Data sources: Searches for studies were made using MEDLINE, Current Contents, EMbase, CAB Abstracts and Core Biomedical Collection, and the reference lists of selected articles. A search was also made by hand of relevant journals.
Study selection: Studies were included if they met the following criteria: (i) case-control or cohort study published as an original article; (ii) findings expressed as odds ratio or relative risk (RR) considering at least three levels of alcohol consumption; (iii) papers reported the number of cases and controls and the estimates of the odds ratios or RR for each exposure level. When the results of a study were published more than once, only the most recent and complete article was included in the analysis.
Data extraction and synthesis: Two readers, blinded to the authors' names and affiliations and to the results pertaining to alcohol consumption, independently determined the eligibility and scored the quality of the studies. Pooled estimates of the effect of alcohol consumption on the risk of each investigated condition were based on a four-step procedure. Meta-regression models were fitted considering fixed and random-effect models and linear and nonlinear effects of alcohol intake.
Results: Of the 561 initially reviewed studies, 156 were selected for meta-analysis because of their quality. They included a total of 116 702 subjects. Strong trends in risk were observed for hypertension, liver cirrhosis, chronic pancreatitis, injuries, violence and for cancers of the oral cavity, oesophagus and larynx. Less strong relationships were observed with 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 ischaemic and haemorrhagic strokes. For coronary heart disease, a J-shaped relationship was observed with a minimum RR of 0.80 at 20 g ethanol/day, a significant protective effect up to 72 g/day, and a significant increased risk at 89 g/day. No clear relationship was observed for gastroduodenal ulcer.
Conclusions: This meta-analysis shows no evidence of a threshold effect for both neoplasms and several non-neoplastic diseases. A J-shaped distribution was observed only for coronary heart disease.