Intragenic ATM methylation in peripheral blood DNA as a biomarker of breast cancer risk
Menée à partir d'échantillons sanguins prélevés sur 640 patientes atteintes d'un cancer invasif du sein et sur 741 témoins, cette étude évalue l'association entre le niveau de méthylation dans les globules blancs de deux loci du gène ATM et le risque de développer la maladie
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 pre-diagnostic blood samples from three studies to analyze WBC DNA methylation of two ATM intragenic loci (ATMmvp2a and ATMmvp2b) and genome-wide DNA methylation in 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). Bisulphite 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 (1.36-2.64), p= 1.64x10-4). 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 compared to 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.
Cancer Research , résumé, 2012