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Exon 3 polymorphisms and haplotypes of O6-methylguanine-DNA methyltransferase and risk of bladder cancer in southern China:a case-control analysis

Exon 3 polymorphisms and haplotypes of O6-methylguanine-DNA ...

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第四届全国环境与职业医学研究生学术研讨会

作者： Chunping Li, Jia Liu, Aiping Li, Lixin Qian, Xinru Wang, Qingyi Wei, Jianwei Zhou, MD,PhD Zhengdong Zhang MD,PhD Department of Molecular Cell Biology and Toxicology, Jiangsu Provincial Key Laboratories of Human Functional Genomics and of Applied Toxicology School of Public Health, Nanjing Medical University, Nanjing 210029, People’s Republic of China Department of Urological Surgery, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA

Methylating agents are involved in bladder carcinogenesis. O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein that removes methyl group from O6-methylguanine and thus plays an important role in the etiology of cancer. We hypothesized that two MGMT polymorphisms in exon 3, C16195T (or MGMT L53L) and C16286T (or MGMT L84F), are associated with risk of bladder cancer. In a hospital-based case-control study of 167 patients with bladder cancer and 204 cancer-free controls frequency-matched by age, sex, smoking status, and alcohol use, we genotyped these two MGMT polymorphisms. We found that these two polymorphisms alone had a nonsignificant main effect on risk of bladder cancer. However, when these two polymorphisms were evaluated together, individuals with the combined genotypes or haplotypes with one or more variant alleles (i.e., the 16195T and 16286T alleles) had statistically significantly increased risk of bladder cancer (adjusted odd ratio [OR] = 1.67, 95% confidence interval [CI], 1.01-2.77) compared with those with no variant allele. In the stratification analysis, the risk of bladder cancer was increased in a dose-response manner as the age increased (Ptrend - 0.010), and the increased risk was more pronounced among old subjects (> 65 years) (adjusted OR = 2.51, 95% CI, 1.05-6.04), men (1.76, 1.00-3.10), and non-drinkers (1.91, 1.08-3.36). In conclusion, these two MGMT polymorphisms may jointly play a role in the etiology of bladder cancer in southern chinese population. Larger studies are warranted to validate our findings.

关键词： MGMT Polymorphism Bladder cancer Genetic susceptibility Molecular epidemiology southern chinese

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