Tobacco Related Diseases

GSTM1 and GSTT1 have been particularly studied as risk candidates for tobacco-related cancers.[14,15] While some studies show significantly increased risk for GSTM1*0 and GSTT1*0 homozygotes, others have not replicated these findings prompting the use of meta-analysis. For example, analysis using 43 studies indicates that GSTM1 null is not associated with increased lung cancer risk and that there is no evidence for an interactive effect between the genotype and tobacco consumption.1-15-1 Analysis of 31 studies of the influence of GSTM1, GSTT1, and GSTP1 polymorphisms on head/neck cancer risk found modest associations (odds ratio about 1.30) between risk and GSTM1 null and GSTT1 null with greater risk (odds ratio 2.06) associated with combinations of the genotypes.[14] Analysis of six studies also failed to identify significant associations between GSTM1 null and colorectal cancer risk.[16]

Overall, therefore, the concept that GST polymorphisms, by reflecting a detoxication-deficient phenotype,

Table 1 Glutathione S-transferase polymorphisms

Class Chromosome Genes Alleles

Alpha 6pl2 A1-A5 Al* A

Mu lpl3.3 M1-M5 M1*A

Pi llql3 PI P1*A

Theta 22qll T1-T2 T1*A

Nucleotide change

Amino acid change

Functional consequence

— 69 T Promoter 335C, 629A Thrll2, Glu210 335G, 629C Serll2, Ala210

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