Elsevier

Preventive Medicine

Volume 38, Issue 5, May 2004, Pages 613-619
Preventive Medicine

A meta-analysis of alcohol consumption and the risk of 15 diseases

https://doi.org/10.1016/j.ypmed.2003.11.027Get rights and content

Abstract

Background. To compare the strength of evidence provided by the epidemiological literature on the association between alcohol consumption and the risk of 14 major alcohol-related neoplasms and non-neoplastic diseases, plus injuries.

Methods. A search of the epidemiological literature from 1966 to 1998 was performed by several bibliographic databases. Meta-regression models were fitted considering fixed and random effect models and linear and nonlinear effects of alcohol intake. The effects of some characteristics of the studies, including an index of their quality, were considered.

Results. Of the 561 initially reviewed studies, 156 were selected for meta-analysis because of their a priori defined higher quality, including a total of 116,702 subjects. Strong trends in risk were observed for cancers of the oral cavity, esophagus and larynx, hypertension, liver cirrhosis, chronic pancreatitis, and injuries and violence. Less strong direct relations were observed for cancers of the colon, rectum, liver, and breast. For all these conditions, significant increased risks were also found for ethanol intake of 25 g per day. Threshold values were observed for ischemic and hemorrhagic strokes. For coronary heart disease, a J-shaped relation was observed with a minimum relative risk of 0.80 at 20 g/day, a significant protective effect up to 72 g/day, and a significant increased risk at 89 g/day. No clear relation was observed for gastroduodenal ulcer.

Conclusions. This meta-analysis shows no evidence of a threshold effect for both neoplasms and several non-neoplastic diseases. J-shaped relations were observed only for coronary heart disease.

Introduction

Alcohol drinking is a major correlate of health and disease, and it has been associated to cancer, cardiovascular diseases, digestive tract conditions, accidents, and violence.

Although alcohol is not known to be carcinogenic in animal experimentation, there is strong epidemiological evidence that consumption of alcoholic beverages increases the risk of cancers of the oral cavity and pharynx, esophagus, and larynx [1], [2]. The risks are essentially thought to be related to ethanol content and appear to be linked to the most commonly used alcoholic beverages in each population. These risks tend to increase with the amount of ethanol drunk, but it is still unclear whether there is any defined threshold below which no effect is evident [1], [2]. Alcohol drinking is also associated with primary liver cancer, although this relation is difficult to investigate in epidemiological studies because most alcohol-related liver cancers follow a cirrhotic degeneration, which leads to a reduction of alcohol drinking [3].

Alcohol drinking has also been linked to cancers of the large bowel in both sexes [2] and breast cancer in women [4]. Although these associations are still open to discussion, these are the two major causes of cancer death in developed countries after lung cancer [5], [6], and therefore even a moderate excess risk may have important public health implications. Furthermore, alcohol drinking is strongly related to mortality from liver cirrhosis, chronic pancreatitis, hypertension, stroke, accidents, and violence [7], [8].

It has been suggested, in contrast, that moderate alcohol consumption (i.e., <25 g/day) protects against coronary heart disease [9]. A number of plausible mechanisms have been formulated, including the relation between alcohol drinking and cholesterol, high density lipoprotein, apolipoproteins, fibrinolysis, coagulation factors, and blood pressure, but none has as yet been firmly established [10].

It has also been suggested that the protection is specific, or greater, for selected types of alcoholic beverages, such as red wine (due to phenolic compounds, flavonoids or tannin) [11], [12]. Independently of the population studied, and hence of the most frequent type of alcohol beverages, however, most studies found reduced risk of cardiovascular diseases in moderate drinkers compared with nondrinkers [8], [9], [13], [14], [15], [16].

Several comprehensive reviews are available on the effect of alcohol on disease [1], [17], [18], [19], [20], [21], [22], [23]. To evaluate the global effect of alcohol on a population level, a more accurate quantification of its effects and of its dose–risk relation on various diseases is nonetheless required. This paper thus also includes an original analysis of risks for moderate doses, which are of specific interest for medical practice.

Section snippets

Methods

The following 15 conditions considered to be alcohol-related were included in the meta-analysis: malignant neoplasms of the oral cavity and pharynx, of the esophagus, of the colon, of the rectum, of the liver, of the larynx, and of the breast, essential hypertension, coronary heart disease, hemorrhagic stroke, ischemic stroke, gastroduodenal ulcer, liver cirrhosis, chronic pancreatitis, and injuries and violence. The methods of this work are described in details elsewhere [18], [19].

Articles

Results

A total of 561 studies were retrieved. Of these, 240 were included in the analysis (because they gave information on number of subjects, on RRs for more than two levels of alcohol consumption, and were not included in subsequent reports), and 156 were selected for final analysis because of their higher quality, and the results refer therefore to 156 studies. Of the selected studies, 148 reported adjusted estimates for the main risk covariates of interest, 99 were case-control, and 57 cohort

Discussion

This work has some of the limitations, but also most strengths, of meta-analyses of published studies. Thus, bias towards selective publications of studies showing inverse relations with moderate levels of alcohol drinking was apparent for coronary heart disease and is likely to have occurred—in various directions—for other diseases, including esophageal and laryngeal cancer, too. The overall pooled estimates may be systematically influenced by the study characteristics. We used three

Acknowledgements

Supports for this study came from the Italian Ministry of Health, the Italian Ministry of the University and Scientific and Technologic Research, COFIN 2003, and the Italian Association for Research on Cancer.

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