Polymorphism Of Xenobiotic Metabolism Enzyme Genes And Their Association With Susceptibility Of Occupational Bladder Cancer In Shanghai Population

Many xenobiotic metabolism enzyme (XME) genes display wide ranges of genetic polymorphism. The genetic polymorphism of these enzymes modulate individual susceptibility to certain disease. There are notable deviations on the population frequency of XME gene polymorphism among different ethnic groups and regional resident population. Analyses on the allele frequency of the polymorphic enzymes in Chinese population and further study on possible association with risk of developing diseases connecting with exposure to certain chemicals can provide necessary knowledge of genetic background of XME genes in Chinese population. Furthermore, it will help in elucidating the mechanisms of elevated risk of certain diseases connected to xenobiotic exposure and inspire a clue for development of individualization of therapy and for a better occupational medical protection practice.Benzidine, a human bladder cancer carcinogen, had been used in the dyestuff industries in Shanghai for about 30 years. There are about 400 members of a cohort of benzidine-exposed workers established in 1984 in Shanghai are still alive. The analyses were done on the association between the average Papanicolaou's gradings (APG) among 319 non-diseased subjects that participated annual surveillance and 29diagnosed benzidine occupational exposed bladder cancer patients and smoke, exposure level, age and gender. The results indicate that the smokers, former workers of the high exposure level, the older persons and males have higher APG. It reveals they are at risk of developing pre-malignant cellular alteration of urinary bladder cells and of bladder cancer. Glutathione S-transferases catalyze the conjugation of GSH to electrophilic center in xenobiotics or their metabolites. Glutathione S-transferase T1, M1 and P1 genes display polymorphism. PCR-based procedures were used to identify homozygous deletion of GSTT1 and GSTM1 genes and two polymorphic loci (A1578G, C2293T) in GSTP1 gene. Based on the previous work in this laboratory, distribution frequency of GSTT1 and GSTM1 genotypes in benzidine-exposed cohort were analyzed and their association with APG were studied. There were significant lower GSTT1 null genotype frequencies among individuals with APG(II than those with APGthat of some Caucasian population. The group of bladder cancer patients who never have any occupational exposure record to benzidine and other aromatic amine has similar 1578G allele frequency presentation, compared with normal subjects (P=0.91, OR=0.96, 95%CI 0.44-2.09), nevertheless, the group with confirmed exposure record has an elevated frequency,though the statistic significance was not reached (P=0.09, OR=1.96, 95%CI (0.89-4.32). The 1578G allele carriers in the occupational bladder cancer patients are much profound than in the group of subjects with APG lower than II (P=0.007, OR=2.90, 95%CI 1.31-6.43). The same profounding were observed in the subgroups of smokers, persons older than 60, males, and subjects of high exposure (all P value less than 0.05). Thus, 1578G allele might play a role in an association with increasing risk of...