碱基切除修复基因多态性与绝经后日本女性子宫内膜癌风险相关。

Polymorphisms in base excision repair genes are associated with endometrial cancer risk among postmenopausal Japanese women.

机构信息

*Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute; †Department of Epidemiology, Nagoya University Graduate School of Medicine; ‡Department of Planning and Information, Aichi Prefectural Institute of Public Health; §Department of Gynecologic Oncology, Aichi Cancer Center Hospital; ∥Department of Public Health and Occupational Medicine, Mie University Graduate School of Medicine; and ¶Department of Preventive Medicine, Kyushu University Faculty of Medical Sciences.

出版信息

Int J Gynecol Cancer. 2013 Nov;23(9):1561-8. doi: 10.1097/IGC.0b013e3182a80a7e.

DOI:10.1097/IGC.0b013e3182a80a7e

PMID:24172093

Abstract

OBJECTIVES

Polymorphisms in base excision repair (BER) genes are associated with risk for several types of cancers but have not been studied with respect to endometrial cancer among Japanese women. Therefore, we conducted a case-control study to explore the association between polymorphisms in BER genes and the risk for endometrial cancer.

METHODS/MATERIALS: This study included a total of 91 postmenopausal subjects with endometrial cancer and 261 controls without cancer who visited the Aichi Cancer Center between 2001 and 2005. We focused on single nucleotide polymorphisms within coding regions of 5 BER genes (OGG1, MUTYH, XRCC1, APEX1, and PARP1). To assess lifestyle in the etiology of endometrial cancer, we used a self-administered questionnaire. Associations were evaluated using multivariate unconditional logistic regression models. We also assessed whether there were intergenic associations or an interaction with obesity.

RESULTS

We observed a significant association between endometrial cancer risk and XRCC1 rs1799782 (C > T, Arg194Trp) and XRCC1 rs25487 (G > A, Arg399Gln). We uncovered a significant association between obesity (body mass index, ≥ 25) and rs25487. The XRCC1 polymorphisms were in complete linkage disequilibrium, and the XRCC1 haplotype TG associated significantly with endometrial cancer risk. The interaction between the CA haplotype and body mass index was marginally significant, whereas interaction between haplotype in XRCC1 and rs1136410 (PARP1) was not significant.

CONCLUSIONS

We found a significant association between endometrial cancer risk and XRCC1 polymorphisms and haplotype TG in postmenopausal Japanese women.

摘要

目的

碱基切除修复（BER）基因中的多态性与几种类型的癌症风险相关，但尚未针对日本女性的子宫内膜癌进行研究。因此，我们进行了一项病例对照研究，以探讨 BER 基因多态性与子宫内膜癌风险之间的关系。

方法/材料：本研究共纳入 91 名绝经后患有子宫内膜癌的患者和 261 名无癌症的对照组，他们于 2001 年至 2005 年期间在爱知县癌症中心就诊。我们专注于 5 个 BER 基因（OGG1、MUTYH、XRCC1、APEX1 和 PARP1）编码区的单核苷酸多态性。为了评估生活方式在子宫内膜癌病因中的作用，我们使用了一份自我管理的问卷。使用多变量非条件逻辑回归模型评估关联。我们还评估了是否存在基因间关联或与肥胖的相互作用。

结果

我们观察到 XRCC1 rs1799782（C>T，Arg194Trp）和 XRCC1 rs25487（G>A，Arg399Gln）与子宫内膜癌风险之间存在显著关联。我们发现肥胖（体重指数≥25）与 rs25487 之间存在显著关联。XRCC1 多态性完全连锁不平衡，XRCC1 单倍型 TG 与子宫内膜癌风险显著相关。CA 单倍型和体重指数之间的相互作用具有边缘显著性，而 XRCC1 中的单倍型与 rs1136410（PARP1）之间的相互作用不显著。