IDENTIFICATION OF GENETIC POLYMORPHISMS AT THE GLUTATHIONE-S-TRANSFERASE-PI LOCUS AND ASSOCIATION WITH SUSCEPTIBILITY TO BLADDER, TESTICULAR AND PROSTATE-CANCER

Two variant glutathione S-transferase cDNAs have been described at the GSTP1 locus, which differ by a single base pair (A-G) substitution at nucleotide 313 of the GSTP1 cDNA. This results in an amino acid subst itution which alters the function of the enzyme, In this study, a nove l PCR assay has been developed which demonstrates that these two varia nt cDNAs represent distinct GSTP1 alleles (GSTP1a and GSTP1b), In a st udy of individuals with different forms of cancer, the GSTP1b allele i s found to be strongly associated with bladder cancer and testicular c ancer, In controls 6.5% of individuals were homozygous for the GSTP1b allele, In bladder cancer cases, this rose to 19.7% [n = 71, odds rati o 3.6 (1.4-9.2), P = 0.006] and in testicular cancer to 18.7% [n = 155 , odds ratio 3.3 (1.5-7.7), P = 0.002], In addition, in prostate cance r a highly significant decrease in the frequency of the GSTP1a homozyg otes was observed [control 51.0% versus 27.8% cancer cases, n = 36, od ds ratio 0.4 (0.02-3.3), P = 0.008], Increases in the frequency of GST P1b homozygotes was also observed in lung cancer and chronic obstructi ve pulmonary disease, However, these were not statistically significan t, No change in breast or colon cancer allele frequencies was observed .