Global DNA methylation and one-carbon metabolism gene polymorphisms and the risk of breast cancer in the Sister Study.

Abstract

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 35-74 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 with those in the highest quartile (hazard ratio = 1.75; 95% confidence interval 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 three single-nucleotide polymorphisms 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.

• Authors: Lisa A Deroo, Sophia C E Bolick, Zongli Xu, David M Umbach, David Shore, Clarice R Weinberg, Dale P Sandler, Jack A Taylor
• Journal: Carcinogenesis (Carcinogenesis) Vol. 35 Issue 2 Pg. 333-8 (Feb 2014) ISSN: 1460-2180 [Electronic] England
• PMID: 24130171 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Biomarkers, Tumor
• Carbon

Topics

• Adult
• Aged
• Biomarkers, Tumor (genetics)
• Breast Neoplasms (blood, genetics, pathology)
• Carbon (metabolism)
• Case-Control Studies
• DNA Methylation
• Female
• Follow-Up Studies
• Genome, Human
• Humans
• Long Interspersed Nucleotide Elements (genetics)
• Middle Aged
• Neoplasm Staging
• Polymorphism, Single Nucleotide (genetics)
• Prognosis
• Prospective Studies
• Risk Factors