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DNA修复基因中的单核苷酸多态性与宫颈癌风险:一项病例对照研究。

Single nucleotide polymorphisms in DNA repair genes and risk of cervical cancer: A case-control study.

作者信息

Zhang Lihua, Ruan Zhenchao, Hong Qingya, Gong Xiangzhen, Hu Zhengguang, Huang Yan, Xu Aidi

机构信息

Department of Radiation Oncology, Cancer Hospital, Fudan University, Shanghai 200032.

出版信息

Oncol Lett. 2012 Feb;3(2):351-362. doi: 10.3892/ol.2011.463. Epub 2011 Oct 26.

Abstract

In this report, we describe a case control study in a Chinese population aimed at identifying possible associations between susceptibility to cervical cancer and single nucleotide polymorphisms in XRCC1 194C>T, XRCC1 280G>A, XRCC1 399G>A, ERCC2 751A>C, ERCC2 156C>A, ERCC1 118C>T, PARP1 762T>C, RAD51 135G>C and HER2 655A>G. The cases comprised 154 patients: 80 cervical squamous cell carcinomas (SCCs), 2 adenocarcinomas and 72 cervical intraepithelial neoplasias (CINs). A total of 177 healthy women were recruited as the controls. A significant association was found between ERCC1 118C>T and SCC in the additive genetic model [odds ratio (OR)=1.711; 95% confidence interval (CI), 1.089-2.880; p=0.021] and the dominant genetic model (OR=1.947; 95% CI, 1.056-3.590; p=0.033). Among women with a smoking family member, ERCC1 118C>T increased SCC risk in the additive model (OR=2.800; 95% CI, 1.314-5.968; p=0.008). For women who had first intercourse before 22 years of age, XRCC1 280G>A was found to act as a protective factor for SCC under the additive model (OR=0.228; 95% CI, 0.058-0.900; p=0.035), while RAD51 135G>C was a risk factor for CIN (OR=4.246; 95% CI, 1.335-13.502; p=0.014). For women who had first intercourse after 22 years of age, the additive genetic model showed RAD51 135G>C (OR=0.359; 95% CI, 0.138-0.934; p=0.036) and HER2 655A>G (OR=0.309; 95% CI, 0.098-0.972; p=0.045) to be protective factors for SCC. XRCC1 399G>A increased CIN risk among women who first gave birth before the age of 22 in the additive genetic model (OR=4.459; 95% CI, 1.139-17.453; p=0.032). For those who first gave birth after age 22, ERCC1 118C>T was found to be a risk factor for SCC in the additive genetic model (OR=1.884; 95% CI, 1.088-3.264; p=0.024). A significant interaction was observed between RAD51 135G>C and age at first intercourse (p(interaction)=0.033 for SCC, p(interaction)=0.021 for CIN), as well with sexual partner number (p(interaction)=0.001 for SCC). The interaction between HER2 655A>G and age at first intercourse, ERCC2 156C>A and family smoking status and XRCC1 280G>A and alcohol consumption were significant, with p(interaction)=0.023 for SCC, p(interaction)=0.021 for CIN and p(interaction)=0.025 for SCC, respectively.

摘要

在本报告中,我们描述了一项针对中国人群的病例对照研究,旨在确定宫颈癌易感性与XRCC1 194C>T、XRCC1 280G>A、XRCC1 399G>A、ERCC2 751A>C、ERCC2 156C>A、ERCC1 118C>T、PARP1 762T>C、RAD51 135G>C和HER2 655A>G单核苷酸多态性之间的可能关联。病例包括154例患者:80例宫颈鳞状细胞癌(SCC)、2例腺癌和72例宫颈上皮内瘤变(CIN)。共招募了177名健康女性作为对照。在相加遗传模型中,发现ERCC1 118C>T与SCC之间存在显著关联[比值比(OR)=1.711;95%置信区间(CI),1.089 - 2.880;p=0.021],在显性遗传模型中(OR=1.947;95% CI,1.056 - 3.590;p=0.033)。在有吸烟家庭成员的女性中,ERCC1 118C>T在相加模型中增加了SCC风险(OR=2.800;95% CI,1.314 - 5.968;p=0.008)。对于首次性交在22岁之前的女性,在相加模型中发现XRCC1 280G>A对SCC起保护作用(OR=0.228;95% CI,0.058 - 0.900;p=0.035),而RAD51 135G>C是CIN的危险因素(OR=4.246;95% CI,1.335 - 13.502;p=0.014)。对于首次性交在22岁之后的女性,相加遗传模型显示RAD51 135G>C(OR=0.359;95% CI,0.138 - 0.934;p=0.036)和HER2 655A>G(OR=0.309;95% CI,0.098 - 0.972;p=0.045)是SCC的保护因素。在相加遗传模型中,XRCC1 399G>A增加了首次生育在22岁之前女性的CIN风险(OR=4.459;95% CI,1.139 - 17.453;p=0.032)。对于首次生育在22岁之后的女性,在相加遗传模型中发现ERCC1 118C>T是SCC的危险因素(OR=1.884;95% CI,1.088 - 3.264;p=0.024)。观察到RAD51 135G>C与首次性交年龄之间存在显著交互作用(SCC的p(交互作用)=0.033,CIN的p(交互作用)=

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