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Open Access Research article

The role of TNF genetic variants and the interaction with cigarette smoking for gastric cancer risk: a nested case-control study

Jae Jeong Yang1, Kwang-Pil Ko12, Lisa Y Cho1, Aesun Shin3, Jin Gwack1, Soung-Hoon Chang4, Hai-Rim Shin3, Keun-Young Yoo1, Daehee Kang156 and Sue K Park15*

Author Affiliations

1 Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea

2 Division of Epidemiology and Health Index, Center for Genome Science, Korea Center for Disease Control and Prevention, Seoul, Korea

3 National Cancer Control Research Institute, National Cancer Center, Goyang, Korea

4 Department of Preventive Medicine, Konkuk University, Chungju, Korea

5 Seoul National University Cancer Research Institute, Seoul, Korea

6 Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine, Seoul National University, Seoul, Korea

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BMC Cancer 2009, 9:238  doi:10.1186/1471-2407-9-238

Published: 17 July 2009

Abstract

Background

The aim of this study was to investigate the role of TNF genetic variants and the combined effect between TNF gene and cigarette smoking in the development of gastric cancer in the Korean population.

Methods

We selected 84 incident gastric cancer cases and 336 matched controls nested within the Korean Multi-Center Cancer Cohort. Six SNPs on the TNF gene, TNF-α-238 G/A, -308 G/A, -857 C/T, -863 C/A, -1031 T/C, and TNF-β 252 A/G were genotyped. The ORs (95% CIs) were calculated using unconditional logistic regression model to detect each SNP and haplotype-pair effects for gastric cancer. The combined effects between the TNF gene and smoking on gastric cancer risk were also evaluated. Multi dimensionality reduction (MDR) analyses were performed to explore the potential TNF gene-gene interactions.

Results

TNF-α-857 C/T containing the T allele was significantly associated with an increased risk of gastric cancer and a linear trend effect was observed in the additive model (OR = 1.6, 95% CI 1.0–2.5 for CT genotype; OR = 2.6, 95% CI 1.0–6.4 for TT genotype). All haplotype-pairs that contained TCT or CCC of TNF-α-1031 T/C, TNF-α-863 C/A, and TNF-α-857 C/T were associated with a significantly higher risk for gastric cancer only among smokers. In the MDR analysis, regardless of smoking status, TNF-α-857 C/T was included in the first list of SNPs with a significant main effect.

Conclusion

TNF-α-857 C/T polymorphism may play an independent role in gastric carcinogenesis and the risk for gastric cancer by TNF genetic effect is pronounced by cigarette smoking.