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Adapted from the NCI Cancer Bulletin, vol. 5/no. 9, April 29, 2008 (see the current issue).
While the potential health benefits of moderate alcohol consumption have garnered a lot of public attention, alcohol's impact on cancer risk has received much less. Epidemiological studies have consistently found that heavy drinking can increase the risk of liver, head and neck, and esophageal cancers, and even moderate drinking has been shown to increase the risk of breast cancer.
At the 2008 American Association for Cancer Research (AACR) annual meeting in San Diego, two new studies were presented that shed additional light on the alcohol-breast cancer connection, including one study that linked alcohol consumption with a significantly increased risk of the most common type of breast cancer.
Even though these studies grabbed headlines, researchers stress that important questions remain unanswered, such as which women who drink are at greatest risk, and what biological mechanism(s) alcohol might trigger to cause breast cancer. In short, researchers are still accumulating evidence that can form the basis for personalized clinical recommendations.
Nevertheless, some recommendations have already been made. As part of a far larger report on cancer prevention released last year, a consensus panel formed by the American Institute for Cancer Research (AICR) concluded: "The evidence on cancer justifies a recommendation not to drink alcoholic drinks."
The AICR report also acknowledged, however, the consistent findings that moderate alcohol consumption can protect against heart disease, and offered that, if individuals choose to drink, women should limit their consumption to one alcoholic beverage per day and men to two.
But even a highly consistent association between alcohol intake and breast cancer risk "is not the same as saying causality has been proven," says Dr. Arthur Schatzkin, chief of the Nutritional Epidemiology Branch in the National Cancer Institute's (NCI) Division of Cancer Epidemiology and Genetics. The same, he adds, holds true for the protection against heart disease.
"The breast cancer risks involved with alcohol are indeed modest; nothing like the magnitude of the risks between smoking and lung cancer or HPV and cervical cancer," Dr. Schatzkin continues. "So it's difficult to be absolutely certain from the available studies that it's not some other biologic or behavioral factors associated with moderate drinking that are the real etiologic agents in breast cancer."
The important point, he stresses, is that "Drinking alcohol is an entirely avoidable risk factor," especially for women with established risks like a family history of breast cancer.
Studies dating back to the 1920s show that alcohol consumption and mortality risk are represented by a J-shaped curve: Risk of death is somewhat elevated in teetotalers, dips for moderate drinkers, and then climbs steadily as consumption increases.
According to long-term studies performed by Dr. Arthur Klatsky and colleagues at Kaiser Permanente in Oakland, CA, the vast bulk of the benefit of light-to-moderate alcohol consumption is due to an apparent protective effect against cardiovascular disease, primarily in middle-aged people.
Incidence data presented by NCI researchers at the AACR meeting were somewhat consistent with a J-curve, at least in terms of excessive alcohol consumption. Based on an analysis of more than 180,000 women in the NIH-AARP Diet and Health Study, they found that women who consumed three or more alcoholic drinks a day had more than a 50-percent increased risk of ER+/PR+ breast cancer, while women who drank smaller amounts also had an elevated risk, regardless of alcohol type.
The results, Dr. Klatsky notes, are mostly consistent with data from his studies and support the hypothesis that alcohol may increase breast cancer risk via an effect on estrogen. However, the results are not entirely consistent and highlight the difficulty in establishing a risk "threshold," Dr. Klatsky explains.
"Our data show that women who report having just several drinks a week don't have an increased [breast cancer] risk, and the risk begins somewhere between that and two drinks per day," he says.
In addition to the interplay between alcohol and estrogen, research has focused on several genes that code for the enzyme alcohol dehydrogenase (ADH), which is involved in alcohol metabolism. ADH initiates the breakdown of alcohol into acetaldehyde, ethanol's first metabolite, which is carcinogenic in animal models.
At the AACR meeting, researchers from Georgetown University's Lombardi Comprehensive Cancer Center and the State University of New York at Buffalo, using data from the Western New York Exposure and Breast Cancer Study, reported finding an increased breast cancer risk among postmenopausal women
who drank and had variations in a gene that codes for ADH. The more the women reported drinking, the greater their risk.
"This is what we're really trying to get at now," says Lombardi's Deputy Director, Dr. Peter Shields, who co-led the study. "We're assuming that there are certain genetic susceptibilities. There's some evidence for it, but not enough studies to say that, for women who drink, certain genes put you at increased risk of breast cancer."
But other molecular players may
be at work. Dr. Shields' lab has received funding from the Department of Defense to take a more systematic look at four potential causal mechanisms suggested by previous studies. These include the alcohol-estrogen link and the role of acetaldehyde, as well as alcohol-induced oxidative damage and disruption of folic acid pathways.
"We want to take this type of
beverage that many women are
going to drink," Dr. Shields says,
"and figure out when they are really putting themselves at risk."
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