Study May Explain Why Alcohol Consumption Boosts Breast Cancer Risk
For the first time, scientists have used a laboratory mouse model to mimic the development of human alcohol-induced breast cancer. The results are part of a new study, Chronic Alcohol Consumption Increases Tumor Growth and Amgiogenesis of Breast Cancer in Female Mice.
Background
Alcohol (EtOH) consumption – even moderate – is a well-established risk factor for breast cancer in women. A recent study showed that 60 percent of female breast cancers worldwide were attributable to alcohol consumption. Nevertheless, the mechanisms of alcohol-induced breast cancer are poorly understood.
The definitive biological effects and molecular mechanisms of EtOH on progression and malignancy of breast cancer have not been investigated using a mammalian breast cancer model that mimics the human disease. Scientists have suggested that the possible mechanisms involved include the agitation of estrogen metabolism and response; cell mutation by the EtOH metabolite acetaldehyde; oxidative damage; and one-carbon metabolism pathways through reduced folic acid.
Methodology
To date, there has not been an animal model that faithfully mimics the human disease with respect to characteristics of breast cancer, immunocompetence, and physiologically relevant EtOH intake. The researchers addressed and overcame the obstacles and developed a novel mouse breast cancer model. The model mimics human breast cancer disease in which the estrogen receptor-positive breast adenocarcinoma cells were subcutaneously injected near the pad of the fourth mammary gland of female immunocompetant mice (C57BL/6). The six-week-old female mice were fed with moderate EtOH (one percent in drinking water) for four weeks, the equivalent of two drinks per day in humans. The control mice received regular drinking water only.
In the second week of the experiment, mouse breast cancer cells (5x105 E0771) were injected at cite referenced above. At the end of the experiment, the tumors were isolated to measure tumor size, examine intratumoral microvessel (IM) density via CD 31 immunohistochemistry staining, and assessing VEGF protein levels via ELISA. These steps were taken to determine the effects of EtOH intake in physiologically relevant doses on tumor growth and angiogenesis in mouse breast cancer.
Results
The researchers found:
- that moderate alcohol consumption significantly increased the tumor size of breast cancer in mice, which was a 1.96-fold increase in tumor weight vs. control mice;
- that alcohol intake caused a 1.28-fold increase in tumor microvessel density vs. the control group;
- a significant increase in tissue protein levels of VEGF were found in the tumors of the mice treated with EtOH vs. control group;
- EtOH intake did not cause significant changes in the body weight of the mice.
Conclusions
This study presents the first animal model to confirm that alcohol consumption stimulates tumor growth and malignancy of breast cancer, and reveals some of the mechanisms of alcohol-induced breast cancer. The findings demonstrate that even moderate alcohol consumption significantly stimulates tumor growth of breast cancer and that induction of tumor angiogenesis and VEGF expressions are mechanisms which are associated with the progression of this deadly disease.
Alcohol Increases Hormone Levels, Raising Breast Cancer Risk
Article date: 2001/05/24
Drinking a daily glass of wine may ward off heart problems, but the opposite may be true when it comes to breast cancer. Even small amounts of alcohol may increase hormone levels circulating in the blood that could raise breast cancer risk — especially in postmenopausal women, according to a new study published in the Journal of the National Cancer Institute (Vol. 93, No. 9, 710–715).
Some studies have shown that alcohol consumption may increase the risk of breast cancer, but researchers are unclear as to what exactly causes the increased risk. Researchers led by Joanne Dorgan, MPH, PhD, and her colleagues at the Fox Chase Cancer Center in Philadelphia, investigated whether small amounts of alcohol could boost levels of hormones thought to increase breast cancer risk.
Dorgan’s team studied 51 healthy postmenopausal women who were not taking hormone replacement therapy (HRT), i.e. synthetic estrogens. Each participant went through three 8-week periods in which she consumed 15 or 30 grams of alcohol (the equivalent of one or two drinks) per day, or an alcohol-free drink. At the end of each 8-week period, the researchers measured levels of sex hormones — including estrogen, testosterone, and progesterone — in the women’s blood.
Women who consumed 15 grams of alcohol per day showed a 7.5% increase in a breakdown product of estrogen called estrone sulfate, compared to women not drinking alcohol. Women who consumed 30 grams of alcohol per day showed an even greater increase (10.7%), compared to women not drinking alcohol. Similar increases were seen in another hormone called dehydroepiandrosterone sulfate (DHEAS).
Even One Drink a Day Could Increase Risk
"Our results, suggest that even one drink a day could increase breast cancer risk," Dorgan says, pointing out that hormone levels appeared to increase as the number of drinks increased.
"Most people agree that at higher levels of intake — such as more than three drinks a day — alcohol increases breast cancer risk," says Dorgan. "At lower levels, there is some controversy, which is one of the reasons we did this study," she says.
The study authors note that this is the first study to evaluate under controlled conditions the effects of chronic, moderate alcohol ingestion on levels of serum estrogens and androgens in postmenopausal women.
Dorgan recommends that women might want to consider discussing with their physicians whether they should or should not drink at all. "A physician can advise a woman by taking into account her individual situation," she says.
Cancer and Heart Disease Guidelines Conflict
Michael Thun, MD, vice president of epidemiology and surveillance for the American Cancer Society (ACS), advises "the most important thing to understand is that even at levels of moderate drinking — not exceeding one drink of alcohol daily — the current evidence suggests that there is some increase in breast cancer risk."
"One drink of alcohol a day, however, may reduce the risk of heart disease, so the net effect on a woman’s health depends to a large extent on her age and her risk of breast cancer, and of heart disease," Thun says, noting that alcohol is the one case in which cancer and heart guidelines are in conflict.
"The risk of breast cancer and other cancers increases as alcohol consumption increases," Thun notes. "But after menopause, the reduction in risk of heart attacks and strokes associated with one or two drinks a day is greater than the increase in breast cancer risk for nearly all women," he qualifies.
For the first time, scientists have used a laboratory mouse model to mimic the development of human alcohol-induced breast cancer. The results are part of a new study, Chronic Alcohol Consumption Increases Tumor Growth and Amgiogenesis of Breast Cancer in Female Mice.
Background
Alcohol (EtOH) consumption – even moderate – is a well-established risk factor for breast cancer in women. A recent study showed that 60 percent of female breast cancers worldwide were attributable to alcohol consumption. Nevertheless, the mechanisms of alcohol-induced breast cancer are poorly understood.
The definitive biological effects and molecular mechanisms of EtOH on progression and malignancy of breast cancer have not been investigated using a mammalian breast cancer model that mimics the human disease. Scientists have suggested that the possible mechanisms involved include the agitation of estrogen metabolism and response; cell mutation by the EtOH metabolite acetaldehyde; oxidative damage; and one-carbon metabolism pathways through reduced folic acid.
Methodology
To date, there has not been an animal model that faithfully mimics the human disease with respect to characteristics of breast cancer, immunocompetence, and physiologically relevant EtOH intake. The researchers addressed and overcame the obstacles and developed a novel mouse breast cancer model. The model mimics human breast cancer disease in which the estrogen receptor-positive breast adenocarcinoma cells were subcutaneously injected near the pad of the fourth mammary gland of female immunocompetant mice (C57BL/6). The six-week-old female mice were fed with moderate EtOH (one percent in drinking water) for four weeks, the equivalent of two drinks per day in humans. The control mice received regular drinking water only.
In the second week of the experiment, mouse breast cancer cells (5x105 E0771) were injected at cite referenced above. At the end of the experiment, the tumors were isolated to measure tumor size, examine intratumoral microvessel (IM) density via CD 31 immunohistochemistry staining, and assessing VEGF protein levels via ELISA. These steps were taken to determine the effects of EtOH intake in physiologically relevant doses on tumor growth and angiogenesis in mouse breast cancer.
Results
The researchers found:
- that moderate alcohol consumption significantly increased the tumor size of breast cancer in mice, which was a 1.96-fold increase in tumor weight vs. control mice;
- that alcohol intake caused a 1.28-fold increase in tumor microvessel density vs. the control group;
- a significant increase in tissue protein levels of VEGF were found in the tumors of the mice treated with EtOH vs. control group;
- EtOH intake did not cause significant changes in the body weight of the mice.
Conclusions
This study presents the first animal model to confirm that alcohol consumption stimulates tumor growth and malignancy of breast cancer, and reveals some of the mechanisms of alcohol-induced breast cancer. The findings demonstrate that even moderate alcohol consumption significantly stimulates tumor growth of breast cancer and that induction of tumor angiogenesis and VEGF expressions are mechanisms which are associated with the progression of this deadly disease.
Alcohol Increases Hormone Levels, Raising Breast Cancer Risk
Article date: 2001/05/24
Drinking a daily glass of wine may ward off heart problems, but the opposite may be true when it comes to breast cancer. Even small amounts of alcohol may increase hormone levels circulating in the blood that could raise breast cancer risk — especially in postmenopausal women, according to a new study published in the Journal of the National Cancer Institute (Vol. 93, No. 9, 710–715).
Some studies have shown that alcohol consumption may increase the risk of breast cancer, but researchers are unclear as to what exactly causes the increased risk. Researchers led by Joanne Dorgan, MPH, PhD, and her colleagues at the Fox Chase Cancer Center in Philadelphia, investigated whether small amounts of alcohol could boost levels of hormones thought to increase breast cancer risk.
Dorgan’s team studied 51 healthy postmenopausal women who were not taking hormone replacement therapy (HRT), i.e. synthetic estrogens. Each participant went through three 8-week periods in which she consumed 15 or 30 grams of alcohol (the equivalent of one or two drinks) per day, or an alcohol-free drink. At the end of each 8-week period, the researchers measured levels of sex hormones — including estrogen, testosterone, and progesterone — in the women’s blood.
Women who consumed 15 grams of alcohol per day showed a 7.5% increase in a breakdown product of estrogen called estrone sulfate, compared to women not drinking alcohol. Women who consumed 30 grams of alcohol per day showed an even greater increase (10.7%), compared to women not drinking alcohol. Similar increases were seen in another hormone called dehydroepiandrosterone sulfate (DHEAS).
Even One Drink a Day Could Increase Risk
"Our results, suggest that even one drink a day could increase breast cancer risk," Dorgan says, pointing out that hormone levels appeared to increase as the number of drinks increased.
"Most people agree that at higher levels of intake — such as more than three drinks a day — alcohol increases breast cancer risk," says Dorgan. "At lower levels, there is some controversy, which is one of the reasons we did this study," she says.
The study authors note that this is the first study to evaluate under controlled conditions the effects of chronic, moderate alcohol ingestion on levels of serum estrogens and androgens in postmenopausal women.
Dorgan recommends that women might want to consider discussing with their physicians whether they should or should not drink at all. "A physician can advise a woman by taking into account her individual situation," she says.
Cancer and Heart Disease Guidelines Conflict
Michael Thun, MD, vice president of epidemiology and surveillance for the American Cancer Society (ACS), advises "the most important thing to understand is that even at levels of moderate drinking — not exceeding one drink of alcohol daily — the current evidence suggests that there is some increase in breast cancer risk."
"One drink of alcohol a day, however, may reduce the risk of heart disease, so the net effect on a woman’s health depends to a large extent on her age and her risk of breast cancer, and of heart disease," Thun says, noting that alcohol is the one case in which cancer and heart guidelines are in conflict.
"The risk of breast cancer and other cancers increases as alcohol consumption increases," Thun notes. "But after menopause, the reduction in risk of heart attacks and strokes associated with one or two drinks a day is greater than the increase in breast cancer risk for nearly all women," he qualifies.
