Jiao Xingyuan, Huang Jiefu, Wu Shengli, Lv Mingde, Hu Yize, Su Xiaokang, Luo Canqiao, Ce Broelsch
Department of Hepatobiliary Surgery, Second Affiliated Hospital, Guangzhou Medical College, Guangzhou, Guangdong Province, The People's Republic of China.
Int J Cancer. 2007 Aug 1;121(3):501-5. doi: 10.1002/ijc.22748.
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, 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 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, chi(2) 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, chi(2) tread test). These results suggest that hOGG1 Ser326Cys polymorphism is associated with gallbladder cancer risk.
人8-氧鸟嘌呤糖基化酶1（hOGG1）基因编码一种DNA糖基化酶，该酶参与从氧化损伤的DNA中切除8-羟基-2'-脱氧鸟苷（8-OH-dG）。为了确定hOGG1是否在胆囊腺癌风险中起作用，我们在一项基于中国人群的病例对照研究中，对204例病例和209例对照进行了该多态性与胆囊癌关联的检测。通过聚合酶链反应-限制性片段长度多态性（PCR-RELP）分析对受试者进行基因分型。使用多变量分析检查该基因的遗传多态性与癌症风险之间的关联。我们发现，对照组中hOGG1 Ser326Cys基因型的分布（Ser/Ser，37.3%；Ser/Cys，53.6%；Cys/Cys，9.1%）与胆囊癌病例组中的分布（Ser/Ser，43.1%；Ser/Cys，36.3%；Cys/Cys，20.6%）有显著差异。hOGG1 326Ser/Cys（优势比[OR]=1.9，95%置信区间[CI]=1.0-3.7）和hOGG1 326Cys/Cys基因型（OR=4.5，95%CI=1.1-22.4）患胆囊癌的风险均显著增加。在无胆结石的情况下，我们未观察到hOGG1基因型与胆囊癌关联之间存在统计学显著关联。相反，在有胆结石且hOGG1 326Ser/Cys基因型的情况下，观察到胆囊癌风险近乎显著增加（OR=2.2，CI=1.4-3.5），而在有胆结石且326Cys/Cys基因型的情况下，观察到胆囊癌关联显著增加（OR=6.1，CI=2.1-27.2）。这些数据与以下事实相符：在有胆结石的情况下，观察到胆囊癌关联增加的显著趋势与潜在高风险的hOGG1基因型有关（p<0.001，卡方趋势检验），而在无胆结石的情况下则无此趋势（p=0.89，卡方趋势检验）。在有较大胆结石（直径2cm或更大）且hOGG1 326Ser/Cys（OR=1.9，95%CI=1.1-2.9）和hOGG1 326Cys/Cys基因型（OR=5.9，95%CI=1.6-18.0）的情况下，观察到胆囊癌风险显著增加。这些数据与以下观察结果一致：在有较大胆结石的胆囊癌患者中，观察到胆囊癌风险增加的显著趋势与潜在高风险的hOGG1基因型有关（p<0.001，卡方趋势检验）。然而，在有较小胆结石（直径小于2cm）的胆囊癌患者中，我们未观察到hOGG1基因型与胆囊癌风险之间存在统计学显著关联（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，卡方趋势检验）。这些结果表明，hOGG1 Ser326Cys多态性与胆囊癌风险相关。
