The Association Of NAT1 And UGT2B7 Gene Polymorphisms With The Susceptibility To Bladder Cancer In Benzidine Exposed Chinese Workers.

In order to explore the possible association of the gene polymorphisms of NAT1 and UGT2B7 with elevated risk to bladder cancer among benzidine exposed Chinese workers, two polymorphic gene, N-Acetyltransferase 1 (NAT1) and UDP-glucuronosyltransferase2B7(UGT2B7)were genotyped in a member of benzidine-exposed cohort in Shanghai dye industry and a group of normal residents of the same city. A polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) based procedure was employed.The results showed that the variant NAT1 genotypes (totally 16 different genotypes were found) and the combination of loci corresponding to three different phenotypes (enhanced, wild and decreased) were found equally distributed among different Papanicolaus' grading groups(Pap≤ II, II< Pap < III, and Pap≥III , P>0.05). Compared with Pap ≤II group, no significant overrepresentations of allele NAT1*10 which code for a enzyme protein isoform with enhanced catalyzing activity were found in the II< Pap < III group[P=0.43,OR1.29, 95%CI(0.77,1.84)] and in the Pap ≥III group [P=0.54,OR1.17, 95%CI(0.71,1.92)]. The allele of NAT1*14A represented more in the Pap ≤II group than in II< Pap < III group [P=0.03, OR 0.21, 95%CI (0.04,0.99)], however, no significant difference was observed between Pap ≤II group and Pap ≥III group [P=0.15,OR 0.34, 95%CI(0.07,1.60)]. Stratified analyses were made with individuals' smoking hsabits, benzidine occupation exposure level. However, no significant differences of variant NAT1 genotypes distribution were observed during the stratification. Significant overpresentation of mutation allele of of UGT2B7 C802T (H268Y) was found in a group of benzidine exposed bladder cancer patients, compared with benzidine exposed non-diseasd individuals and normal population in the same city, respectively. The homozygous mutation genotype UGT2B7(T/T) displayed in higher frequency in benzidine exposed bladder cancer patients than in normal population in the same city [P=0.006, OR3.30,95%CI(1.36-7.98) ]. The data suggested that the mutation allele of UGT2B7 could affect individual's susceptibility to bladder cancer in the case of benzidine occupational exposure. The significant difference of UGT2B7 polymorphism between normal Chinese and Caucasian population was also witnessed In conclusion, the representation of UGT2B7 polymorphism between Chinese and Caucasian displayed significant racial differences. The population distribution of various polymorphic isoforms of NAT1 displayed no association with premalignant cellular alteration of exfoliated urothelial cells in benzidine exposed Chinese workers. Combined phenotype analysis of NAT1 and NAT2 also revealed that no significantly statistic differences of variant phenotypes of NAT1 and NAT2 in different Pap test level groups were found. However, the mutated isoform of UGT2B7 was a risk factor for developing bladder cancer in benzidine exposed Chinese workers.