EGFR may couple moderate alcohol consumption to increased breast cancer risk

Abstract

Alcohol consumption is an established risk factor for breast cancer. Nonetheless, the mechanism by which alcohol contributes to breast tumor initiation or progression has yet to be definitively established. Studies using cultured human tumor cell lines have identified signaling molecules that may contribute to the effects of alcohol, including reactive oxygen species and other ethanol metabolites, matrix metalloproteases, the ErbB2/Her2/Neu receptor tyrosine kinase, cytoplasmic protein kinases, adenylate cyclase, E-cadherins, estrogen receptor, and a variety of transcription factors. Emerging data suggest that the epidermal growth factor receptor (EGFR) tyrosine kinase may contribute to breast cancer genesis and progression. Here we integrate these findings and propose three mechanisms by which alcohol contributes to breast cancer. A common feature of these mechanisms is increased EGFR signaling. Finally, we discuss how these mechanisms suggest strategies for addressing the risks associated with alcohol consumption.

Keywords:

• alcohol
• breast cancer risk factor
• EGF receptor
• matrix metalloprotease

Acknowledgments

We acknowledge support from the National Cancer Institute (R01CA114209 to DJR), the US Army Breast Cancer Research Program (DAMD17-00-1-0416 to DJR), the American Cancer Society (IRG-58-006), the Indiana Elks Foundation, the Purdue University Center for Cancer Research, and the Oncological Sciences Center of Purdue University Discovery Park. The authors report no conflicts of interest in this work.