Critique 208: A statement on alcohol and cancer that ignores the net health effects of moderate drinking, such as increasing longevity of life — 16 November 2017

LoConte NK, Brewster AM, Kaur JS, Merrill JK, Alberg AJ. Alcohol and Cancer: A Statement of the American Society of Clinical Oncology.  J Clin Oncol 2017;35:pre-publication.  DOI: https://doi.org/10.1200/JCO.2017. 76.1155

 Authors’ Abstract

Alcohol drinking is an established risk factor for several malignancies, and it is a potentially modifiable risk factor for cancer. The Cancer Prevention Committee of the American Society of Clinical Oncology (ASCO) believes that a proactive stance by the Society to minimize excessive exposure to alcohol has important implications for cancer prevention. In addition, the role of alcohol drinking on outcomes in patients with cancer is in its formative stages, and ASCO can play a key role by generating a research agenda. Also, ASCO could provide needed leadership in the cancer community on this issue.

In the issuance of this statement, ASCO joins a growing number of international organizations by establishing a platform to support effective public health strategies in this area. The goals of this statement are to:

• Promote public education about the risks between alcohol abuse and certain types of cancer;
• Support policy efforts to reduce the risk of cancer through evidence-based strategies that prevent excessive use of alcohol;Provide education to oncology providers about the influence of excessive alcohol use and cancer risks and treatment complications, including clarification of conflicting evidence; and
• Identify areas of needed research regarding the relationship between alcohol use and cancer risk and outcomes.

Forum Comments

There are a number of problems with this publication. The authors show increases even from light drinking for several cancers (oral cavity and pharynx, squamous cell carcinoma of the esophagus, and breast cancer).  Forum member Ellison stated: “I am not sure that the associations between light drinking and upper aero-digestive tract cancers have been clearly shown, although most studies suggest a slight increase for breast cancer even among light drinkers.  However, the authors do not define the limits for the categories of light, moderate, or heavy drinking.  And, obviously, they do not bring up the risk of under-reporting of alcohol when showing increased risk of certain cancers from light drinking, the importance of which has been illustrated well by Klatsky et al.”

Reviewer De Gaetano stressed that “A major problem in this publication is that the authors continually mix effects of light to moderate drinking with heavy drinking or alcohol abuse, not clearly delimiting differences in health effects. When they simply say ‘alcohol’ most often they refer to heavy consumption.”

The authors bring up the question of different effects according to the type of beverage consumed, but then give only one reference (from IARC) saying that the effects are the same for all beverages. They ignore a much larger group of studies showing differential effects, especially between wine and spirits consumption (as summarized in a meta-analysis by Costanzo et al, 2011).

The authors state: “Measures of adverse consequences of alcohol tend to concentrate more among those of a lower socioeconomic status. A disproportionate share of the overall burden of cancer occurs in those of a lower socioeconomic status.”  Then, they tend to dismiss this association by stating: “however, this remains a relatively unexplored topic” (despite extensive recent studies confirming this association by Lee et al, Larsson et al, and Katikireddi et al).

Similarly, the authors of this paper mention the importance of the pattern of drinking, but do not provide a discussion of binge versus regular moderate intake, which are the most important differences in drinking patterns associated with adverse effects. Instead, they have a long discussion of “higher rates are seen in sexual and gender minority populations (ie, lesbian, gay, bisexual, transgender, and intersex)” and talk about “increased alcohol use and abuse among lesbian, gay, and bisexual youth.”

Marked selectivity in the references cited: Forum member Ellison stated: “In the text, the authors mention many of the potentially beneficial health effects of moderate drinking, but then find a paper to discredit the association; they are very selective in their references, rather than presenting data based on the majority of studies available on the topic.”  Reviewer Stockley agreed:  “It was frustrating that data dismissing an association between light to moderate alcohol consumption and cardio-protection is selectively cited rather than the voluminous data supporting a j-shaped relationship between alcohol consumption, cardiovascular disease, diabetes and all-cause mortality.”

Other Forum members agreed that the authors of this paper were extremely selective in choosing the references to support their conclusions. While most of the increases in risk of specific cancers are based on reasonable studies, the authors fail to mention meta-analyses/large studies (e.g., Cao et al, and most recently that of Choi et al) other than the single one they quote that fails to support many of the associations described, especially between light drinking and certain cancers.

Multiple factors affecting the risk of cancer: Reviewer van Velden stated: “To view alcohol consumption reductionalistically, without taking into consideration other lifestyle habits, we cannot come to realistic conclusions.  Empirical science must take a systematic view on this issue to exclude other confounding variables that may influence the results.  The etiology of cancer does not depend on diet (or alcohol) alone, but genetic factors interacting with environmental influences and increased longevity are major drivers for cancer.  We must have a holistic view on cancer causation and cancer prevention.  The question is not always why we get cancer, but why our resistance to cancer dropped.”

Reviewer Estruch pointed out the importance of analyzing the effects of alcohol intake within the umbrella of the dietary pattern of participants included in cohort studies. “In our experience the effects of alcohol intake (even in moderate doses) on cancer depend on the dietary pattern. Subjects who consume a traditional Mediterranean diet, even when consuming moderate amounts of alcohol (mainly wine), reduce the incidence of cancer and specially cancer mortality, whereas those who drink moderately but follow an unhealthy diet, increase the incidence of cancer.”

Forum member Estruch continued: “In addition, I would also add that consumption of healthy foods varies according to countries. Thus, participants in the UK EPIC-Oxford study (health conscious, large proportion vegetarian and vegan) had higher consumptions of vegetables, legumes, fruits, and vegetable oils than the general UK population, but their intake was substantially lower than that observed in the Spanish general population (Slimnai et al).  In other words, perhaps we cannot analyze the effects of alcohol consumption on cancer incidence in different countries without taking into account a precise evaluation of the dietary pattern, food and nutrients consumed by the participants.”

Evaluating the risk of developing cancer from alcohol in contrast to the effects of alcohol among subjects being treated for cancer: The authors state: “Light alcohol use among cancer survivors has been perceived as potentially beneficial for treatment-related adverse effects, although there is little evidence to support this concept,” but they do not reference studies showing such effects.  They also discuss the effects of alcohol on appetite, and quote one clinical trial lasting for 3-4 weeks that did not show a significant effect on appetite; that study reported: “Twenty-eight patients (48 %) in the wine arm reported an improvement in appetite at some point during the treatment period, whereas 22 patients (37 %) assigned to the nutritional supplement arm also reported improvement (p = 0.35).”  Their conclusions, even if correct, should not be based on one small study.

Ignoring the “net health effects” of moderate drinking on total mortality: Forum members were especially concerned that the authors failed to mention the most important net health effect of alcohol: the effect on total mortality.  In essentially all cohort studies, moderate drinkers live longer.  The authors state in the text that “larger studies and meta-analyses have failed to show an all-cause mortality benefit for low-volume alcohol use compared with abstinence, or intermittent use, which suggests the lack of a true benefit to daily alcohol use,” quoting only articles by Stockwell et al and by Goulden.  They carefully ignored the extensive reported evidence from most studies that shows the opposite (e.g., Klatsky & Udaltsova, and recently summarized by Xi et al and by de Gaetano & Costanzo).

De Gaetano also reflected on the disregard of the authors for discussing the net effects of alcohol on total morality: “Our group has had many publications on this topic, all of which showing the benefit on cardiovascular risk (Costanzo et al, 2010; Costanzo et al, 2011) and total mortality (Di Castelnuovo et al) associated with light-moderate alcohol consumption.  We have always mentioned that heavy and/or irregular alcohol consumption (binge drinking) is harmful, and have always tried to provide balanced information of the dose-relationship between alcohol and outcomes.  All of our studies support what has been described as a J-shaped curve for the association of alcohol with mortality (de Gaetano & Costanzo).”

Forum member Skovenborg commented: “Two years ago I wrote a book, ‘Wine and women – from useful knowledge to healthy enjoyment’. In the chapter discussing the association between alcohol consumption and cancer incidence and death I designed a figure based on the official Danish death statistics illustrating the risk of dying from cancer before the age of 75 years (24 women out of 200 women) and the risk of dying from an alcohol-related cancer before the age of 75 years (1 woman out of 200 women) to put the alcohol-cancer discussion into some perspective.”  He and other Forum members consider that the failure by the authors to mention total mortality was a serious omission in this publication.

What was the purpose of this publication?  While the data presented in the text of this paper relate to the effects of alcohol on the risk of developing cancer and the effects on patients being treated for cancer, the discussion is almost completely devoted to policy decisions to decrease drinking in the population (a topic unrelated to the data presented in the text).  Stated Forum member Stockley: “I was confused why a medically-orientated manuscript would include discussions of public health policy, which is both complex and cultural.”  The authors describe many ways of decreasing alcohol consumption in the population, but do not provide any data about whether or not the measures they propose may be successful.

Perhaps, most importantly, the authors do not discuss the potential weaknesses of the data on alcohol and disease that they quote (always a potential problem in observational studies), yet they end up thinking that they have the “correct final answer.” Then, they spend pages of discussion about policy: describing ways of decreasing alcohol consumption in the population, even though their paper does not provide any data upon which to base their assumptions.  The paper ends up as a tirade against any alcohol consumption.

Forum member Finkel, an oncologist, felt very strongly about this publication: “Frankly, I feel some sense of embarrassment as a member of the American Society of Clinical Oncology, probably since its founding or nearly so. This paper looks to me like a piece of political parroting, a polemic, not an objective scientifically based document. It again chews the cuds of tired old arguments that have been long since and repeatedly corrected. Some things just won’t stay dead! It deliberately ignores evidence and literature it doesn’t like, while selecting from the canon of the prohibitionist zealots among us, whose tirelessness might be admired were they intellectually honest.

“The mountain of epidemiological evidence and the hill of laboratory research supporting the J-shaped curve and the reduction of deaths among light and moderate drinkers threatens to bury this paper with the shame it deserves. While we have long known that the risks of a few cancers are increased by excessive drinking, the rest of the relationships still require clarification. What is clear, despite efforts to not see, are the net benefits of sensible drinking. Propaganda won’t help anyone.”

References from Forum review

Cao Y, Willett WC, Rimm EB, Stampfer MJ, Giovannucci EL. Light to moderate intake of alcohol, drinking patterns, and risk of cancer: results from two prospective US cohort studies.  BMJ 2015;351:h4238; doi: 10.1136/bmj.h4238.

Choi Y-J, Myung S-K, Lee J-H. Light Alcohol Drinking and Risk of Cancer: A Meta-analysis of Cohort Studies.  Cancer Research and Treatment 2017; doi: 10.4143/crt.2017.094. [Epub ahead of print].

Costanzo S, Di Castelnuovo A, Donati MB, Iacoviello L, de Gaetano G. Alcohol consumption and mortality in patients with cardiovascular disease: a meta-analysis.  J Am Coll Cardiol 2010;55:1339-1347.

Costanzo S, Di Castelnuovo A, Donati MB, Iacoviello L, de Gaetano G. Wine, beer or spirit drinking in relation to fatal and non-fatal cardiovascular events: a meta-analysis.  Eur J Epidemiol 2011;26:833-850.

de Gaetano G, Costanzo S. Alcohol and Health: Praise of the J Curves.  J Am Coll Cardiol 2017;70:923-925. doi: 10.1016/j.jacc.2017.07.710.

Di Castelnuovo A, Costanzo S, Bagnardi V, Donati MB, Iacoviello L, de Gaetano G. Alcohol dosing and total mortality in men and women: an updated meta-analysis of 34 prospective studies.  Arch Intern Med 2006;166:2437-2445.

Goulden R: Moderate alcohol consumption is not associated with reduced all-cause mortality. Am J Med 2016;129:180-186.

Katikireddi SV, Whitley E, Lewsey J, Gray L, Leyland AH. Socioeconomic status as an effect modifier of alcohol consumption and harm: analysis of linked cohort data.  Lancet Public Health 2017.  Online publication May 10, 2017.  http://dx.doi.org/10.1016/S2468-2667(17)30078-6

Klatsky AL, Udaltsova N. Alcohol drinking and total mortality risk.  Ann Epidemiol 2007;17:S63–S67.

Klatsky AL, Udaltsova N, Li Y, Baer D, Nicole Tran H, Friedman GD. Moderate alcohol intake and cancer: the role of underreporting.  Cancer Causes Control. 2014;25:693-699.

Larsson SC, Kaluza J, Wolk A. Combined impact of healthy lifestyle factors on lifespan: two prospective cohorts.   J Int Med 2017.  Pre-publication.  Doi: 10.1111.joim.12637.

Lee SJ, Sudore RL, Williams BA, Lindquist K, Chen HL, Covinsky KE. Functional limitations, socioeconomic status, and all-cause mortality in moderate alcohol drinkers.  J Am Geriatr Soc 2009;57:955–962.

Slimani N, Fahey M, Welch A,  Wirfält E, et al.  Diversity of dietary patterns observed in the European Prospective Investigation into Cancer and Nutrition (EPIC) project.  Public Health Nutrition 2002;5:1311-1328.

Stockwell T, Zhao J, Panwar S, et al: Do “moderate” drinkers have reduced mortality risk? A systematic review and meta-analysis of alcohol consumption and all-cause mortality. J Stud Alcohol Drugs 2016;77:185-198.

Xi B, Veeranki SP, Zhao M, Ma C, Yan Y, Mi J. Relationship of Alcohol Consumption to All-Cause, Cardiovascular, and Cancer-Related Mortality in U.S. Adults.  J Am Coll Cardiol 2017;70:913–922

Forum Summary

The present publication is an attempt by the American Society of Clinical Oncology to describe the relation between alcohol consumption and cancer, including the effects on the risk of developing cancer and effects among subjects currently being treated for cancer. It came to the conclusion that there is a need for the public to be warned about the use of alcohol because of its effects on cancer, and describes numerous approaches for decreasing alcohol use in the population.

Forum members considered this paper to markedly distort the associations between alcohol consumption, especially light drinking, and health outcomes. The authors were particularly remiss in not describing the net health effects of light to moderate consumption: longer longevity of life.  Their long discussion of policy implications, and ways of decreasing alcohol use in the population, were unrelated to the data they presented, and failed to describe how complex and culturally specific such recommendations are.  The authors describe many ways of decreasing alcohol consumption in the population, but do not provide any data about whether or not the measures they propose are successful.

While all Forum members agree that heavy alcohol consumption increases the risk of several cancers (information that oncologists should be aware of), light drinking has generally been associated only with a slight increase in breast cancer, but not with other types of cancer (especially when under-reporting of intake is considered). Further, factors such as dietary folate intake, patterns of drinking such as binge versus regular moderate drinking, and type of beverage generally consumed have been shown to modify even this relation.  Also, regular light or moderate drinking has been consistently shown to decrease the risk of cardiovascular disease (the leading cause of death), diabetes, dementia, and even total mortality, associations largely ignored in this paper.

Our Forum considers that this publication from the American Society of Clinical Oncology misses an opportunity to provide, for oncologists and for the public, up-to-date and balanced information of the true relations of alcohol consumption to the risk of cancer and other health outcomes. They have especially ignored the effects of moderate drinking on the risk of total mortality.

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Comments on this critique by the International Scientific Forum on Alcohol Research have been provided by the following members:

Giovanni de Gaetano, MD, PhD, Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo NEUROMED, Pozzilli, Italy

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

Ramon Estruch, MD, PhD, Hospital Clinic, IDIBAPS, Associate Professor of Medicine, University of Barcelona, Spain

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

Fulvio Mattivi, MSc, CAFE – Center Agriculture Food Environment, University of Trento, via E. Mach 1, San Michele all’Adige, Italy

Linda McEvoy, PhD, Department of Radiology, University of California at San Diego (UCSD), La Jolla, CA, USA

Erik Skovenborg, MD, specialized in family medicine, member of the Scandinavian Medical Alcohol Board, Aarhus, Denmark

Creina Stockley, PhD, MSc Clinical Pharmacology, MBA; 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

Pierre-Louis Teissedre, PhD, Faculty of Oenology–ISVV, University Victor Segalen Bordeaux 2, Bordeaux, France

David Van Velden, MD, Dept. of Pathology, Stellenbosch University, Stellenbosch, South Africa