导读：英国一项新研究发现，一个基因的状况与乳腺癌风险有关，通过血液检测可以在乳腺癌发病前数年就探知这个基因的异常变化，将来有望在此基础上开发出预测乳腺癌风险的方法。
检测基因变化或可预测乳腺癌
英国一项新研究发现，一个基因的状况与乳腺癌风险有关，通过血液检测可以在乳腺癌发病前数年就探知这个基因的异常变化，将来有望在此基础上开发出预测乳腺癌风险的方法。
医学研究认为，人体内不同的基因“版本”会导致不同的疾病风险，而基因的状况和功能也会因为某些原因发生变化，从而带来不同的疾病风险。因此，通过检查特定基因的状况来推断相应疾病风险，是医学研究热点之一。
英国帝国理工学院等机构研究人员在新一期《癌症研究》杂志上发表报告说，他们调查了1300多名女性的健康记录，她们在过去一二十年中都定期抽检血样，其中有600多人后来患上乳腺癌。
分析显示，在这些乳腺癌患者中，许多人在发病前数年就有一个名为ATM的基因出现了被称作甲基化的异常状况。对血液样本中的白细胞进行检测，可以获知该基因甲基化的程度。那些ATM基因甲基化程度最高的女性，后来患乳腺癌的风险比最低的女性要高89％。有的女性甚至在发病前11年就出现了ATM基因甲基化的情况。
Intragenic ATM Methylation in Peripheral Blood DNA as a Biomarker of Breast Cancer Risk
Kevin Brennan1, Montserrat Garcia-Closas4,6, Nick Orr4, Olivia Fletcher4, Robert Brown1,5, and James M. Flanagan
Few studies have evaluated the association between DNA methylation in white blood cells (WBC) and the risk of breast cancer. The evaluation of WBC DNA methylation as a biomarker of cancer risk is of particular importance as peripheral blood is often available in prospective cohorts and easier to obtain than tumor or normal tissues. Here, we used prediagnostic blood samples from three studies to analyze WBC DNA methylation of two ATM intragenic loci (ATMmvp2a and ATMmvp2b) and genome-wide DNA methylation in long interspersed nuclear element-1 (LINE1) repetitive elements. Samples were from a case–control study derived from a cohort of high-risk breast cancer families (KConFab) and nested case–control studies in two prospective cohorts: Breakthrough Generations Study (BGS) and European Prospective Investigation into Cancer and Nutrition (EPIC). Bisulfite pyrosequencing was used to quantify methylation from 640 incident cases of invasive breast cancer and 741 controls. Quintile analyses for ATMmvp2a showed an increased risk of breast cancer limited to women in the highest quintile [OR, 1.89; 95% confidence interval (CI), 1.36–2.64; P = 1.64 × 10−4]. We found no significant differences in estimates across studies or in analyses stratified by family history or menopausal status. However, a more consistent association was observed in younger than in older women and individually significant in KConFab and BGS, but not EPIC. We observed no differences in LINE1 or ATMmvp2b methylation between cases and controls. Together, our findings indicate that WBC DNA methylation levels at ATM could be a marker of breast cancer risk and further support the pursuit of epigenome-wide association studies of peripheral blood DNA methylation.
