DNA methylation and breast cancer-associated variants

Area of Science:

• Genomics
• Epigenetics
• Cancer Research

Background:

• A breast cancer polygenic risk score (PRS) using 313 common variants accurately predicts disease risk.
• Investigating genetic variation, regulation, and expression clarifies molecular alterations in breast cancer risk variants.

Purpose of the Study:

• To examine relationships between genetic variation, DNA methylation, and gene expression in breast cancer.
• To identify molecular mechanisms underlying breast cancer risk variants.

Main Methods:

• Genome-wide DNA methylation was quantified using MethylationEPIC in 1152 Asian breast cancer patients.
• DNA methylation quantitative trait loci (mQTL) mapping was performed for 235 PRS variants.
• mQTL stability across lifetime and overlap with expression quantitative trait loci (eQTLs) were analyzed.

Main Results:

• Breast cancer PRS was not directly associated with DNA methylation levels.
• Significant cis-mQTLs were identified, with many variants showing stability across different life stages.
• Ninety-three DNA methylation-associated variants were also cis-eQTLs, suggesting a link between methylation and gene expression.

Conclusions:

• Multiple loci within the breast cancer PRS are associated with DNA methylation, contributing to the polygenic nature of the disease.
• Identified mQTLs are generally stable over time.
• Integrating DNA methylation and expression data may reveal novel candidate genes for breast cancer.