Light Alcohol Drinking and Cancer

A Meta-Analysis

V. Bagnardi; M. Rota; E. Botteri; I. Tramacere; F. Islami; V. Fedirko; L. Scotti; M. Jenab; F. Turati; E. Pasquali; C. Pelucchi; R. Bellocco; E. Negri; G. Corrao; J. Rehm; P. Boffetta; C. La Vecchia

Disclosures

Ann Oncol. 2013;24(2):301-308. 

In This Article

Results

Figure 1 shows the detailed paper selection strategy for the meta-analysis. We identified a total of 13 814 non-unique papers (some papers were counted more than once if they reported on more than one cancer site of interest). We screened titles and abstracts for eligibility and excluded 13 128 non-unique papers because they were not strictly related to the alcohol–cancer association. The remaining 686 articles were considered of interest, and the full text was retrieved for detailed evaluation. We also reviewed their references and identified 84 additional papers of possible interest, making a total of 770 non-unique papers. Subsequently, 523 papers were excluded because they did not satisfy the inclusion criteria. A total of 247 non-unique papers reporting site-specific risk estimates were included in the meta-analysis. Sixteen papers reported estimates for two or more cancer sites and accounted for a total of 25 risk estimates. Accordingly, 222 unique papers were considered. The complete reference list by cancer site is reported in supplementary material S2, available at Annals of Oncology online.

Figure 1.

Flowchart of selection of studies for inclusion in meta-analysis.

Table 1 summarizes the main characteristics of the included studies by specific cancer site.

The analysis included ~60 000 cancer cases in the reference category of non-drinkers and 92 000 in the light drinkers' category. These numbers are slightly underestimated, since for 16 studies the number of exposed and/or non-exposed cases was not reported.

One hundred and ten out of 222 included studies (50%) investigated the association between light drinking and breast cancer, accounting for >75% of the total cases. Fifty-four studies (24%) reported estimates for at least one of the upper aerodigestive sites (23 estimates for oral cavity and pharynx, 27 for esophageal SCC and 13 for larynx), 54 studies (24%) for colorectal cancer (30 estimates for the colorectum, 19 for colon and rectum separately, 4 for colon only and 1 for rectum only). Twenty studies reported estimates for liver cancer.

Overall, case–control was the most common study design (68% of studies); 46% of the included studies were from North America, 29% from Europe, 18% from Asia and 6% from other regions or from more than one region; 22% of the studies did not present gender specific estimates; 46% of the reported estimates were adjusted for the main site-specific risk factors (for a list of considered site-specific risk factors, see supplementary material S3, available at Annals of Oncology online), while 15% of the estimates included occasional drinkers in the reference category.

Figure 2 shows the estimates for light drinkers versus non-drinkers reported in each single study, by site and year of publication. More than half the estimates (52%) derived from papers published since 2001. Heterogeneity between the study estimates was high (I 2 > 50%) for esophageal SCC, breast cancer and liver cancer, moderate or low for other sites.

Figure 2.

Study-specific relative risk (RR) estimates for low alcohol intake, by site and year of publication. Empty square: cohort study; full square: case–control study. I 2 proportion of total variation contributed by between-study variance. Gender-specific estimates from the same study were reported separately.

Figure 3 shows the site-specific pooled RRs. Low alcohol intake was found to significantly increase the risk of esophageal SCC (RR = 1.30; 95% CI 1.09–1.56), oral cavity and pharynx cancer (RR = 1.17; 95% CI 1.06–1.29) and female breast cancer (RR = 1.05; 95% CI 1.02–1.08). No significant association was observed between light drinking and cancer of the colorectum (RR = 0.99, 95% CI 0.95–1.04), liver (RR = 1.03, 95% CI 0.90–1.17) and larynx (RR = 0.90, 95% CI 0.73–1.10).

Figure 3.

Pooled relative risk (RR) estimates by cancer site.

Stratified analyses conducted according to study design, geographical area and gender, revealed similar estimates across strata (Table 2). Of note, the effect of low intake of alcohol on the risk of esophageal SCC was statistically significant only in studies carried out in Asian populations (RR = 1.49, 95% CI 1.12–1.98).

Little evidence for publication bias was detected for colorectal cancer (P = 0.059). The funnel plot showed that low alcohol consumption had a large positive effect in small studies (supplementary material S4, available at Annals of Oncology online). There was no evidence for publication bias for other cancer sites.

The effect of the quality of the reported estimates on the pooled RRs was evaluated in a sensitivity analysis that included only estimates adjusted for the main risk factors or estimates not considering occasional drinkers in the reference category of non-drinkers. As shown in supplementary material S5, available at Annals of Oncology online, the results did not change appreciably from those of the overall analysis.

Table 3 shows the attributable fraction and the worldwide number of deaths due to light alcohol drinking and to alcohol drinking in general, by site and sex, in 2004. We limited this analysis to oral cavity and pharynx, esophageal SCC and breast cancer.

Attributable fraction due to light drinking ranged from 0.95 for breast cancer in women to 4.87 for esophageal SCC in men. We estimated that 3521 male deaths and 1359 female deaths from oropharyngeal cancer were attributable to light drinking. The same figures were 16 116 and 7728 for esophageal SCC. We estimated that 4909 female deaths from breast cancer were attributable to light drinking.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....