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

Li, Chunping; Liu, Jia; Li, Aiping; Qian, Lixin; Wang, Xinru; Wei, Qingyi; Zhou, Jianwei; Zhang, Zhengdong

doi:10.1016/j.canlet.2005.03.043

« Previous Next »Cancer Letters
Volume 227, Issue 1 , Pages 49-57, 8 September 2005

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

Chunping Li
- 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
Jia Liu
- 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
Aiping Li
- 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
Lixin Qian
- Department of Urological Surgery, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, People's Republic of China
Xinru Wang
- 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
Qingyi Wei
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Jianwei Zhou
- 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
- Corresponding authors. Tel.: +86 25 8686 2961; fax: +86 25 8652 7613.
Zhengdong Zhang
- 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
- Corresponding authors. Tel.: +86 25 8686 2961; fax: +86 25 8652 7613.

Received 11 January 2005; received in revised form 25 March 2005; accepted 28 March 2005.

Abstract

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 non-significant 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 (P_trend=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.

Keywords: MGMT, Polymorphism, Bladder cancer, Genetic susceptibility, Molecular epidemiology, Southern Chinese

Abbreviations: MGMT, O⁶-Methylguanine-DNA methyltransferase, OR, odds ratio, CI, confidence interval