Critique 192: The association of alcohol consumption with the risk of prostate cancer –- 12 September 2016
Dickerman BA, Markt SC, Koskenvuo M, Pukkala E, Muccil LA, Kaprio J. Alcohol intake, drinking patterns, and prostate cancer risk and mortality: a 30-year prospective cohort study of Finnish twins. Cancer Causes Control 2016;27:1049–1058. DOI 10.1007/s10552-016-0778-6
Purpose Alcohol intake may be associated with cancer risk, but epidemiologic evidence for prostate cancer is inconsistent. We aimed to prospectively investigate the association between midlife alcohol intake and drinking patterns with future prostate cancer risk and mortality in a population-based cohort of Finnish twins.
Methods Data were drawn from the Older Finnish Twin Cohort and included 11,372 twins followed from 1981 to 2012. Alcohol consumption was assessed by questionnaires administered at two time points over follow-up. Over the study period, 601 incident cases of prostate cancer and 110 deaths from prostate cancer occurred. Cox regression was used to evaluate associations between weekly alcohol intake and binge drinking patterns with prostate cancer risk and prostate cancer-specific mortality. Within-pair co-twin analyses were performed to control for potential confounding by shared genetic and early environmental factors.
Results Compared to light drinkers (≤ 3 drinks/week; non-abstainers), heavy drinkers (> 14 drinks/week) were at a 1.46-fold higher risk (HR 1.46; 95 % CI 1.12, 1.91) of prostate cancer, adjusting for important confounders. Among current drinkers, binge drinkers were at a significantly increased risk of prostate cancer (HR 1.28; 95 % CI 1.06, 1.55) compared to non-binge drinkers. Abstainers were at a 1.90-fold higher risk (HR 1.90; 95 % CI 1.04, 3.47) of prostate cancer-specific mortality compared to light drinkers, but no other significant associations for mortality were found. Co-twin analyses suggested that alcohol consumption may be associated with prostate cancer risk independent of early environmental and genetic factors.
Conclusion Heavy regular alcohol consumption and binge drinking patterns may be associated with increased prostate cancer risk, while abstinence may be associated with increased risk of prostate cancer-specific mortality compared to light alcohol consumption.
Prostate cancer is a very common condition in ageing men, although it frequently is a stable type of cancer with low risk of metastasis. Previous research has been inconsistent on the relation of alcohol consumption to prostate cancer.
The present analyses are based on data from a study of more than 11,000 twins in Finland, whose alcohol consumption was assessed on two occasions; after the second alcohol assessment, subjects were followed for approximately 30 years during which their medical records were monitored for the development of prostate cancer or death from prostate cancer. Specifically, data were drawn from the Older Finnish Twin Cohort and included 11,372 twins followed from 1981 to 2012. By having twins in their study, the authors were able to evaluate alcohol intake among genetically similar subjects, removing genetic factors as a confounder for some subjects. The study was also able to evaluate binge drinking and cancer risk.
Specific comments on paper by Forum members: Members of the Forum thought that this was a straight-forward study with appropriate analyses. The authors admit that their dataset does not contain data on the type of beverage consumed, although it would be expected that it was mostly beer and spirits in this population.
Strengths of the study include the large sample size and the complete ascertainment of prostate cancer and confirmed pathology in this sample. The multivariable models adjusted for BMI, smoking, social class, education, and physical activity. The fully adjusted significant associations were an increase of prostate cancer incidence with heavy drinking and an increased risk for prostate cancer-specific mortality for abstainers (when compared with light drinkers). Most analyses combined never drinkers and former drinkers in the referent group; however, in supplementary analyses for this study, when using lifetime abstainers as the referent group, analyses still show a tendency for light drinkers to have a lower incidence of prostate cancer and a significantly lower risk of prostate cancer-specific mortality. In other words, lifetime abstainers tended to have higher cancer risk and higher prostate cancer-specific mortality than light drinkers.
The numbers of twins discordant for alcohol consumption were small; nevertheless, there was a lower risk of prostate cancer incidence (HR 0.34, 95% CI 0.15, 0.74) for the light-drinking twin when compared with the abstaining twin. For moderate drinkers and heavy drinkers, the incidence of prostate cancer was reduced for the drinking twin, but none of the effects were statistically significant. No effects of alcohol were seen between discordant twins for prostate cancer-specific mortality.
Forum member Finkel considered this to be a very good paper. “Despite the impressively large number of twins, however, the number of critically important discordant pairs does not reach a statistically powerful level. And, of course, while information on binge vs regular drinking is given, there’s no information regarding beverage choice. Nevertheless, a U-shaped relationship between quantity of consumption and prostate cancer is apparent, and we see that binges beget bumps.” Forum member Skovenborg commented: “I find the J-shaped relation between alcohol intake and prostate cancer mortality interesting; however, this is somewhat confusing and in sore need of a plausible biological model of explanation. Or is the J-curve in this case shaped by confounding factors?”
Reviewer Estruch commented: “The results of this study are really very interesting, since the relationship between alcohol and cancer continues to be a matter of concern. I would like to underline that the main conclusion is that light-alcohol consumption reduces the risk of prostate cancer-specific mortality compared to abstainers, and also compared to heavy regular alcohol consumption and binge drinking patterns. Unfortunately, no data on food intake have been included in the analysis as a confounding factor. In our experience (not yet published), the effect of alcohol intake (even moderately) on cancer varies depending on the dietary pattern of the consumers (healthy diets – i.e. Mediterranean diet vs. unhealthy diets – i.e. Western dietary pattern). The type of alcoholic beverages consumed is also important.”
Comments on wine and prostate cancer: While the present study did not differentiate effects according to type of alcoholic beverage consumed, Forum member Stockley carried out a review of the relation of wine to prostate cancer: “Six of eleven studies identified on the relationship between wine consumption and prostate cancer suggested there was no association between risk of prostate cancer and wine consumption. Two studies, however suggested that there was an inverse relationship for moderate wine, in particular red wine, consumption (Baglietto et al, Schoonen et al). One study suggested there was a positive relationship (Benedetti et al) and two studies suggested that there was a dose-dependent relationship with a threshold of 30-40 g alcohol/week of wine (Sutcliffe et al, Hayes et al). Thus, consistent with meta-analyses which provided no evidence of a material association between alcohol consumption and prostate cancer (Rota et al), the majority of the small number of observational studies available suggested there was no or an inverse relationship between moderate wine consumption and prostate cancer. The data was less certain, however, concerning an association with heavy wine consumption. On balance, these studies would thus tend to support a j-shaped relationship, as was seen for total alcohol intake in the present study.”
Reviewer Van Velden noted: “I agree with the comments thus far on this study. It is a pity that we cannot separate spirits from wine in this analysis, but the polyphenolic content of wine might have some protective effect on prostate cancer. The confirmation of the J-shaped curve for cancer and cardiovascular disease is interesting.”
Forum member de Gaetano commented: “This study seems to suggest that the natural history of prostate cancer (i.e., among abstainers) is favourably modified by moderate drinking in terms of both incidence and mortality; this could possibly be due to the non-alcoholic (polyphenol?) content of alcoholic beverages. Heavy drinking still protects against mortality but the excess alcohol counteracts the beneficial effects of polyphenols on cancer incidence. Thus, in respect to prostate cancer, drinking is better than non-drinking. The observed dissociation between incidence and mortality is difficult to explain, but might be related to factors affecting the development of metastases from the primary site and subsequent increased mortality (but not incidence) risk. Moderate or heavy drinking might similarly prevent cancer mortality by reducing metastases, while differently affecting cancer incidence. These are only speculations of course.”
References from Forum review
Baglietto L, Severi G, English DR, Hopper JL, Giles GG. Alcohol consumption and prostate cancer risk: results from the Melbourne collaborative cohort study. Int J Cancer 2006;119:1501-1504.
Benedetti A, Parent ME, Siemiatycki J. Lifetime consumption of alcoholic beverages and risk of 13 types of cancer in men: results from a case-control study in Montreal. Cancer Detect Prev 2009;32:352-362.
Hayes RB, Brown LM, Schoenberg JB, Greenberg RS, Silverman DT, Schwartz AG, Swanson GM, Benichou J, Liff JM, Hoover RN, Pottern LM. Alcohol use and prostate cancer risk in US blacks and whites. Am J Epidemiol 1996;143:692-697.
Rota M, Scotti L, Turati F, Tramacere I, Islami F, Bellocco R, Negri E, Corrao G, Boffetta P, La Vecchia C, Bagnardi V. Alcohol consumption and prostate cancer risk: a meta-analysis of the dose-risk relation. Eur J Cancer Prev 2012;21:350-359.
Schoonen WM, Salinas CA, Kiemeney LA, Stanford JL. Alcohol consumption and risk of prostate cancer in middle-aged men. Int J Cancer 2005;113:133-140.
Sutcliffe S, Giovannucci E, Leitzmann MF, Rimm EB, Stampfer MJ, Willett WC, Platz EA. A prospective cohort study of red wine consumption and risk of prostate cancer. Int J Cancer 2007;120:1529-1535.
Scientific data are mixed on the association of alcohol consumption with the risk of prostate cancer. In the present paper, the authors have used data from 11, 372 subjects in the Older Finnish Twin Cohort who provided data on alcohol intake on two occasions. They were followed for the development of prostate cancer from 1981 to 2012, during which 601 incident cases of prostate cancer and 110 deaths from prostate cancer occurred. The authors relate reported average alcohol intake, and whether or not the subject reported binge drinking, to the risk of prostate cancer and prostate cancer-specific death. They also evaluated the risks of prostate cancer among alcohol-discordant twins. The authors used current abstainers and ex-drinkers as the referent group in their main analyses, but did sensitivity analyses using never drinkers as an alternative referent group.
The type of beverage consumed was not known, so whether or not wine or beer consumption may have a different relation with prostate cancer than spirits intake cannot be determined. However, overall the data indicated a higher risk of prostate cancer from heavy intake and binge drinking, but also a high risk among abstainers. The number of discordant twins (for alcohol consumption) was too small for definitive results in terms of the risk of prostate cancer among subjects with the same or a similar genetic background , but the lowest risk was among light drinkers who did not binge drink. Even among this subset of the population, abstainers had higher risk than light drinkers.
Thus, the results of this well-done study suggest that there may be a J-shaped relation between alcohol consumption and prostate cancer risk. Light drinkers appear to have the most favorable results for both incident prostate cancer and prostate cancer-specific mortality. The risk for subjects reporting heavy drinking and binge drinking was higher for both incidence and mortality than the risk of light drinkers; for unexplained reasons, abstainers also tended to have higher risk of prostate cancer and mortality.
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Comments on this critique by the International Scientific Forum on Alcohol Research were 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 & Public Health, 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
Dominique Lanzmann-Petithory, MD, PhD, Nutrition Geriatrics, Hôpital Emile Roux, APHP Paris, Limeil-Brévannes, France
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
Erik Skovenborg, MD, specialized in family medicine, member of the Scandinavian Medical Alcohol Board, Aarhus, Denmark
David Van Velden, MD, Dept. of Pathology, Stellenbosch University, Stellenbosch, South Africa
Andrew L. Waterhouse, PhD, Department of Viticulture and Enology, University of California, Davis, USA