A research team presented findings that they say may finally explain the link between alcohol consumption and breast cancer. "Cells have different mechanisms1 to remove toxic2 substances, such as ethanol(乙醇) , the chemical name for alcohol, that represent a potential risk to them," explains María de Lourdes Rodríguez-Fragoso, professor of pharmacology and toxicology at the Universidad Autonoma del Estado de Morelos in Mexico. "Unfortunately, sometimes these mechanisms produce other toxic substances, including some that are associated with the development of different types of cancer."
Rodríguez-Fragoso presented her group's work at the annual meeting of the American Society for Biochemistry and Molecular3 Biology, held in conjunction with the Experimental Biology 2012 conference in San Diego on April 23.
Alcohol consumption has long been established as a risk factor for breast cancer. But finding the direct link that makes it so has so far proved elusive4. Now, Rodríguez-Fragoso and her collaborators think that they have found the answer, a protein called CYP2E1.
"We knew that CYP2E1 could break down ethanol and that doing so created unstable5, highly reactive chemicals known as free radicals7," she says. Working with researcher Scott Burchiel and his group at the University of New Mexico, Rodríguez-Fragoso's team had previously8 found that free radicals were associated with activation9 of cellular10 mechanisms that lead to tumor11 development. "The question then was, does having more CYP2E1 make you more susceptible12 to ethanol-induced toxicity13, thereby14 increasing your risk of developing cancer?"
CYP2E1 is found in breast cells known as mammary epithelial cells(上皮细胞) , which are also where most breast cancers originate, suggesting to the researchers that CYP2E1 may be involved in breast cancer development. To test this hypothesis, the researchers administered ethanol to separate cultures of mammary epithelial cells that had varying levels of CYP2E1. Cells that expressed low levels of CYP2E1 were mostly immune to the effects of the ethanol treatment; however, cells with increased amounts of CYP2E1 protein were greatly affected15, suggesting that women with higher expression levels of the protein would show similar responses.
Significantly, points out Rodríguez-Fragoso, "our results showed that ethanol-treated human mammary cells had an increase in free radical6 production, oxidative stress(氧化应激) and the activation of cellular mechanisms that cause cells to increase their proliferation rate," all hallmarks of cancer. "So if you are a woman who naturally expresses higher levels of CYP2E1 and you consume alcohol, you would be at a greater risk for developing breast cancer than a woman who expresses lower amounts of CYP2E1," she explains.