problems. Just at a time when the illness make a person feel removed from the flow of life, when many others withdraw out of awkwardness or fear, psy-chotherapeutic support provides a new and important social connection. Indeed, the very thing that damages other social relationships is...

Immune response to a cancer

There is some evidence that cancer cells have surface membrane antigens called tumour-specific antigens (TSA) or tumour-associated antigens (TAA) that are recognized by the immune system as non-self, and can elicit an immune response. Antibodies secreted by B-lymphocytes will coat tumour cells and with the help of complement and phagocytic cells can cause tumour cell destruction. CD8+ T-lymphocytes and NK cells can cause direct tumour cell killing, whereas CD4+ T-cells release cytokines to augment tumour cell killing by macrophages. The concept of immune surveillance as protection against cancer, whereby lymphocytes continuously check dividing cells for mutations and destroy unacceptable cells, has not been proved (Fig. 11.15).

Immunodeficiency and cancer

Immunocompromised individuals such as patients after radiotherapy or chemotherapy, transplant patients on immunosuppressive drugs or those with an AIDS are at an increased risk of developing cancer. The risk is particularly for lymphoproliferative and cutaneous malignancies, which Figure 11.15. Histological slide of a patient with cancer of the breast. Note the infiltration of lymphocytes both into the connective tissue surrounding the cancer as well as directly into the cancer itself. Figure 11.15. Histological slide of a patient with cancer of the breast. Note the infiltration of lymphocytes both into the connective tissue surrounding the cancer as well as directly into the cancer itself.

Immunodiagnosis of cancer

If tumour cells express surface membrane, cytoplasmic or secreted products of specific antigenicity and in sufficient quantities, it should be possible to detect these by developing monoclonal antibodies against them. Unfortunately these techniques have not yet reached widespread application in either screening for early cancer or follow-up of cancer. The three most commonly used antigens used for these purposes are prostatic-specific antigen (PSA), used for screening and follow-up of prostate cancer carcin-oembryonic antigen (CEA), used for follow-up of colon cancer and a-fetoprotein, used for diagnosis and follow-up of liver cancer.

Immunotherapy of cancer

Numerous attempts have been made to employ immuno-logical methods to treat cancer, but none have been very successful. The different techniques can be grouped together as active, passive and adoptive immunotherapy. Active immunotherapy refers to those techniques designed to enhance components of the immune system most likely responsible for antitumour activity. Bacillus Calmette-Guerin (BCG) has been used to enhance cellular immunity, particularly macrophage function, and various cytokines such as IFN, IL-1, IL-2, IL-4, IL-12 and TNF are being tested to enhance immune function. Passive immunotherapy usually refers to the use of monoclonal antibodies directed against TSA in an attempt to destroy the tumour cell. Adoptive immunotherapy refers to the transfer of immune components such as macrophages and NK cells from one individual to another. The most extensively studied in this group are known as lymphokine-activated killer (LAK) cells.

Results Of Gene Expression Analysis Of Prostate Cancer

The subset of genes expressed in normal and neoplastic prostate tissue has been estimated based on theoretical and practical considerations. These studies are beginning to define the prostate cancer transcriptome and a possible role for some genes in critical processes. The Cancer Genome Anatomy Project (CGAP) of the National Cancer Institute was designed to identify genes responsible for cancer by sequencing of cDNA clones representing RNA from normal, precancerous, and malignant cells (http cgap.nci.nih.gov ). Currently, there are 17,040 genes identified in the 139,041 ESTs from prostate libraries listed in CGAP. These resources have been combined with independent data to identify 15,953 prostate-specific EST clusters in the prostate expression database (http www.pedb.org ) (37). This is believed to represent about 50-75 of the prostate transcriptome. An additional estimate, based on combining publicly available SAGE data, predicted 37,000 genes in the prostate transcriptome (38)....

High Intensity Focused Ultrasound HIFU for the Treatment of Localized Prostate Cancer

We evaluated 85 patients with localized prostate cancer treated with high-intensity focused ultrasound (HIFU) for biochemical disease-free rate, safety, morbidity, and predictors of biochemical outcome. A total of 85 patients underwent HIFU with the use of Sonablate and with at least 12 months of follow-up. The median age was 70 years (range, 54 to 86 years), and the median preoperative prostate-specific antigen (PSA) level was 10.9ng ml (range, 3.39 to 89.6). The median length of follow-up was 20 months (range, 6 to 56). Biochemical failure was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. Biochemical failure developed in 27 (23 85) of the patients. The biochemical disease-free survival rates at 3 years for patients with pretreatment PSA less than 10ng ml, 10.01 to 20.0ng ml, 20.01 to 30.0ng ml,and more than 30.0ng ml were 97 ,75 , 33 , and 0 , respectively. Final follow-up sextant biopsies...

Carcinogenicity in Animals

AFB1 is a potent liver carcinogen in many species of animals, including rodents, nonhuman primates, and fish. In appropriate circumstances, dependent on such variables as animal species and strain, dose, route of administration, and dietary factors, significant incidences of tumors have been induced at sites other than the liver, such as kidney and colon. AFB1 has been demonstrated to induce liver tumors in two species of lower primates the tree shrew (Tupaia glis) and the marmoset (Sagui-nus oedipomidas). All liver tumors of the tree shrew were classified as hepatocellular carcinoma (HCC) and developed in a manner similar to those of the rat. Unlike the case with rats, in the marmoset histologic observation revealed the association of cirrhotic changes with liver tumor development. Rhesus monkeys have also proven to be susceptible to AFB1 carcinogenicity. Data from 47 monkeys, representing three species (rhesus, cynomolgus, and African green), that had received AFB1 have been...

Identification of individuals with a genetic predisposition to cancer

The basic aims of genetic management for breast and ovarian cancer risks are To identify individuals who are at a significantly increased genetic risk of inherited cancer To provide advice and counselling to individuals about their risks of developing cancer To provide patients affected with cancer that is associated with a genetic predisposition with appropriate genetic counselling and management Given the growing awareness and demand for advice on familial aspects of cancer and the limited resources available to meet this demand, primary care and breast clinics should be provided with guidelines to resolve enquiries relating to inherited aspects of common cancers. The specialist services should be reserved for known familial forms of the more common cancers (only a minority of the total caseload), for other high-risk situations, and for cases where primary care professionals themselves consider specialist referrals to be desirable (Emery et al., 1999a). The main roles of primary...

Cell Cycle and Cancer

Cavenee, W.K. & White, R.L. (1995) The genetic basis of cancer. Sci. Am. 272 (March), 72-79. Chau, B.N. & Wang, J.Y.J. (2003) Coordinated regulation of life and death by RB. Nat. Rev. Cancer 3, 130-138. Fearon, E.R. (1997) Human cancer syndromes clues to the origin and nature of cancer. Science 278, 1043-1050. Intermediate-level review of the role of inherited mutations in the development of cancer. Kinzler, K.W. & Vogelstein, B. (1996) Lessons from hereditary colorectal cancer. Cell 87, 159-170. Evidence for multistep processes in the development of cancer. Intermediate coverage of the function of protein p53 in the normal cell cycle and in cancer. C. (2003) The significance of unstable chromosomes in colorectal cancer. Nat. Rev. Cancer 3, 695-701. Sherr, C.J. & McCormick, F. (2002) The RB and p53 pathways in cancer. Cancer Cell 2, 102-112. Weinberg, R.A. (1996) How cancer arises. Sci. Am. 275 (September), 62-70. Yamasaki, L. (2003) Role of the RB tumor suppressor in...

Deregulation and Cancer

Deregulation of cell cycle control proteins plays a key role in the development of cancer. Overactivation of proteins that favor cell cycle progression, namely cyclins and CDKs, and the inactivation of proteins that impede cell cycle progression, such as CKIs, can result in uncontrolled cell proliferation. In human tumors, it is genes encoding the proteins that control the transition from the G1 to the S phase that are most commonly altered. These genes include those for cyclins, CKIs, and pRb. Such mutations overcome the inhibitory effects of pRb on the cell cycle, causing cells to have a growth advantage. In some cancers, this occurs after the direct mutation of the pRb gene, resulting in the protein's loss of function. In a larger set of cancers, pRb is indirectly inactivated by the hyper-activation of CDKs. This may result from over expression of cyclins, from an activating mutation in CDK4, or from inactivation of CKIs. There is much evidence to suggest that cyclins can act as...

Guidelines for risk estimation in individuals with a family history of cancer

Calculation of risk of breast cancer In families where there is no clear-cut Mendelian genetic predisposition, empirical risks for breast cancer may be calculated based on the age at diagnosis of breast Table 11.1. Importance of genetic predisposition to breast cancer Table 11.1. Importance of genetic predisposition to breast cancer Age at onset of cancer (years) cancer in first-degree relatives in studies carried out by Houlston et al. (1991) in the UK and by Claus et al. (1996) in the USA. Where more than one relative is affected various studies have produced figures for the relative risks to individuals (Table 11.1 Murday, 1994). For the majority of individuals with a family history of cancer, no specific gene mutations will have been identified as being causative. In such cases, data from epidemiological studies must be used to calculate the risks to relatives of those affected with cancer. Where a single relative is affected with breast cancer, data from the Claus et al. (1996)...

Clinical Features In Hereditary Breast And Ovarian Cancer Syndrome

BRCA mutations occur in approximately 20 of families with inherited susceptibility to breast cancer. Personal and family characteristics associated with an increased likelihood that a BRCA mutation will be identified are listed in Table 3. Breast cancers in BRCA1 carriers often have medullary features, are more likely to be poorly differentiated with high mitotic rates and S-phase fraction, lack an in situ component, have low estrogen and progesterone receptors score, and node-positive. BRCA2 tumors are more histologically heterogeneous and more likely to be estrogen-receptor-positive. For BRCA1 carriers, breast cancer survival rates are similar to those for sporadic cancer patients when controlling for stage. The lifetime risk for second primary breast cancers in BRCA-mutation carriers with breast cancer is 40-60 , with 5-year risk estimates of 22-31 . The lifetime risk for male breast cancer in BRCA2-mu-tation carriers has been reported to be approximately 6.3 . 1 The average age of...

Screening In Hereditary Breast And Ovarian Cancer Syndrome

Although overall population screening reduces breast cancer mortality by 25-40 in women between the ages of 50 and 70 years, no data are available on the outcomes of interventions to reduce risk in HBOC syndrome. No data are available to demonstrate that surveillance for ovarian cancer in high-risk women reduces mortality 3 because transvaginal ultrasound and CA-125 lack sensitivity and specificity. However, recommended screening in BRCA gene mutation carriers includes monthly breast self-examination starting at age 18, semiannual clinical breast examination and annual mammography starting at age 25, and starting at age 30-40, semiannual transvaginal ultrasound with color Doppler, serum CA-125, and pelvic examination. Several studies have shown that in women with germline BRCA1 and BRCA2 mutations, breast cancers are likely to occur as interval cancers 4 and that standard mammography is more likely to be negative than in women at low or moderate risk. 5 Recent data suggest that...

Chemoprevention In Hereditary Breast And Ovarian Cancer Syndrome

Women who desire risk reduction intervention for breast cancer have the option of chemoprevention with tamoxifen therapy (20 mg day for 5 years) or prophylactic surgery. The National Surgical Adjuvant Breast and Bowel Project prevention trial in healthy women 35 years and older with a 1.7 or greater cumulative 5-year risk for developing breast cancer demonstrated short-term reduction in risk of developing estrogen-receptor-positive breast cancer by 49 . The utility of tamoxifen for breast cancer risk reduction in women under the age of 35 years is unknown and current evidence-based data regarding tamoxifen breast cancer risk reduction in BRCA gene mutation carriers are insufficient. Women with BRCA1 mutations who develop breast cancer have estrogen-receptor-negative tumors in approximately 80 of cases, whereas women with BRCA2 mutations who develop breast cancer have estrogen-receptor-positive tumors in 80 of cases. Therefore, the use of tamoxifen for breast cancer prevention in...

Environmental Factors in the Etiology of Human Cancer Chemical Agents and Processes

As noted in Chapter 1, the incidence of cancer at various tissue sites in humans varies greatly among countries and even within certain countries. Immigrants and especially their descendants tend to acquire the cancer incidences characteristic of their new habitats. The conclusion has been drawn that a high percentage, perhaps as much as 80 , of the more frequent and statistically important human neoplasms (of the bronchi, stomach, colon, breast, and others) have environmental factors, including lifestyle, as major components of their etiology. This has further led to a general agreement that at least 50 of all human cancers could be avoided if existing etiological knowledge were applied (cf. Tomatis et al., 1997). Differences in the exposure to carcinogenic radiations other than solar ultraviolet (UV) light as the major cause of skin cancer , infectious disease, or hormonal factors do not appear sufficient to explain the geographical differences noted for most of the major cancers....

Chemical Carcinogenesis In Humans

In Chapter 3 the experimental basis for the induction of cancer by chemicals of both exogenous and endogenous origin was considered. In a general sense, our knowledge of chemical carcino-genesis in the human can be traced to the observation by Ramazzini (cf. Wright, 1964) of the relatively high incidence of breast cancer in Catholic nuns (Chapter 1). Ramazzini proposed that breast cancer in this occupational group was the result of their lifestyle, and today there is good evidence to argue that endogenous hormonal interactions play a dominant role in the incidence of breast cancer, especially as related to the time of childbearing (Henderson et al., 1982). The first evidence for an exogenous chemical cause of cancer was described by Hill, who related the use of tobacco snuff to the occurrence of nasal polyps (Hill, 1761). Somewhat later, Pott demonstrated the causal relationship of soot to scrotal cancer in chimney sweeps (Chapter 3). Within the last century, a number of specific...

Breast Cancer and Angiogenesis

In solid tumours, growth beyond a millimetre cannot occur without vascular support (Folkman 1996). Transgenic animal tumour model experiments have shown that progression from an in-situ to invasive cancer is accompanied by the onset of angiogenesis (Rak et al. 1995). There are a number of clinical examples where vascularization has been related to tumour progression (e.g., in the change from breast ductal carcinoma in-situ to invasive cancer (Gilles et al. 1995) Bose et al. 1996). Immunohistochemical techniques show changes consistent with this observation for example, expression of the endothelial cell-specific tyrosine kinase receptor, Tie-2 (TEK) is increased during the transition from benign to invasive breast cancer (Bernsen et al. 1998). The most potent pro-angiogenic factor in breast tumours is vascular endothelial growth factor (VEGF), initially termed vascular permeability factor due to its hyperpermeable effect on vessels (Senger et al. 1983). VEGF leads to endothelial cell...

Laparoscopy and Gastric Cancer Perspectives and Controversies

Laparoscopic Approach to Gastric Laparoscopic Staging of Gastric 114 The laparoscopic surgery revolution has resulted from the development of new techniques and technologies which allow the performance of increasingly complex procedures. While gastric resection for cancer has not been embraced with such enthusiasm as removal of other abdominal viscera, this may be a reflection of the relative rarity of this disease in the West. However, a number of groups have undertaken subtotal or total gastrectomy, albeit in small series of patients. Goh et al1 surveyed advanced laparoscopic surgeons and identified a total of 118 laparoscopic gastrectomies performed prior to November 1994. In 46 (38 ) of these cases, the indication for surgery was gastric cancer. This report included our early cases and established the feasibility of laparoscopic gastrectomy. This chapter outlines our appraisal of the current role of laparoscopy both diagnostic and therapeutic in the management of gastric cancer....

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

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