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New clues may link hereditary cancer genes to increased risk of cancer from alcohol
Date:1/23/2014

differ by 10-fold or larger," says Kern.

The scientists found that BRCA2 and PALB2-mutant cell lines exposed to acetaldehyde had up to 25 times more growth reduction when compared with related cells lacking these mutations. The significant reduction in cell growth indicates that these cell lines, which lack the two genes, are more susceptible to the DNA damage caused by acetaldehyde, say the scientists. They suggest that the DNA-damaging effects of acetaldehyde exposure in people lacking these genes may accelerate cancer growth.

Kern and his team estimated that the BRCA2 and PALB2 genes, when they function normally, protect cells against up to 96 percent of the toxicity associated with acetaldehyde. Results of the experiments are published in the January 2014 issue of the American Journal of Pathology.

Kern says that the acetaldehyde model could, theoretically, be used to develop drugs that kill cancer cells, as well as to alter cancer risk. They found that cell lines with mutations in PALB2 were up to 20 percent more sensitive to chemotherapy agents, such as cisplatin, that work by breaking down DNA, compared with anticancer drugs that work in other ways.

When the genes function correctly, BRCA2 and PALB2 bind to each other to repair DNA damage. Mutations in the genes disable their DNArepairing capability and make carriers more susceptible to cancer, the researchers say.

"BRCA2 and PALB2 may have evolved over time to repair or protect us from acetaldehyde damage," says Kern. "In most people, the genes function well and we're equipped to handle most of our exposure to acetaldehyde, but patients or carriers with mutations in these genes could face a higher risk of cancers with high exposure to alcohol or acetaldehyde-containing foods."

Kerns says that there is a possibility acetaldehyde leaves a signature of damage in cells. He adds that scientists may have been overlooking the role of acetaldehyde in d
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Contact: Vanessa Wasta
wasta@jhmi.edu
410-614-2916
Johns Hopkins Medicine
Source:Eurekalert

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