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Alcohol consumption and breast tumor gene expression


Alcohol consumption is an established risk factor for breast cancer and the association generally appears stronger among estrogen receptor (ER)-positive tumors. However, the biological mechanisms underlying this association are not completely understood.
We analyzed messenger RNA (mRNA) microarray data 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. Multivariable linear regression, controlling for other known breast cancer risk factors, was used to identify differentially expressed genes by pre-diagnostic alcohol intake. For pathway analysis, we performed gene set enrichment analysis (GSEA). Differentially expressed genes or enriched pathway-defined gene sets with false discovery rate (FDR) <0.1 identified in tumors were validated in RNA sequencing data of invasive breast tumors (N = 166) from The Cancer Genome Atlas.
No individual genes were significantly differentially expressed by alcohol consumption in the NHS/NHSII. However, GSEA identified 33 and 68 pathway-defined gene sets at FDR <0.1 among 471 ER+ and 127 ER- tumors, respectively, all of which were validated. Among ER+ tumors, consuming 10+ grams of alcohol per day (vs. 0) was associated with upregulation in RNA metabolism and transport, cell cycle regulation, and DNA repair, and downregulation in lipid metabolism. Among ER- tumors, 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. Lower lipid metabolism was observed in both ER+ tumors and ER+ tumor-adjacent normal samples. Most of the significantly enriched gene sets identified in ER- tumors showed a similar enrichment pattern among ER- tumor-adjacent normal tissues.
Our data suggest that ADHD moderate alcohol consumption (i.e. 10+ grams/day, equivalent to one or more drinks/day) is associated with several specific and reproducible biological processes and pathways, which adds potential new insight into alcohol-related breast carcinogenesis.



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October is the ADHD Awareness Month and our 2017 theme is “Knowing is Better: ADHD Across the Life Span.” It’s better for parents to know that ADHD might be part of the picture so they can seek out the help their children need; it’s better for young adults to know about their ADHD so they might arrange for appropriate accommodations in school or the workplace; and it’s better for adults to recognize their ADHD instead of feeling destined to a life of underachievement and frustration.
We are pleased to bring back the ADHD Awareness Month Video Contest this year. You can help us raise awareness of ADHD by creating and submitting a short video to share your experience with ADHD or your best tip for living well with ADHD or supporting someone who has ADHD. Videos can be submitted in one of four categories: Parent, Child, Adult or Professional. There will be valuable prizes for the top videos submitted by children, parents and adults. We have a lot we can learn from each other and a lot the world can learn from us.
Before you go, take a few minutes to check out our site. Just click on any of the logos at the bottom of this page and you’ll have access to some of the best information and help for ADHD that you’ll find on the web.