Home > Alcohol consumption and cancer risk: understanding possible causal mechanisms for breast and colorectal cancers.

Oyesanmi, Olu and Snyder, David and Sullivan, Nancy and Reston, James and Treadwell, Jonathan and Schoelles, Karen M (2010) Alcohol consumption and cancer risk: understanding possible causal mechanisms for breast and colorectal cancers. Rockville, MD: Agency for Healthcare Research and Quality. AHRQ Publication No. 11-E003.

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Objectives: The purpose of this report is to systematically examine the possible causal mechanism(s) that may explain the association between alcohol (ethanol) consumption and the risk of developing breast and colorectal cancers.

Data Sources: We searched 11 external databases, including PubMed® and Embase, for studies on possible mechanisms. These searches used Medical Subject Headings and free text words to identify relevant evidence.

Review Methods: Two reviewers independently screened search results, selected studies to be included, and reviewed each trial for inclusion. We manually examined the bibliographies of included studies, scanned the content of new issues of selected journals, and reviewed relevant gray literature for potential additional articles.

Breast Cancer. Five human and 15 animal studies identified in our searches point to a connection between alcohol intake and changes in important metabolic pathways that when altered may increase the risk of developing breast cancer. Alterations in blood hormone levels, especially elevated estrogen-related hormones, have been reported in humans. Several cell line studies suggest that the estrogen receptor pathways may be altered by ethanol. Increased estrogen levels may increase the risk of breast cancer through increases in cell proliferation and alterations in estrogen receptors. Human studies have also suggested a connection with prolactin and with biomarkers of oxidative stress. Of 15 animal studies, six reported increased mammary tumorigenesis (four administered a co-carcinogen and two did not). Other animal studies reported conversion of ethanol to acetaldehyde in mammary tissue as having a significant effect on the progression of tumor development.

Fifteen cell line studies suggested the following mechanisms:
• Increased hormonal receptor levels.
• Increased cell proliferation.
• A direct stimulatory effect.
• DNA adduct formation.
• Increase cyclic adenosine monophosphate (camp).
• Change in potassium channels.
• Modulation of gene expression.

Colorectal Cancer. One human tissue study, 19 animal studies (of which 12 administered a co-carcinogen and seven did not), and 10 cell line studies indicate that ethanol and acetaldehyde may alter metabolic pathways and cell structures that increase the risk of developing colon cancer. Exposure of human colonic biopsies to acetaldehyde suggests that acetaldehyde disrupts epithelial tight junctions.

Among 19 animal studies the mechanisms considered included:
• Mucosal damage after ethanol consumption.
• Increased degradation of folate.
• Stimulation of rectal carcinogenesis.
• Increased cell proliferation.
• Increased effect of carcinogens.
Ten cell line studies suggested:
• Folate uptake modulation.
• Tumor necrosis factor modulation.
• Inflammation and cell death.
• DNA adduct formation.
• Cell differentiation.
• Modulation of gene expression.

One study used a combination of animal and cell line and suggested intestinal cell proliferation and disruption of cellular signals as possible mechanisms.

Conclusions: Based on our systematic review of the literature, many potential mechanisms by which alcohol may influence the development of breast or colorectal cancers have been explored but the exact connection or connections remain unclear. The evidence points in several directions but the importance of any one mechanism is not apparent at this time.

Item Type
Publication Type
International, Report, Review
Drug Type
Intervention Type
Harm reduction
November 2010
Identification #
AHRQ Publication No. 11-E003
151 p.
Agency for Healthcare Research and Quality
Place of Publication
Rockville, MD
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