Wang J, et al. - Study's objective was to assess the association between alcohol consumption and breast tumor gene expression. Adding potential new insight into alcohol-related breast carcinogenesis, moderate alcohol consumption (i.e. 10+ grams/day, equivalent to one or more drinks/day) was associated with several specific and reproducible biological processes and pathways.

Methods

• The messenger RNA (mRNA) microarray data were examined from both invasive breast tumors (N=602) and tumor-adjacent normal tissues (N=508) from participants diagnosed with breast cancer in the Nurses’ Health Study (NHS) and NHSII.
• The clinicians used multivariable linear regression, controlling for other known breast cancer risk factors, to identify differentially expressed genes by pre-diagnostic alcohol intake.
• They conducted gene set enrichment analysis (GSEA) for pathway analysis.
• In RNA sequencing data of invasive breast tumors (N=166) from The Cancer Genome Atlas, differentially expressed genes or enriched pathway-defined gene sets with false discovery rate (FDR) <0.1 identified in tumors were validated.

Results

• Alcohol consumption in the NHS/NHSII did not significantly differentially express any individual genes.
• However, GSEA identified 33 and 68 pathway-defined gene sets at FDR <0.1 among 471 ER+ and 127 ER- tumors, respectively.
• In addition, these all were validated.
• Among ER+ tumors, an association was found between consuming 10+ grams of alcohol per day (vs. 0) and upregulation in RNA metabolism and transport, cell cycle regulation, and DNA repair, and downregulation in lipid metabolism.
• In addition to upregulation in RNA processing and cell cycle, alcohol intake was linked to overexpression of genes involved in cytokine signaling, including interferon and transforming growth factor (TGF)-β signaling pathways, and translation and post-translational modifications, among ER- tumors.
• They noticed lower lipid metabolism in both ER+ tumors and ER+ tumor-adjacent normal samples.
• Among ER- tumor-adjacent normal tissues, most of the significantly enriched gene sets identified in ER- tumors showed a similar enrichment pattern.