Global DNA methylation and one-carbon metabolism gene polymorphisms and the risk of breast cancer in the Sister Study
Menée à partir d'échantillons de sang périphérique prélevés sur 294 patientes atteintes d'un cancer du sein et 646 témoins inclus dans la cohorte "Sister Study", cette étude évalue l'association entre un faible niveau de méthylation de l'ADN et le risque de cancer du sein
Global decrease in DNA methylation is a common feature of cancer and is associated with genomic and chromosomal instability. Retrospective case-control studies have reported that cancer patients have lower global methylation levels in blood DNA than do controls. We used prospectively collected samples and a case-cohort study design to examine global DNA methylation and incident breast cancer in 294 cases and a sample of 646 non-cases in the Sister Study, a study of 50,884 women aged 35 to 74 years who had not been diagnosed with breast cancer at the time of blood draw. Global methylation in DNA from peripheral blood was assessed by pyrosequencing of the LINE-1 repetitive element. Quartiles of LINE-1 methylation levels were associated with the risk of breast cancer in a dose-dependent fashion (P, trend=0.002), with an increased risk observed among women in the lowest quartile compared to those in the highest quartile (HR =1.75; 95% CI 1.19, 2.59). We also examined 22 polymorphisms in 10 one-carbon metabolism genes in relation to both LINE-1 methylation levels and breast cancer. We found 3 SNPs in those genes associated with LINE-1 methylation: SLC19A1 (rs1051266); MTRR (rs10380); and MTHFR (rs1537514), one of which was also associated with breast cancer risk: MTHFR (rs1537514). PON1 (rs757158) was associated with breast cancer but not methylation. Our finding that LINE-1 under-methylation was present in blood collected from women before clinical detection of their tumor provides evidence from a prospective study that lower global methylation is associated with increased risk of breast cancer.
http://carcin.oxfordjournals.org/content/early/2013/10/11/carcin.bgt342.abstract