Alcohol and Cancer

Alcohol and Cancer

Critique 039. The role that alcohol drinking may play in the risk of cancer. 17 April 2011

Reference:  Schűtze M, Boeing H, Pischon T, et al, Alcohol attributable burden of incidence of cancer in eight European countries based on results from prospective cohort study.  BMJ 2011; 342:d1584 doi: 10.1136/bmj.d1584 (Published 7 April 2011)

A large group of distinguished scientists have published a very detailed and rather complex paper describing the association between alcohol consumption and cancer.  It is based on data from the EPIC study in Europe, with a mean follow up of 8.8 years for more than 300,000 subjects.  The authors describe an increase in risk of many cancers from alcohol intake, but do not give data permitting the detection of a threshold of intake for an adverse effect on cancer risk.  The investigators conclude that “In western Europe, an important proportion of cases of cancer can be attributable to alcohol consumption, especially consumption higher than the recommended upper limits.”

Members of the Forum were concerned that the authors did not separate moderate consumption from heavy consumption for their main analyses, ignored the demonstrated benefits of moderate drinking on total mortality, and did not point out other environmental influences (such as smoking, diet, obesity, etc.) that often have much larger effects on the risk of many cancers than does alcohol consumption.  The authors make statements such as alcohol has negative effects on total mortality that are not supported by the data presented in their paper, and are contradicted by most large-scale population-based studies.  Overall, while this paper supports the well-known association between heavy drinking and an increased risk of upper aero-digestive and certain other cancers, it adds little information useful for the prevention of most types of cancer.

Critique 018.  Alcohol consumption following diagnosis of early-stage breast cancer may increase risk of recurrence of cancer but not total mortality risk.

14 September 2010

Reference:  Kwan ML, Kushi LH, Weltzien E, Tam EK, Castillo A, Sweeney C, Caan BJ.  Alcohol consumption and breast cancer recurrence and survival among women with early-stage breast cancer: The Life After Cancer Epidemiology Study.  J Clin Oncol 2010;28 (published ahead of print, 10.1200/JCO.2010.29.2730).

In the Life After Cancer Epidemiology (LACE) study, 1,897 participants diagnosed with early-stage breast cancer between 1997 and 2000 and recruited on average 2 years post-breast cancer diagnosis were evaluated for the association between alcohol intake and breast cancer recurrence and death.  The women, who were generally light drinkers, were followed for an average of 7.4 years.  The study reported an increase in risk of breast cancer recurrence and breast cancer death, but no effect on total mortality, to be associated with consumption of 3 to 4 or more drinks per week when compared with women not drinking following their cancer diagnosis.

Previous research has been mixed on this topic.  Almost all large studies have shown no increase in all-cause mortality for women who drink moderately following a diagnosis of breast cancer (as does this study).  As for recurrence of breast cancer, most have shown no increase in risk, although one previous study of women with estrogen-receptor + tumors found an increased risk of a primary cancer developing in the contralateral breast to be associated with alcohol intake of more than 7 drinks per week.

Because of conflicting results among studies on this topic, further research will be needed to determine the extent to which alcohol following a diagnosis of breast cancer may relate to subsequent disease and death.

Critique 016.  Association of alcohol with breast cancer risk varies according to subtype of tumor. 29 August 2010

Reference Li CI, Chlebowski RT, Freiberg M, Johnson KC, Kuller L, Lane D, Lessin L, O’Sullivan MJ, Wactawski-Wende J, Yasmeen S, Prentice R.  Alcohol consumption and risk of postmenopausal breast cancer by subtype: the Women’s Health Initiative Observational Study.  J Natl Cancer Inst 2010 Aug 23. [Epub ahead of print].

Most studies show a slight increase in the risk of breast cancer for women who consume alcohol.  The association is thought to relate to alcohol’s effects on hormones, and alcohol use tends to be more strongly associated with hormonally sensitive breast cancers than tumors not sensitive to hormones.  Few studies have evaluated how alcohol-related risk varies by breast cancer subtype.  In the present study, follow-up data from 87,724 women in the Women’s Health Initiative Observational Study prospective cohort were evaluated for the relation of baseline alcohol consumption with subsequent breast cancer.

A total of 2,944 invasive breast cancer patients were diagnosed during follow up.  In multivariable-adjusted analyses alcohol consumption was associated with an increase in the risk of lobular carcinoma (which makes up approximately 15-20% of breast cancers), but there was not a statistically significant association with the more-common ductal type of carcinoma.  Hormone + cancers showed an association with alcohol intake, but not hormone – cancers.  The findings support the importance of hormonal mechanisms in mediating the relation between alcohol use and breast cancer risk.

Critique 015. Moderate drinking does not appear to increase risk of breast cancer among women with a BRCA gene mutation. 22 August 2010

Reference:  Dennis J, Ghadirian P, Little J, et al:  The Hereditary Breast Cancer Clinical Study Group.  Alcohol consumption and the risk of breast cancer among BRCA1 and BRCA2 mutation carriers.  The Breast 2010; e-pub.

A large study was carried out to assess the effects of alcohol consumption on breast cancer risk among women with a BRCA1 or a BRCA2 gene mutation, both of which markedly increase the risk of breast cancer.  Comparisons were made between women with a gene mutation who had developed invasive breast cancer matched with women with the same gene mutation who had not developed breast cancer.  After a number of appropriate exclusions, there were 1,480 matched pairs with BRCA1 mutations and 445 pairs with BRCA2 mutations.

Data from the study support an earlier report suggesting no increase in breast cancer risk from alcohol intake for women with either gene mutation.  In the previous study on this topic, a slight lowering of breast cancer risk was noted with light drinking among women with the BRCA2 mutation but not among those with the BRCA1 mutation.  In the present study, a possible reduction in risk of breast cancer was seen for moderately drinking women with the BRCA1 mutation, but not the BRCA2 mutation.  Further, in the present study, the reduction is risk of breast cancer was seen only for wine consumers.  While one should not over-interpret epidemiologic data in the absence of identified biologic mechanisms, there have been a very large number of experimental studies showing that certain polyphenols present in wine actively impede the initiation and growth of cancer cells.

Overall, current scientific data suggest that alcohol in moderation does not increase the risk of breast cancer among women with a BRCA mutation, and wine may be somewhat protective.  If this is indeed the case and given the high risk associated with these genetic mutations, it would be important to inform women with such a mutation that moderate alcohol does not appear to increase their risk of breast cancer.

Critique 001. Genetic effects on alcohol metabolism modify the relation of alcohol to breast cancer. 24 April 2010

Reference:  Larsen SB, Vogel U, Christensen J, Hansen RD, Wallin H, Overvad K, Tjønneland A, Tolstrup I.    Interaction between ADH1C Arg272Gln and alcohol intake in relation to breast cancer risk suggests that ethanol is the causal factor in alcohol related breast cancer.  Cancer Letters, 2010, in press.

A study from Germany compared the association between alcohol and breast cancer risk according to genetic variations affecting levels of alcohol dehydrogenase, an enzyme that clears alcohol from the blood stream.  The authors conclude that genetic factors associated with the slow clearance of alcohol are associated with increased risk of breast cancer for drinkers; an increase in cancer risk was not seen for drinkers with genetic factors leading to fast clearance of alcohol.  Such a finding would suggest that alcohol itself is the cause of an increase in breast cancer risk among drinkers.

Unfortunately, some previous studies have shown the opposite, that an increase in breast cancer risk occurs only among women who have genes associated with fast, rather than slow, alcohol metabolism.  Overall, current scientific data indicate that breast cancer’s relation to drinking is not resolved, remaining murky and conflicted, and perhaps overemphasized. This facet of that murkiness is itself also conflicted.  As of now, it is unclear the degree to which genes affecting alcohol dehydrogenase modify the association between alcohol and the risk of breast cancer and other diseases.