Abstract
Breast cancer is the leading cause of cancer-related disease in women. Cumulative evidence supports a causal role of alcohol intake and breast cancer incidence. In this study, we explore the change on expression of genes involved in the biological pathways through which alcohol has been hypothesized to impact breast cancer risk, to shed new insights on possible mechanisms affecting the survival of breast cancer patients. Here, we performed differential expression analysis at individual genes and gene set levels, respectively, across survival and breast cancer subtype data. Information about postdiagnosis breast cancer survival was obtained from 1977 Caucasian female participants in the Molecular Taxonomy of Breast Cancer International Consortium. Expression of 16 genes that have been linked in the literature to the hypothesized alcohol-breast cancer pathways, were examined. We found that the expression of 9 out of 16 genes under study were associated with cancer survival within the first 4 years of diagnosis. Results from gene set analysis confirmed a significant differential expression of these genes as a whole too. Although alcohol consumption is not analyzed, nor available for this dataset, we believe that further study on these genes could provide important information for clinical recommendations about potential impact of alcohol drinking on breast cancer survival.
Highlights
Breast cancer is the leading cause of cancer-related disease burden in women with an estimated 464,000 deaths worldwide [1]
Three genes were up-regulated (i.e., ITGA5, CBS, and SOD2), while six were down-regulated (i.e, XDH, XRCC1, MTHFR, CYP1B1, XPC, and GSTP1) among individuals who died of breast cancer
We found that the expression of 9 out of 16 alcohol-related genes at the primary tumor were associated with breast cancer four-year survival, after correcting by cancer subtype and age, and 3 of these genes validate in a much smaller dataset
Summary
Breast cancer is the leading cause of cancer-related disease burden in women with an estimated 464,000 deaths worldwide [1]. Cumulative evidence supports a causal role of alcohol intake and breast cancer incidence [2,3,4]. Potential mechanisms include both global and sitespecific changes induced by alcohol intake [5]. It is well possible that the observed relationships are confounded by self selection biases (e.g., “healthy drinker effect”) [6]. Given this context, it is of interest to examine the relationship between genes related to alcohol consumption and breast cancer
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