Suppr超能文献

乳腺癌风险与同源重组 DNA 修复途径基因 XRCC2、XRCC3、NBS1 和 RAD51 中的常见单核苷酸多态性。

Breast cancer risk and common single nucleotide polymorphisms in homologous recombination DNA repair pathway genes XRCC2, XRCC3, NBS1 and RAD51.

机构信息

Department of Genetics, Faculty of Medical Sciences, New University of Lisbon, UNL, Rua da Junqueira 96, P-1349-008 Lisboa, Portugal.

出版信息

Cancer Epidemiol. 2010 Feb;34(1):85-92. doi: 10.1016/j.canep.2009.11.002. Epub 2009 Dec 9.

Abstract

The possible role for DNA repair deficiencies in cancer development, namely in breast cancer has been the subject of increasing interest since it has been reported that breast cancer patients might be deficient in the repair of DNA damage. Exposure to ionizing radiation has been pointed out as a risk factor for breast cancer, and the type of DNA lesions induced by this carcinogen can be repaired by homologous recombination DNA repair (HRR) pathway. To evaluate the potential modifying role of some single nucleotide polymorphisms (SNP) in HRR involved genes on the individual susceptibility to breast cancer we carried out a hospital based case-control study in a Caucasian Portuguese population (289 histological confirmed breast cancer patients and 548 control individuals). We genotyped 4 SNPs in 4 different HRR pathway genes, XRCC2 (Ex3+442G>A, R188H, rs3218536), XRCC3 (Ex8-5C>T, T241M, rs861539), NBS1 (Ex5-32C>G, E185Q, rs1805794) and RAD51 5'UTR (Ex1-59G>T, rs1801321), tagging 41 SNPs in these genes. The frequency of the different polymorphisms in the Portuguese control population is similar to the ones reported for other Caucasian populations, and the deviation of the Hardy-Weinberg equilibrium was only observed for the XRCC2 (Ex3+442G>A, R188H, rs3218536) polymorphism in the control population. The results obtained, after logistic regression analysis, did not reveal a major role of these polymorphisms on breast cancer susceptibility. However, when the population was stratified according to breast feeding (women that breast fed and women that never breast fed) it is observed, in women that never breast fed, that the heterozygous individuals for the XRCC2 (Ex3+442G>A, R188H, rs3218536) polymorphism have a decreased risk for breast cancer [adjusted OR=0.45; 95% CI=0.22-0.92] (P=0.03). Additionally, after stratification according to menopausal status, our results suggest that post-menopausal women carrying at least one variant allele for the XRCC3 (Ex8-5C>T, T241M, rs861539) polymorphism have a lower risk for breast cancer [adjusted OR=0.67; 95% CI, 0.47-0.94] (P=0.03). Most of the studies suggest that breastfeeding may be responsible for 2/3 of the estimate reduction of breast cancer. The longer the duration of breastfeeding the lower the potential risk associated with breast cancer. Therefore, in our study the potential protective role of the variant allele of XRCC2 (Ex3+442G>A, R188H, rs3218536), in never breast fed women, might be related with a more efficient DNA repair activity.

摘要

DNA 修复缺陷在癌症发展中的可能作用,特别是在乳腺癌中的作用,自报道乳腺癌患者可能在 DNA 损伤修复方面存在缺陷以来,一直是人们越来越感兴趣的话题。电离辐射的暴露已被指出是乳腺癌的一个风险因素,而这种致癌物诱导的 DNA 损伤类型可以通过同源重组 DNA 修复(HRR)途径修复。为了评估 HRR 相关基因中的一些单核苷酸多态性(SNP)在个体对乳腺癌易感性中的潜在修饰作用,我们在一个葡萄牙白种人人群中进行了一项基于医院的病例对照研究(289 例组织学证实的乳腺癌患者和 548 名对照个体)。我们对 4 个 HRR 途径基因中的 4 个 SNP(XRCC2(Ex3+442G>A,R188H,rs3218536)、XRCC3(Ex8-5C>T,T241M,rs861539)、NBS1(Ex5-32C>G,E185Q,rs1805794)和 RAD51 5'UTR(Ex1-59G>T,rs1801321))进行了基因分型,这些基因中的 41 个 SNP 标记。葡萄牙对照组人群中不同多态性的频率与其他白种人群报道的频率相似,仅在对照组人群中观察到 XRCC2(Ex3+442G>A,R188H,rs3218536)多态性偏离 Hardy-Weinberg 平衡。经过逻辑回归分析后,未发现这些多态性对乳腺癌易感性有主要作用。然而,当根据母乳喂养(母乳喂养的女性和从未母乳喂养的女性)对人群进行分层时,我们观察到从未母乳喂养的女性中,XRCC2(Ex3+442G>A,R188H,rs3218536)多态性杂合子的乳腺癌风险降低[调整后的 OR=0.45;95%CI=0.22-0.92](P=0.03)。此外,根据绝经状态进行分层后,我们的结果表明,至少携带一个 XRCC3(Ex8-5C>T,T241M,rs861539)多态性变异等位基因的绝经后女性患乳腺癌的风险较低[调整后的 OR=0.67;95%CI,0.47-0.94](P=0.03)。大多数研究表明,母乳喂养可能负责估计乳腺癌减少的 2/3。母乳喂养时间越长,与乳腺癌相关的潜在风险越低。因此,在我们的研究中,从未母乳喂养的女性中 XRCC2(Ex3+442G>A,R188H,rs3218536)的变异等位基因的潜在保护作用可能与更有效的 DNA 修复活性有关。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验