Critique 072: Obesity may modify the association between alcohol consumption and the risk of colorectal cancer — 23 February 2012

Zhao J, Zhu Y, Wang PP, et al.  Interaction between alcohol drinking and obesity in relation to colorectal cancer risk: a case-control study in Newfoundland and Labrador, CanadaBMC Public Health 2012, 12:94 doi:10.1186/1471-2458-12-94

Authors’ Abstract

Background:  While substantive epidemiological literature suggests that alcohol drinking and obesity are potential risk factors of colorectal cancer (CRC), the possible interaction between the two has not been adequately explored.  We used a case-control study to examine if alcohol drinking is associated with an increased risk of CRC and if such risk differs in people with and without obesity.

Methods:  Newly diagnosed CRC cases were identified between 1999 and 2003 in Newfoundland and Labrador (NL).  Cases were frequency-matched by age and sex with controls selected using random digit dialing.  Cases (702) and controls (717) completed self-administered questionnaires assessing health and lifestyle variables.  Estimates of alcohol intake included types of beverage, years of drinking, and average number of alcohol drinks per day.  Odds ratios were estimated to investigate the associations of alcohol independently and when stratified by obesity status on the risk of CRC.

Results:  Among obese participants (BMI ≥ 30), alcohol was associated with higher risk of CRC (OR: 2.2; 95% CI: 1.2–4.0) relative to the non-alcohol category.  Among obese individuals, 3 or more different types of drinks were associated with a 3.4-fold higher risk of CRC relative to non-drinkers.  The risk of CRC also increased with drinking years and drinks daily among obese participants.  However, no increased risk was observed in people without obesity.

Conclusion:  The effect of alcohol of drinking on CRC seems to be modified by obesity.

Forum Comments

Background:  Colorectal cancer (CRC) is a very common type of cancer among both men and women.  Parkin et al1 recently reported that in the United Kingdom, 4.6% of total cancer in men and 3.3% in women can be due to alcohol consumption; for CRC, their estimate of the population-attributable-risk due to alcohol consumption was 12%.  However, in epidemiologic studies overall, data are inconclusive as to whether, or to what degree, alcohol consumption relates to risk.2-6  Given that the majority of the population in western countries consumes alcohol, and that CRC is a very common cancer, it is especially important to have a clear picture of  such an association. 

The present study was conducted in Newfoundland/Labrador, a region with greater obesity, more alcohol intake, and higher rates of CRC than other parts of Canada.  While the present analysis is a case-control study, rather than a cohort study, its demonstration of a potentially modifying effect of obesity on the relation between alcohol intake and such cancer has relevance.

A recently reported analysis on two large cohort studies found a significant increase in CRC risk only for subjects consuming larger amounts of alcohol who had a positive family history of such cancer.7  The present study does not report specifically whether or not family history modified the relation of alcohol and cancer among obese subjects.

Specific comments on paper:  The authors are somewhat confusing in terms of definitions of who is, and who is not, a “drinker.”  The paper includes as “non-drinkers” individuals who do not drink as well as light drinkers who drank less than one drink per day, while “drinker” was defined as drinkers who ever consumed any alcoholic beverage once a week for 6 months or longer.  While this study had reasonable estimates of long-term alcohol intake from questionnaires, only 60% of cases and 45% of controls recruited by telephone contact provided data.  However, data were collected on key known potential confounders, such as age, family history of CRC, education, smoking, intake of fruits and vegetables, and aspirin use. 

The authors did not report on folate intake, and no serum levels of folate were available.  The intake of alcohol has been shown to interact with folate in the association between drinking and other cancers.8  It would be interesting to analyze more completely whether, and how, diet interacts with obesity and alcohol consumption in affecting the risk of CRC.  In a previous study,9 drinkers in Hawaii consumed more meat, pickled vegetables, and dried fish, and less fruits, fruit juices, and raw vegetables than did abstainers; these dietary behaviors have been associated with several types of cancer.10  The results of the study would suggest a re-analysis of data from other cohort studies with data on alcohol use, obesity and risk of CRC (such as Le Marchand et al11) that have no separate analyses of obesity status and cancer risk.

One Forum reviewer thought that we should not overlook the strong scientific evidence that moderate alcohol consumption is associated with a considerable decrease in the risk of cardiovascular disease, which currently claims more lives each year than all cancers, chronic respiratory disease, and accidents combined.12  Further, moderate alcohol consumption is consistently associated with greater longevity of life.  On the other hand, the results of this study could be important.  If the findings of the study are validated, moderate drinkers should be sure to obtain their regular screening colonoscopy, as this simple procedure generally detects precancerous lesions years ahead of malignant transformation.

References from Forum comments

1.  Parkin DM, Boyd L, Walker LC.  The fraction of cancer attributable to lifestyle and environmental factors in the UK in 2010. Summary and conclusions.  Br J Cancer 2011;105:S77 – S81.

2.  Shimizu N, Nagata C, Shimizu H, Kametani M, Takeyama N, Ohnuma T, et al.  Height, weight, and alcohol consumption in relation to the risk of colorectal cancer in Japan: a  prospective study.  Br J Cancer 2003;88:1038–1043.

3.  Wei EK, Giovannucci E, Wu K, Rosner B, Fuchs CS, Willett WC, et al.  Comparison of risk factors for colon and rectal cancer.  Int J Cancer 2004;108:433–442.

4. Su LJ, Arab L.  Alcohol consumption and risk of colon cancer: evidence from the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study.  Nutr Cancer 2004;50:111–119.

5.  Fedirko V, Tramacere I, Bagnardi V, Rota M, Scotti L, Islami F, et al.  Alcohol drinking and colorectal cancer risk: an overall and dose-response meta-analysis of published studies.  Ann Oncol 2011;22:1958–1972.

6. Crockett SD, Long MD, Dellon ES, Martin CF, Galanko JA, Sandler RS.  Inverse relationship between moderate alcohol intake and rectal cancer: analysis of the North Carolina Colon Cancer Study.  Dis Colon Rectum 2011;54:887–894.

7  Cho E, Lee JE, Rimm EB, Fuchs CS, Giovannucci EL.  Alcohol consumption and the risk of colon cancer by family history of colorectal cancer.  Am J Clin Nutr 2012;95:413–419.

8.  Rimm EB, Willett WC, Hu FB, et al.  Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women.  JAMA 1998;27:359-364.

9.  Le Marchand L, Kolonel LN, Hankin JH, Yoshizawa CN.  Relationship of alcohol consumption to diet: a population-based study in Hawaii.  Am J Clin Nutr 1989;49:567-572.

10.  Committee on Diet, Nutrition and Cancer, National Research Council.  Diet, nutrition and cancer.  Washington, DC: National Academy Press, 1982.

11.  Le Marchand L, Wilkens LR, Kolonel LN, et al.  Associations of sedentary lifestyle, obesity, smoking, alcohol use, and diabetes with the risk of colorectal cancer. Cancer Research 1997;57:4787-4794.

12.  Roger VL, Go AS, Lloyd-Jones DM, et al.  Heart disease and stroke statistics – 2012 Update.  A report from the American Heart Association.  Circulation 2011; DOI: 10.1161/CIR.0b013e31823ac046  (available at

Forum Summary

A case-control study from Newfound/Labrador has reported that greater alcohol intake may increase the risk of colorectal cancer among obese subjects, but not among non-obese subjects.  This is not a particularly large study, and only 45-60% of subjects who were recruited by telephone ended up providing data.  Further, it is a case-control comparison, rather than a cohort analysis, making bias in the results more likely. 

In this study, there was no relation of alcohol with the risk of CRC when considering the entire population.  However, when subjects were stratified by BMI (<30 versus ≥ 30), the data indicate an increase in CRC risk for obese subjects who were “drinkers” (OR=2.2, 95% CI 1.2-4.0), especially among subjects reporting 5 or more drinks/daily (OR=3.7, CI 1.5-9.0).  On the other hand, even among obese subjects there was not a clear dose-response effect noted, i.e., there was not a step-wise increase in CRC risk with greater number of drinks/day  For example, the odds ratio (OR) was 2.3 times that of non-drinkers for obese subjects reporting 1-2 drinks/daily and 1.3 for those reporting 3-4 drinks/daily. 

It will be interesting to determine if other studies show that there is modification of the association between alcohol intake and colorectal cancer by obesity.  If such is the case, it could help understand some of the mechanisms for the development of cancer and provide better guidelines for screening for CRC. 

                                                                                *                      *                      *

Comments on this paper were provided by the following members of the International Scientific Forum on Alcohol Research:

Andrew L. Waterhouse, PhD, Marvin Sands Professor, Department of Viticulture and Enology, University of California, Davis; Davis, CA, USA

Harvey Finkel, MD, Hematology/Oncology, Boston University Medical Center, Boston, MA, USA

Tedd Goldfinger, DO, FACC, Desert Cardiology of Tucson Heart Center, Dept. of Cardiology, University of Arizona School of Medicine, Tucson, Arizona, USA

Arne Svilaas, MD, PhD, general practice and lipidology, Oslo University Hospital, Oslo, Norway

R. Curtis Ellison, MD, Section of Preventive Medicine & Epidemiology, Boston University School of Medicine, Boston, MA, USA

Erik Skovenborg, MD, Scandinavian Medical Alcohol Board, Practitioner, Aarhus, Denmark