hOGG1 Ser326Cys polymorphism and susceptibility to gallbladder cancer in a Chinese population

Authors

  • Xingyuan Jiao,

    Corresponding author
    1. Department of Hepatobiliary Surgery, Second Affiliated Hospital, Guangzhou Medical College, Guangzhou, Guangdong Province, The People's Republic of China
    2. Department of General Surgery and Transplantation Surgery, University Hospital Duisburg-Essen, Essen, Germany
    3. Department of Hepatobiliary Surgery, First Affiliated Hospital, Zhongshan University, Guangzhou, Guangdong Province, The People's Republic of China
    • Department of Hepatobiliary Surgery, Second Affiliated Hospital, Guangzhou Medical College, Guangzhou, Guangdong Province, The People's Republic of China
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    • Fax:+86-20-3415-2456.

  • Jiefu Huang,

    1. Department of Hepatobiliary Surgery, First Affiliated Hospital, Zhongshan University, Guangzhou, Guangdong Province, The People's Republic of China
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  • Shengli Wu,

    1. Department of General Surgery and Transplantation Surgery, University Hospital Duisburg-Essen, Essen, Germany
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  • MingdeLv,

    1. Department of Hepatobiliary Surgery, First Affiliated Hospital, Zhongshan University, Guangzhou, Guangdong Province, The People's Republic of China
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  • Yize Hu,

    1. Department of Hepatobiliary Surgery, Second Affiliated Hospital, Guangzhou Medical College, Guangzhou, Guangdong Province, The People's Republic of China
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  • Jianfu,

    1. Department of General Surgery and Transplantation Surgery, University Hospital Duisburg-Essen, Essen, Germany
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  • Xiaokang Su,

    1. Department of Hepatology, Cancer Center Research Institute, Zhongshan University, Guangzhou, Guangdong Province, The People's Republic of China
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  • Canqiao Luo,

    1. Deparment of Pathology, Zhongshan Unversity School of Medicine, Zhongshan University, Guangzhou, Guangdong Province, The People's Republic of China
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  • CE Broelsch

    1. Department of General Surgery and Transplantation Surgery, University Hospital Duisburg-Essen, Essen, Germany
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Abstract

The human oxoguanine glycosylase 1(hOGG1) gene encodes a DNA glycosylase that is involved in excision repair of 8-OH-dG (8-hydroxy-2-deoxyguanine) from oxidatively-damaged DNA. To determine whether hOGG1 plays a role in the risk for adenocarcinoma of the gallbladder, we tested the association of this polymorphism with gallbladder cancer in a Chinese population-based, case control study of 204 cases and 209 controls. The subjects were genotyped with a polymerase chain reaction-restriction fragment length polymorphism (PCR–RELP) assay. The association between the genetic polymorphism of this gene and risk of the cancer was examined by using a multivariate analysis. We found that the distribution of hOGG1 Ser326Cys genotypes among controls (Ser/Ser, 37.3%; Ser/Cys, 53.6% and Cys/Cys, 9.1%) was significantly different from that among gallbladder cancer cases (Ser/Ser, 43.1%; Ser/Cys, 36.3% and Cys/Cys, 20.6%). Significantly increased risk for gallbladder cancer was both the hOGG1 326Ser/Cys (Odds ratio [OR] = 1.9, 95% confidence interval (CI) = 1.0–3.7) and hOGG1 326Cys/Cys genotypes (OR = 4.5, 95% CI = 1.1–22.4). We observed no statistically significant association between hOGG1 genotype and gallbladder cancer association in gallstone absence. In contrast, a near-significant increase in risk for gallbladder cancer was observed for gallstone presence with the hOGG1 326Ser/Cys genotype (OR = 2.2, CI = 1.4–3.5) whereas a significant increase in association for gallbladder cancer was observed for gallstone presence with the 326Cys/Cys genotype (OR = 6.1, CI = 2.1–27.2). These data corresponded with the fact that a significant trend towards increased association for gallbladder cancer was observed with potentially higher-risk hOGG1 genotypes in gallstone presence(p < 0.001, χ2 trend test)but not in gallstone absence(p = 0.89, χ2 trend test). A significant increase in risk for gallbladder cancer was observed for larger gallstone (those with stone diameters 2 cm or greater) with the hOGG1 326Ser/Cys(OR = 1.9, 95% CI = 1.1–2.9) and hOGG1 326Cys/Cys genotypes(OR = 5.9, 95% CI = 1.6–18.0). These data are consistent with the observation that a significant trend towards increased risk for gallbladder cancer was observed with potentially higher-risk hOGG1 genotypes in gallbladder cancer patients with larger gallstone (p < 0.001, χ2 trend test). However, we observed no statistically significant association between hOGG1 genotype and gallbladder cancer risk in gallbladder cancer patients with smaller gallstone (those with stone diameters 2 cm smaller) (hOGG1 326Ser/Cys:OR = 2.2, 95% CI = 0.8–4.0; hOGG1 326Cys/Cys:OR = 2.9, 95% CI = 0.6–29.4; p = 0.06, χ2 tread test). These results suggest that hOGG1 Ser326Cys polymorphism is associated with gallbladder cancer risk. © 2007 Wiley-Liss, Inc.

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