近日,，英國一項(xiàng)新研究發(fā)現(xiàn),，一個基因的狀況與乳腺癌風(fēng)險有關(guān),，通過血液檢測可以在乳腺癌發(fā)病前數(shù)年就探知這個基因的異常變化,，將來有望在此基礎(chǔ)上開發(fā)出預(yù)測乳腺癌風(fēng)險的方法。相關(guān)論文在新一期《癌癥研究》（Cancer Research）雜志上發(fā)表,。
醫(yī)學(xué)研究認(rèn)為,，人體內(nèi)不同的基因“版本”會導(dǎo)致不同的疾病風(fēng)險,，而基因的狀況和功能也會因?yàn)槟承┰虬l(fā)生變化，從而帶來不同的疾病風(fēng)險,。因此,，通過檢查特定基因的狀況來推斷相應(yīng)疾病風(fēng)險，是醫(yī)學(xué)研究熱點(diǎn)之一,。
英國帝國理工學(xué)院等機(jī)構(gòu)研究人員報告說,，他們調(diào)查了1300多名女性的健康記錄，她們在過去一二十年中都定期抽檢血樣,，其中有600多人后來患上乳腺癌,。
分析顯示，在這些乳腺癌患者中,，許多人在發(fā)病前數(shù)年就有一個名為ATM的基因出現(xiàn)了被稱作甲基化的異常狀況,。對血液樣本中的白細(xì)胞進(jìn)行檢測，可以獲知該基因甲基化的程度,。那些ATM基因甲基化程度最高的女性,，后來患乳腺癌的風(fēng)險比最低的女性要高89％。有的女性甚至在發(fā)病前11年就出現(xiàn)了ATM基因甲基化的情況,。（生物谷Bioon.com）
doi:10.1158/0008-5472.CAN-11-3157
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Intragenic ATM Methylation in Peripheral Blood DNA as a Biomarker of Breast Cancer Risk
Kevin Brennan1, Montserrat Garcia-Closas4,6, Nick Orr4, Olivia Fletcher4, Michael Jones6, Alan Ashworth4, Anthony Swerdlow6, Heather Thorne; on behalf of KConFab Investigators7, Elio Riboli3, Paolo Vineis2,8, Miren Dorronsoro9, Francoise Clavel-Chapelon10, Salvatore Panico11, N. Charlotte Onland-Moret12, Dimitrios Trichopoulos13,14, Rudolf Kaaks15, Kay-Tee Khaw16, Robert Brown1,5, and James M. Flanagan1
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.
