Latino-Martel P, Arwidson P, Ancellin R, Druesne-Pecollo N, Hercberg S, Le Quellec-Nathan M, Le-Luong T, Maraninchi D.
Alcohol consumption and cancer risk: revisiting guidelines for sensible drinking. CMAJ 2011. DOI:10.1503. /cmaj.110363
A group of French scientists (from the Unit of Research on Nutritional Epidemiology, French National Institute for Agricultural Research, Bobigny, France; the French Institute for Prevention and Health Education, St. Denis, France; and the French National Cancer Institute) have published a paper in the Canadian Medical Association Journal (CMAJ) on guidelines for drinking and the relation of alcohol to cancer. They conclude that:
• Guidelines for sensible drinking are based on the short-term effects of consuming alcohol, such as social and psychological problems or admissions to hospital, and disregard the dose–response relationship between alcohol consumption and cancer risk.
• The current guidelines for sensible drinking for the general population are not adequate for the prevention of cancer.
• Revised guidelines that are based on complete and up-to-date scientific evidence are needed.
Background: The International Scientific Forum on Alcohol Research (ISFAR) was established in 2010 by a group of scientists and medical practitioners whose work/research relates to adverse and beneficial health effects of alcohol use and misuse, and their biologic mechanisms. The purpose of the Forum is to provide, on its open web-site www.bu.edu/alcohol-forum or alcoholforum4profs.org, timely critiques and comments by its members on emerging scientific publications and policy statements related to alcohol and health. Its overall goal is to assure that scientifically sound and balanced information on this topic is available to the public and to organizations and governmental agencies involved in setting alcohol policy. Forum members receive no compensation for their services.
Comments on the CMAJ alcohol and cancer report: Forum members considered that the current report contains many statements not consistent with current scientific research. If the paper was referred to as an “editorial” or “comments,” the authors would obviously be free to advise whatever drinking guidelines they wish. But this paper appears in a reputable journal, and the article is labeled “Analysis,” yet does not reflect current sound scientific data. The report is highly selective in finding a few publications that describe “methodological bias of most studies mentioning an apparent reduction of risk, such as nutritional, lifestyle or social confounders or the inclusion of people who used to consume alcohol, but no longer do, in the reference group.” The authors of this report ignore the considerable data from more scientifically sound research that have largely discredited such studies, as summarized recently by Fuller.1
The 1st key point of the paper is that “Guidelines for sensible drinking are based on the short-term effects of consuming alcohol, such as social and psychological problems or admissions to hospital, and disregard the dose–response relationship between alcohol consumption and cancer risk.” Currently, guidelines for drinking are based primarily on long-term health effects (including the risk of cancer) of drinking at varying levels.
It could be argued that the 2nd key point — “The current guidelines for sensible drinking for the general population are not adequate for the prevention of cancer” — has some merit, if one is discussing heavy drinking. With the exception of breast cancer (and possibly for colon cancer, an association refuted by many studies), an increase in cancer risk is associated almost exclusively with heavy drinking (especially alcoholism). This is the primary factor associated with upper aero-digestive cancers, liver cancer, and other “alcohol-related cancers.” These are not common outcomes associated with moderate drinking. More importantly, the authors ignore the consistent data from developed countries around the world showing that moderate drinkers are at lower risk of all-cause mortality than are abstainers. Even taking into account an increase in risk for certain types of cancer from alcohol consumption, the authors do not acknowledge that total mortality is higher among abstainers (including lifetime abstainers) than among moderate drinkers.
The 3rd key point of this paper, “Revised guidelines that are based on complete and up-to-date scientific evidence are needed,” might also be considered reasonable. However, throughout the paper are presented statements that are not based on sound, balanced, scientific research.
Specific concerns regarding the report: Forum members were unanimous in criticizing the report for using selected (and often erroneous) scientific data supporting their conclusions. For example, the Forum thought that the authors failed to present a balanced scientific overview on the following:
1. Lower total mortality among moderate drinkers: The support of the message that “less is better,” still promoted by WHO Europe, flies in the face of meta-analysis data of lower mortality for moderate drinkers than for abstainers. For example, in a comprehensive meta-analysis, Di Castelnuovo et al2 found that consumption of alcohol, up to 4 drinks per day in men and 2 drinks per day in women, was associated with a lower risk of total mortality of 18% in women and 17% in men. This finding has been strengthened by the recent analysis by Fuller1 of the association between alcohol and total mortality among more than 100,000 Americans. Much of this protection from moderate drinking relates to decreased risk of death from cardiovascular disease, as consistently shown in meta-analyses.3-5
Many diseases such as cancer affect older people much more than younger. The cardiovascular and other possible benefits of alcohol are most likely to be visible in older age groups, a time when much research suggests alcohol’s positive effects outweigh its negative effects.6,7 As one Forum reviewer states, “If older people are encouraged to drink no alcohol, then morbidity and mortality may increase rather than decrease among moderate drinkers; both Connor et al6 and Rehm et al,7 for example, calculated a net positive effect for using alcohol in older age groups.”
2. Threshold effects: The paper quotes the 2007 review from World Cancer Research Fund/American Institute for Cancer Research8 for the conclusion: “No threshold for risk-free consumption was identified.” However, thresholds were identified in that document (and in many others), such as an increased risk of colorectal cancer is only apparent above a threshold of 30 g/day of ethanol for both sexes, and cirrhosis (associated with heavy drinking) is an essential precursor of liver cancer caused by alcohol.8
3. Importance of smoking and diet on the association of alcohol with cancer: The paper fails to point out the importance of associated smoking in the risk of upper aero-digestive cancers; in the absence of tobacco smoking there seems to be little or no effect of moderate alcohol consumption on the risk of such cancers. For example, in the Million Women Study,9 increasing alcohol intake was strongly associated with an increased risk of cancers of the upper aerodigestive tract among current smokers, but was not associated with an increased risk in never smokers or past smokers.9
A Forum reviewer who carries out research in the field pointed out that the risk of cancer associated with alcohol seems to be more important for smokers, young people, addicts, and women. However, numerous studies have shown, for example, that moderate wine consumption during meals as part of a Mediterranean-type diet is associated with many measures of better health.10-12 The reviewer adds: “It is easy to reach erroneous conclusions when a particular food factor is analyzed separately from cultural and culinary habits and when the net health effects are not taken into consideration.”
4. Dietary and genetic modification of effects of alcohol: The analysis mentions interference with the metabolism of folates as a mechanism leading to alcohol-related cancer. The authors of the present report do not include in their references that to the first prospective study based on a European population, which showed that a previously established association between alcohol intake and risk of breast cancer was present mainly among women with low folate intake, and there was no association among women with a folate intake higher than 350 μg per day.13 While the effects of genes on the alcohol-cancer association are still poorly understood, a number of recent studies,14,15 but not all,16 have shown genetic modification of the effects of alcohol on cancer risk. Undoubtedly, future research will help identify phenotypes that increase or decrease the susceptibility to cancer associated with alcohol consumption.
Reasons why people consume alcohol: The authors of the report seem to believe that including categories for sensible or low-risk drinking in guidelines leads people to start drinking alcohol. Humans have consumed various types of alcoholic beverages since long before recorded history. The reasons why some people consume such beverages and others do not are strongly related to cultural norms. It is unlikely that a particular set of guidelines for a country plays a major role in the initiation of consumption, although it may be of some help in reducing consumption in individuals who drink excessively.
Differences among countries in drinking guidelines: As illustrated by the authors of the CMAJ report, a comparison of worldwide recommendations on alcohol consumption reveals wide disparity among countries. Reasons for such discrepancies were described well by Harding and Stockley,17 who stated that such differences “could imply that many of the recommendations do not adequately accommodate the science, given that the science is equally valid worldwide. Such a view, however, would be an oversimplification of the problem that those who formulate such guidelines face. The objective of guidelines is to influence and change behavior among target populations. It follows, therefore, that several factors then become relevant: behavior that is thought to be in need of change, the culture and mindset of the target populations, and the kind of message that is likely to be effective.”17 These authors add that there is another step after tentative guidelines are developed by groups that include scientists: “Finally, in many countries, any government guidelines may have to be approved or endorsed by government ministers before they can be implemented. This step adds a further source of variability as, inevitably, political judgment is involved. In light of these factors, therefore, it is likely, if not inevitable, that governments produce recommendations that differ markedly from one another.”17
Does the reporting of potentially beneficial health effects of moderate drinking increase abuse? A question often raised is whether presenting accurate information on the potentially beneficial health effects of moderate drinking, or including “sensible drinking” in guidelines, increases abuse. There are little data on this topic. It is interesting that in Chile between 1997 and 2003, Leighton and his colleagues18 carried out a public program providing information on moderate drinking to the public. Based on surveys of drinking patterns and attitudes before and after the program was implemented, they found no increase in alcohol consumption in Chile. Rather, their surveys showed that people were drinking less on any given occasion, but doing so more frequently and with food. 18
Forum reviewers were not aware of guidelines that suggest that non-drinkers should begin to drink. Further, guidelines state clearly that any sensible drinking limits do not apply to children, pregnant women, etc. The consensus of Forum members is that decisions regarding drinking habits should be done by individuals in consultation with their physicians. One of the most respected senior physician/scientists in the field, Dr. Arthur Klatsky of California, has provided some key recommendations regarding giving advice on alcohol use to individual patients: “Such advice depends on the individual’s age, sex, past alcohol use experience, cardiovascular risk, and other factors.” Klatsky added, “While some patients may rationalize their heavy drinking because of its purported health effects, I have yet to find someone who had developed alcohol abuse because of messages about the health effects of moderate drinking.”19
References from Forum Review:
1. Fuller TD. Moderate alcohol consumption and the risk of mortality. Demography 2011. DOI 10.1007/s13524-011-0035-2.
2. 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.
3. Maclure M. Demonstration of deductive meta-analysis: ethanol intake and risk of myocardial infarction. Epidemiol Review 1993;15:328-351.
4. Corrao G, Rubbiati L, Bagnardi V, Zambon A, Poikolainen K. Alcohol and coronary heart disease: a meta-analysis. Addiction. 2000;95:1505-1523.
5. Ronksley PE, Brien SE, Turner BJ, Mukamal KJ, Ghali WA. Association of alcohol consumption with selected cardiovascular disease outcomes: a systematic review and meta-analysis. BMJ 2011;342:d671; doi:10.1136/bmj.d671.
6. Connor J, Broad J, Rehm J, Vander Hoorn S, Jackson R. The burden of death, disease, and disability due to alcohol in New Zealand. N Z Med J 2005;118(1213):U1412.
7. Rehm J, Patra J, Taylor B. Harm, benefits, and net effects on mortality of moderate drinking of alcohol among adults in Canada in 2000. Ann Epidemiol 2007;17(Suppl):S81-S86.
8. Alcoholic drinks. In: Food, nutrition physical activity and the prevention of cancer: a global perspective. Washington (DC): World Cancer Research Fund/American Institute for Cancer Research, 2007. p 157-171.
9. Allen NE, Beral V, Casabonne D, Kan SW, Reeves GK, Brown A, Green J ; on behalf of the Million Women Study Collaborators. Moderate alcohol intake and cancer incidence in women. J Natl Cancer Inst 2009;101:296–305.
10. Babio N, Bulló M, Basora J, Martínez-González MA, Fernández-Ballart J, Márquez-Sandoval F, Molina C, Salas-Salvadó J; Nureta-PREDIMED Investigators. Adherence to the Mediterranean diet and risk of metabolic syndrome and its components. Nutr Metab Cardiovasc Dis 2009;19:563-570. Epub 2009 Jan 26.
11. Tangney CC, Kwasny MJ, Li H, Wilson RS, Evans DA, Morris MC. Adherence to a Mediterranean-type dietary pattern and cognitive decline in a community population. Am J Clin Nutr 2011;93601-607. Epub 2010 Dec 22.
12. Urquiaga I, Strobel P, Perez D, et al. Mediterranean diet and red wine protect against oxidative damage in young volunteers. Atherosclerosis 2010;211:694-699. Epub 2010 Apr 21.
13. Tjønneland A et al. Folate intake, alcohol and the risk of breast cancer among post-menopausal women in Denmark. Eur J Clin Nutr 2006;60:280-286.
14. Benzon Larsen S, Vogel U, Christensen J, Hansen RD, Wallin H, Overvad K, Tjønneland A, Tolstrup J. Interaction between ADH1C Arg(272)Gln and alcohol intake in relation to breast cancer risk suggests that ethanol is the causal factor in alcohol related breast cancer. Cancer Lett 2010 Sep 28;295(2):191-7. Epub 2010 Mar 28.
15. De Feo E, Rowell J, Cadoni G. et al. A case-control study on the effect of apoliprotein E genotype on head and neck cancer risk. Cancer Epidemiol Biomarkers Prev 2010;19:2839-2846.
16. KawaseT, Matsuo K, Hiraki A, et al. Interaction of the effects of alcohol drinking and polymorphisms in alcohol-metabolizing enzymes on the risk of female breast cancer in Japan. J Epidemiol 2009;19:244-250.
17. Harding R, Stockley CS. Communicating through government agencies. Ann Epidemiol 2007;17:S98–S102.
18. Leighton F. Panel Discussion V: The message on moderate drinking. Ann Epidemiol 2007;17:S110–S111.
19. Klatsky A. Giving advice to individuals. Panel Discussion V: The message on moderate drinking. Ann Epidemiol 2007;17:S110–S111.
The Canadian Medical Association Journal has published a commentary by some French scientists relating drinking guidelines to the association between alcohol and cancer. They conclude that the current guidelines for sensible drinking for the general population are not adequate for the prevention of cancer, and revisions and eventual exclusion of such guidelines are needed.
Forum reviewers agree that alcohol consumption, especially heavy intake, increases the risk of certain types of cancer. However, they consider that the opinions of the authors in the paper (labeled as an “Analysis” rather than an editorial or comments) do not reflect current sound scientific data, that the report is highly selective in citing a small number of papers that support their opinions, and that the authors have ignored a huge amount of recent data from more scientifically sound research that have largely discredited such studies. Further, the report provides no mention of the consistent finding from studies around the world that moderate drinkers tend to have lower all-cause mortality risk than do abstainers.
Scientific data over many decades have shown that excessive or irresponsible alcohol use has severe adverse health effects, including an increase in the risk of certain cancers. On the other hand, moderate drinking is associated with lower risk of cardiovascular disease and many other diseases of ageing and with all-cause mortality. A very large number of experimental studies, including results from human trials, have described biological mechanisms for the protective effects of alcoholic beverages against such diseases. A number of comprehensive meta-analyses provide much more accurate, up to date, and scientifically balanced views than does the current paper; such documents may be better sources of data upon which guidelines to the public regarding alcohol consumption should be based.
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Comments by the International Scientific Forum on Alcohol Research on this paper have been provided by the following members:
Maria Isabel Covas, DPharm, PhD, Cardiovascular Risk and Nutrition Research Group, Institut Municipal d´Investigació Mèdica, Barcelona, Spain.
Giovanni de Gaetano, MD, PhD, Research Laboratories, Catholic University, Campobasso, Italy.
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.
Ulrich Keil, MD, PhD, Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.
Federico Leighton, MD, Laboratorio de Nutricion Molecular, Facultad de Ciencias Biologicas, Universidad Catolica de Chile, Santiago, Chile.
Ross McCormick PhD, MSC, MBChB, Associate Dean, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.
Francesco Orlandi, MD, Dept. of Gastroenterology, Università degli Studi di Ancona. Italy.
Erik Skovenborg, MD, Scandinavian Medical Alcohol Board, Practitioner, Aarhus, Denmark.
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.
Pierre-Louis Teissedre, PhD, Faculty of Oenology – ISVV, University Victor Segalen Bordeaux 2, Bordeaux, France.
Gordon Troup, MSc, DSc, School of Physics, Monash University, Victoria, Australia.
Fulvio Ursini, MD, Dept. of Biological Chemistry, University of Padova, Padova, Italy.
David Van Velden, MD, Dept. of Pathology, Stellenbosch University, Stellenbosch, South Africa.
David Vauzour, PhD, Senior Research Associate, Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, UK.
Andrew L. Waterhouse, PhD, Marvin Sands Professor, Department of Viticulture and Enology, University of California, Davis. USA.