Alcohol consumption and breast tumor gene expression.

Area of Science:

• Oncology
• Molecular Biology
• Epidemiology

Background:

• Alcohol consumption is a known risk factor for breast cancer, particularly for estrogen receptor (ER)-positive tumors.
• The precise biological mechanisms linking alcohol intake to breast cancer remain incompletely understood.

Purpose of the Study:

• To investigate the molecular pathways affected by alcohol consumption in breast tumors.
• To identify specific gene expression changes associated with alcohol intake in ER-positive and ER-negative breast cancers.

Main Methods:

• Analysis of mRNA microarray data from 602 invasive breast tumors and 508 adjacent normal tissues from the Nurses' Health Study (NHS) and NHSII.
• Gene Set Enrichment Analysis (GSEA) to identify differentially expressed gene sets based on pre-diagnostic alcohol intake.
• Validation of findings using RNA sequencing data from The Cancer Genome Atlas (TCGA).

Main Results:

• No individual genes showed significant differential expression, but GSEA identified 33 (ER+) and 68 (ER-) pathway-defined gene sets associated with alcohol intake.
• In ER+ tumors, alcohol intake was linked to altered RNA metabolism, cell cycle regulation, DNA repair, and lipid metabolism.
• In ER- tumors, alcohol intake affected RNA processing, cell cycle, cytokine signaling (including interferon and TGF-β), and translation; lipid metabolism was also reduced.

Conclusions:

• Moderate alcohol consumption (≥10 grams/day) is associated with specific, reproducible biological pathway alterations in breast cancer.
• These findings provide novel insights into the molecular mechanisms of alcohol-related breast carcinogenesis.