"Some studies have shown that alcohol consumption increases cancer metastasis," said Gary G. Meadows, Director of the Cancer Prevention & Research Center at Washington State University, "while other studies have shown that alcohol consumption decreases metastasis. Thus, there is a lot more work needed in this area." Meadows, the Dorothy O. Kennedy Distinguished Professor, is also the corresponding author for the study.
For the May ACER study, pathogen-free female mice were divided into a number of study groups, each containing 20 mice. These included nontumor, water-consuming (NW) mice; nontumor, alcohol-consuming (NE) mice; with-tumor, water-consuming (TW) mice; with-tumor, alcohol-consuming (TE) mice; with-tumor, pair-fed mice that had their alcohol calories replaced with maltose-dextrin (T-PF); and with-tumor, pair-fed mice that did not have their alcohol-derived calories replaced with maltose-dextrin. The mice were given water or 20% w/v alcohol in their drinking water for three weeks to six months. Some were then inoculated with melanoma cells subcutaneously into the right dorsal hip. The mice continued to consume water or alcohol, and researchers gathered a variety of biochemical data at various time periods following tumor inoculation, as well as body weight, body water content, tumor weight, and carcass fat content.
"Alcohol consumption caused a loss in body fat in the mice with melanoma," said Meadows, "and this was associated with a decrease in survival of the melanoma-bearing mice. This could be important because cancer patients often lose a lot of weight near the end of life even if they are able to maintain their food intake. It is commonly thought that this weight loss accelerates the progression of the cancer and shortens survival. The weight loss for cancer patients is in body protein as well as body fat. However, the interesting thing about the loss of body weight in our study is that it was from fat, not protein."
"Although often regarded as socially unacceptable, fat serves a useful purpose as energy storage for the body," said Carl Waltenbaugh, professor of immunology at Northwestern University Medical School. "Chronic alcohol consumption increases leptin, a fat-cell (adipocyte) derived hormone that has multiple biological effects, including the ability to change lipid metabolism. Eventually, an alcoholic's body utilizes fat as a primary energy source, resulting in 'wasting' or rapid loss of body weight. Once fat reserves are exhausted, the body must rely more and more upon alcohol as an energy source. At the same time, alcohol depresses immune function, especially natural killer cells that are responsible for tumor cell elimination. This study shows that chronic alcohol consumption shortens cancer survival time for tumor-bearing patients. For alcoholics without known cancer, loss of natural killer cells means that a first line of defense is missing in these individuals, thus increasing their susceptibility to cancer in the future.
Waltenbaugh suggested that future research determine if alcohol presents a confounding factor for more cancers than melanoma; what amount and duration of alcohol consumption causes this effect; whether or not abstinence from alcohol might affect tumor progression/weight loss; and if leptin antagonists might increase chances of survival.
"Other studies have shown that abnormal leptin levels also alter immune function," he said. "Yet alcohol-induced augmentation of leptin is new to science. Elevated leptin levels and diminished immune function in alcohol-consuming individuals suggest a potential cause for increased susceptibility to infection in these individuals." Conversely, he said, this association may also allow scientists to develop ways to protect alcoholics from infection.
Another possibility for future leptin research, according to Meadows, is related to the finding that the tumor-bearing mice lost weight and fat without losing muscle mass (body protein).
"We are planning more studies in the future to see how alcohol influences fat metabolism," said Meadows. "We are very interested in finding the mechanism for the fat loss in the tumor-bearing mice, because this could lead to a new way to promote fat loss in obese people without the accompanying loss in muscle mass during dieting. In particular, we are interested in the effects that alcohol has on leptin, which also has a role in controlling obesity."
Co-authors of the Alcoholism: Clinical & Experimental Research paper included: Nomelí P. Núñez of the Department of Pharmaceutical Sciences, the Pharmacology and Toxicology Graduate Program, and the Cancer Prevention & Research Center at Washington State University; and Patrick A. Carter of the School of Biological Sciences at Washington State University. The study was funded by the National Institute on Alcohol Abuse and Alcoholism.