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Study Provides Clues to Alcohol's Cancer Connection

Alcohol Stimulates Blood Vessel Development

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Updated December 14, 2004

For the first time scientists have demonstrated a model that may explain how alcohol stimulates tumor growth.

Their study, published in the January 15, 2005 issue of Cancer, says alcohol fuels the production of a growth factor that stimulates blood vessel development in tumors, and that chronic ethanol increased tumor size and levels of the angiogenic factor and levels of the angiogenic factor and vascular endothelial growth factor (VEGF) in an experimental model.

For almost a hundred years mounting epidemiological evidence has linked alcohol use to an increased risk of cancers of the stomach, esophagus, liver, breast, and colon. Researchers have never developed an adequate model to explain how ethanol or a metabolite of ethanol may cause cancer.

Hypotheses abound, and include such diverse theories as acetaldehyde carcinogenicity, dietary imbalances, and impaired nutrient metabolism and detoxification due to alcohol consumption, activation of precancerous enzymes, and suppression of the immune system.

Recent data in a cellular model has demonstrated that ethanol increases cellular production of VEGF, an important signaling protein in blood vessel growth, particularly in tumors. Jian-Wei Gu. M.D. from the University of Mississippi Medical Center and colleagues further investigated the possible mechanism between ethanol-induced blood vessel growth and VEGF using a chick embryo model.

The investigators exposed chick embryos inoculated with fibrosarcoma cells to saline or physiologically relevant levels of ethanol for nine days.

8 Times More Cancer Cells

The investigators found that compared to the saline control group, the embryos exposed to ethanol experienced increases in tumor size, tumor blood vessel density, cancer cell infiltration of blood vessels, and VEGF levels. Tumor volume and intratumoral vascular volume more than doubled.

There was also a significant dose-related increase in VEGF mRNA and protein expression in tumors and cultured cells. Embryos exposed to ethanol had more than eight times the level of cancer cell invasion of blood vessels compared to the control group.

The authors say their findings "support the hypothesis that the induction of angiogenesis and VEGF expression by ethanol represent an important mechanism of cancer progression associated with alcoholic beverage consumption."

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