hOGG1 Ser326Cys polymorphism and susceptibility to gallbladder cancer in a Chinese population
hOGG1 Ser326Cys polymorphism and susceptibility to gallbladder cancer in a Chinese population
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DOI：
10.1002/ijc.22748
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发表时间：
2007-08-01
影响因子：
6.4
通讯作者：
Su, Xiaokang
中科院分区：
文献类型：
--
作者：
Jiao, Xingyuan;Huang, Jiefu;Su, Xiaokang
人氧代鸟嘌呤糖基化酶1（hOGG 1）基因编码一种DNA糖基化酶，参与氧化损伤DNA中8-OH-dG（8-羟基-2-脱氧鸟嘌呤）的切除修复。为了确定hOGG 1是否在胆囊腺癌的风险中起作用，我们在一项基于中国人群的病例对照研究中检测了该多态性与胆囊癌的相关性，该研究包括204例病例和209例对照。受试者的基因分型与聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析。通过多变量分析，检测该基因的遗传多态性与癌症风险之间的关联。结果表明：hOGG 1 Ser 326 Cys基因型在胆囊癌患者中的分布（Ser/Ser，37.3%; Ser/Cys，53.6%; Cys/Cys，9.1%）与胆囊癌患者中的分布（Ser/ Ser，43.1%; Ser/Cys，36.3%; Cys/Cys，20.6%）有显著性差异。hOGG 1 326 Ser/Cys基因型（比值比[OR] = 1.9，95%置信区间（CI）1.0-3.7）和hOGG 1 326 Cys/Cys基因型（OR = 4.5，95% CI 1.1-22.4）均显著增加胆囊癌的风险。我们没有观察到hOGGI基因型与胆囊癌之间的统计学显著相关性。与此相反，hOGG 1 326 Ser/Cys基因型与胆囊结石的发生有显著相关性（OR = 2.2，CI = 1.4-3.5），而326 Cys/Cys基因型与胆囊结石的发生有显著相关性（OR = 6.19，CI = 2.1-27.2）。这些数据与以下事实相对应：在存在胆结石的情况下，观察到潜在高风险hOGGI基因型与胆囊癌的关联增加的显著趋势（p < 0.001，卡方（2）趋势检验），但在不存在胆结石的情况下则没有（p = 0.89，卡方（2）趋势检验）。hOGGI 326 Ser/Cys（OR = 1.9，95%CI = 1.1-2.9）和hOGG 1 326 Cys/ Cys基因型（OR = 5.9，95%CI = 1.6-18.0）的较大胆囊结石（结石直径≥ 2 cm）患者的胆囊癌风险显著增加。这些数据与以下观察结果一致，即在具有较大胆结石的胆囊癌患者中，观察到具有潜在较高风险的hOGGI基因型的胆囊癌风险增加的显著趋势（P < 0.001，卡方（2）趋势检验）。然而，我们没有观察到hOGGI基因型与胆囊癌患者的胆囊结石较小（结石直径小于2 cm）的胆囊癌风险之间存在统计学显著相关性（hOGG 1 326 Ser/Cys：OR = 2.2，95% CI 0.8-4.0）hOGG 1 326 Cys/Cys：OR = 2.9，95% CI = 0.6-29。4; P = 0.06，X胎面试验）。提示hOGGI基因Ser 326 Cys多态性与胆囊癌风险相关。(c)2007 Wiley-Liss，Inc.
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 signi cantly 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 hOGGI 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 = 6.19 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 hOGGI genotypes in gallstone presence(p < 0.001, chi(2) trend test)but not in gallstone absence(p = 0.89, chi(2) 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 hOGGI 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 hOGGI genotypes in gallbladder cancer patients with larger gallstone (P < 0.001, chi(2) trend test). However, we observed no statistically significant association between hOGGI 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, X tread test). These results suggest that hOGGI Ser326Cys polymorphism is associated with gallbladder cancer risk. (c) 2007 Wiley-Liss, Inc.