TGFBR1 tagging SNPs and gastric cancer susceptibility: A two-stage case–control study in chinese population

Authors

  • Jianjian Chen,

    1. Institute of Digestive Endoscopy and Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
    2. Department of Health Promotion, Wuxi Center for Disease Prevention and Control, Wuxi, China
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  • Lin Miao,

    1. Institute of Digestive Endoscopy and Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
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  • Guangfu Jin,

    Corresponding author
    1. Department of Epidemiology and Biostatistics, Ministry of Education (MOE) Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China
    2. Section of Clinical Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China
    • Institute of Digestive Endoscopy and Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China.

      Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, 140 Han-Zhong Road, Nanjing 210029, China.

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  • Chuanli Ren,

    1. Medical Lab, Northern Jiangsu People's Hospital, Yangzhou, China
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  • Qiao Ke,

    1. Department of Epidemiology and Biostatistics, Ministry of Education (MOE) Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China
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  • Yun Qian,

    1. Department of Health Promotion, Wuxi Center for Disease Prevention and Control, Wuxi, China
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  • Meihua Dong,

    1. Department of Health Promotion, Wuxi Center for Disease Prevention and Control, Wuxi, China
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  • Huizhang Li,

    1. Department of Epidemiology and Biostatistics, Ministry of Education (MOE) Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China
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  • Qin Zhang,

    1. Department of Epidemiology and Biostatistics, Ministry of Education (MOE) Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China
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  • Yanbing Ding,

    1. Department of Gastroenterology, Yangzhou First People's Hospital, Yangzhou, China
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  • Zhigang Yan,

    1. Department of Gastroenterology, Yangzhou First People's Hospital, Yangzhou, China
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  • Jianming Wang,

    1. Department of Epidemiology and Biostatistics, Ministry of Education (MOE) Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China
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  • Zheng Liu,

    1. Institute of Digestive Endoscopy and Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
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  • Zhibin Hu,

    1. Department of Epidemiology and Biostatistics, Ministry of Education (MOE) Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China
    2. Section of Clinical Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China
    3. State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China
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  • Yaochu Xu,

    1. Department of Epidemiology and Biostatistics, Ministry of Education (MOE) Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China
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  • Guozhong Ji,

    Corresponding author
    1. Institute of Digestive Endoscopy and Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
    • Institute of Digestive Endoscopy and Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing 210011, China.

      Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, 140 Han-Zhong Road, Nanjing 210029, China.

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  • Hongbing Shen

    1. Department of Epidemiology and Biostatistics, Ministry of Education (MOE) Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China
    2. Section of Clinical Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China
    3. State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China
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  • Jianjian Chen and Lin Miao contributed equally to this work.

Abstract

The transforming growth factor (TGF)-β is a potent growth inhibitor primarily responsible for cell growth, differentiation, and apoptosis, and frequently perturbed during development of tumors, including gastric cancer. TGF-β receptor type I (TGFβR1) may be a modifier of cancer risk by constitutively decreasing the TGF-β inhibitory signals during early tumorigenesis and increasing the TGF-β signals in tumor progression. In this study, we hypothesized that genetic variants of TGFBR1 may influence the risk of gastric cancer. We conducted a two-stage case–control study of gastric cancer, including 650 cases and 683 controls in the first stage and 484 cases and 348 controls in the second stage, and genotyped five tagging single nucleotide polymorphisms (SNPs) to represent common variants in the whole TGFBR1 gene. In the first stage, two SNPs rs6478974 and rs10512263 were found to be potentially associated with risk of gastric cancer (P = 3.35 × 10−3 for rs6478974 AT vs. TT and P = 0.033 for rs10512263 CT vs. TT), which were further confirmed in the second stage with similar effects (P = 0.144 and 0.049, respectively). After combining the two stages, we found that these two SNPs were associated with a significantly increased risk of gastric cancer in dominant models [adjusted odds ratio (OR) = 1.36, 95% confidence interval (CI): 1.14–1.63 for rs6478974 AT/AA vs. TT; adjusted OR = 1.26, 95% CI: 1.05–1.50 for rs10512263 CT/CC vs. TT] or additive model (adjusted OR = 1.23, 95% CI: 1.08–1.40 for rs6478974). These findings indicate that TGFBR1 polymorphisms may be implicated with the development of gastric cancer in Han-Chinese population. © 2012 Wiley Periodicals, Inc.

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