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. Annals of Oncology 22: 1958–1972, 2011, doi:10.1093/annonc/mdq653
Background: The International Agency for Research on Cancer (IARC) concluded that alcohol consumption is related to colorectal cancer (CRC). However, several issues remain unresolved, including quantification of the association for light (≤ 1 drink/day) and moderate (2–3 drinks/day) alcohol drinking, investigation of the dose–response relationship, and potential heterogeneity of effects by sex, colorectal site, and geographical region.
Methods: Twenty-seven cohort and 34 case–control studies presenting results for at least three categories of alcohol intake were identified from a PubMed search of articles published before May 2010. The summary relative risks (RRs) were estimated by the random effects model. Second-order fractional polynomials and random effects metaregression models were used for modeling the dose–risk relation.
Results: The RRs were 1.21 [95% confidence interval (CI) 1.13–1.28] for moderate and 1.52 (95% CI 1.27–1.81) for heavy (≥ 4 drinks/day) alcohol drinking. The RR for moderate drinkers, compared with non-/occasional drinkers, was stronger for men (RR = 1.24, 95% CI 1.13–1.37) than for women (RR = 1.08, 95% CI 1.03–1.13; Pheterogeneity = 0.02). For heavy drinkers, the association was stronger in Asian studies (RR = 1.81, 95% CI 1.33–2.46; Pheterogeneity = 0.04). The dose–risk analysis estimated RRs of 1.07 (95% CI 1.04–1.10), 1.38 (95% CI 1.28–1.50), and 1.82 (95% CI 1.41–2.35) for 10, 50, and 100 g/day of alcohol, respectively.
Conclusions: This meta-analysis provides strong evidence for an association between alcohol drinking of >1 drink/day and colorectal cancer risk.
Forum members considered this to be a well-done analysis, using appropriate statistical methodology. However, they had three major concerns that may limit somewhat the implications of the study:
1. The definition of “moderate” drinking: Defining up to 49.9 grams of alcohol (up to 4 typical drinks) per day as “moderate drinking” is not in line with most national guidelines. It would have been more informative if results were presented by 1 to 2 drinks/day, 2 to 3 drinks/day, etc., since most guidelines consider more than 12 to 15 g/day for women and more than 24 to 30 g/day for men as exceeding moderate or sensible levels. One reviewer pointed out that “A quick read of the abstract gives the impression that any amount of alcohol leads to higher risk of colorectal cancers. In the text and tables, however, the risk of these cancers for drinkers averaging up to one drink/day is the same as that of non-drinkers.”
2. The failure to describe results by type of beverage: For many health outcomes, consumers of wine, or sometimes wine/beer, tend to have very different results than do consumers of other beverages. The authors state that few studies report differences by type of beverage, but do not give results for those that did provide such data. As one Forum reviewer stated: “The real question to be answered, and of great interest to the epidemiologist and clinician alike, is whether we can differentiate between alcohol types and cancer risk. The authors state that more that mild drinking may be associated with other unhealthy lifestyle factors such as poor diet, sedentary lifestyle, and smoking; however, most studies have shown that consumers of wine have better lifestyle factors than do non-drinkers.” Future studies should focus on the type of beverage consumed.
3. No data on pattern of drinking: It is increasingly clear that regular moderate drinking has many health benefits, and fewer adverse effects, than consumption on only one or two days per week, or binge drinking. Again, it would have been helpful for the authors to indicate any differences they found among the studies that did provide such information.
In addition, a Forum reviewer pointed out that the authors state in their introduction that “It has been estimated that in 2002, 5.1% and 1.3% of all cancer deaths were attributable to alcohol drinking worldwide in men and women, respectively.” It would have been useful for the authors to use their data to estimate the disease burden generated by alcohol when consumed by what most studies and agencies consider to be “moderate” or “sensible” drinking.
Several Forum reviewers raised questions about using meta-analyses to reach answers upon which to base clinical decisions. One stated: “Meta-analysis is a retrospective tool, and either positive or negative changes of RR risk of less than 2.0 in the retrospective analysis of heterogeneous papers can only suggest the characteristics of prospective investigations that take into consideration other risk factors and other clinical outcomes.”
A meta-analysis of case-control and cohort studies on the association of alcohol consumption with colorectal cancer was carried out, based on 22 studies from Asia, 2 from Australia, 13 from Western Europe, and 24 from North America. The paper provides evidence that alcohol, at least at higher levels of consumption, is associated with an increase in the risk of colorectal cancer. Overall, there was no increase in the risk for consumers reporting an average intake of up to 1 drink per day, but a modest increase (of 21%) for what the authors defined as “moderate drinking” (averaging up to 49.9 g of alcohol, or about 4 typical drinks, per day). The increase in risk was greater (52%) for consumers of 50 or more grams of alcohol per day.
Forum reviewers thought that this was, in general, a very well-done study that used appropriate statistical techniques for meta-analysis. There were key concerns, however, including the following: (1) the authors’ definition of “moderate drinking” extended well above the usual recommended limits for sensible drinking; effects of consumption in categories of 1 to 2 drinks/day, 2 to 3 drinks/day, etc., were not given; (2) no results were provided according to type of beverage even though many previous studies have shown differences between health effects for consumers of wine, or wine/beer, and other beverages; and (3) no data were available on the pattern of drinking. Many studies have shown that regular, moderate drinking on most days of the week has very different health outcomes than drinking only on week-ends or binge drinking.
Despite these concerns, Forum members agreed that current data indicate that alcohol intake, especially heavier drinking, is associated with an increase in the risk of colorectal cancers. Future studies are needed to help determine if there is a threshold level of alcohol that increases the risk, if there are differences by type of beverage, and if the pattern of drinking (regular versus binge drinking) affects the risk.
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Comments on this critique by the International Scientific Forum on Alcohol Research were provided by the following members:
R. Curtis Ellison, MD, Section of Preventive Medicine & Epidemiology, Boston University School of Medicine, Boston, MA, 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
Francesco Orlandi, MD, Department of Gastroenterology, Università degli Studi di Ancona, Italy
Creina Stockley, clinical pharmacology, Health and Regulatory Information Manager, Australian Wine Research Institute, Glen Osmond, South Australia, Australia
Arne Svilaas, MD, PhD, general practice and lipidology, Oslo University Hospital, Oslo, Norway
Gordon Troup, MSc, DSc, School of Physics, Monash University, Victoria, Australia
Fulvio Ursini, MD, Dept. of Biological Chemistry, University of Padova, Padova, Italy
Andrew L. Waterhouse, PhD, Marvin Sands Professor, Department of Viticulture and Enology, University of California, Davis, USA