Carcinogenesis Advance Access published online on June 1, 2005
Carcinogenesis, doi:10.1093/carcin/bgi143
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1 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, China
* To whom correspondence should be addressed. Fruits and certain vegetables have a protective effect on gastric cancer (GC) and folate is one of the nutrients in fruits and vegetables. We hypothesized that the polymorphisms of thymidylate synthase (TYMS) gene involved in folate metabolism are associated with GC risk. In a population-based case-control study of 337 GC cases and 326 controls, frequency-matched by age, sex, and residential areas in a Southern Chinese population, we genotyped the 28-bp tandem repeat in the TYMS 5'-untranslated enhanced region (TSER) and the 6-bp deletion/insertion at bp 1494 in the TYMS 3'-untranslated region (TS3'UTR). We found that although the TSER polymorphism had no main effect on GC risk, the TS3'UTR 6bp/6bp genotype was associated with a significantly increased risk of GC [adjusted odds ratio (OR) = 1.96, 95% confidence interval (CI) = 1.18-3.25], especially the noncardiac gastric cancer (2.16, 1.22-3.82), compared with the 0bp/0bp genotype. However, when we evaluated these two polymorphisms together and used the combined genotype with zero variant alleles (TSER 2R and TS3'UTR 6bp variant alleles) as the reference, we found that the combined genotype with three or four variant alleles was associated with a significantly increased risk of GC (2.06, 1.12-3.79), especially the noncardiac gastric cancer (2.33, 1.19-4.59), and this significant association was more pronounced among older women (> 60 years old), nonsmokers, and never tea drinkers. In conclusion, the TYMS polymorphisms, especially the TS3'UTR polymorphism, are associated with GC risk, especially the noncardiac gastric cancer, and the TSER 2R and TS3'UTR 6bp alleles might jointly play a role in the etiology of GC in the Southern Chinese population. Larger studies are warranted to verify these findings.
Received February 4, 2005
Revised May 9, 2005
Accepted May 24, 2005
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Polymorphisms of thymidylate synthase in the 5'- and 3'-untranslated regions associated with risk of gastric cancer in South China: a case-control analysis
2 Yangzhong Cancer Research Institute, Yang-Zhong City, Jiangsu Province, China
3 Huaian Center for Disease Control and Prevention, Huai-An City, Jiangsu Province, China
4 Jintan Center for Disease Control and Prevention, Jin-Tan City, Jiangsu Province, China
5 Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA
Zhengdong Zhang, E-mail: zdzhang{at}njmu.edu.cn
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