Quantification of the association between alcohol drinking and risk of esophageal squamous cell carcinoma (ESCC) is an open issue, particularly among light alcohol drinkers, never-smokers, and Asian populations, in which some high-risk polymorphisms in alcohol metabolizing genes are more prevalent. To address these issues, we conducted a systematic review and meta-analysis using 40 case-control and 13 cohort studies that reported on the risk associated with alcohol drinking for at least three levels of consumption. In studies adjusted for age, sex, and tobacco smoking, the relative risk (RR) and 95% confidence interval (CI) for the association between light alcohol drinking (≤ 12.5 g/d) and risk of ESCC was 1.38 (1.14-1.67). The association was slightly stronger in Asian countries than in other populations. The adjusted RRs (95% CIs) were 2.62 (2.07-3.31) for moderate drinking (>12.5-<50 g/d) and 5.54 (3.92-7.28) for high alcohol intake (≥50 g/d); the RRs were slightly higher in non-Asian populations. In prospective studies, the RR (95% CI) was 1.35 (0.92-1.98) for light, 2.15 (1.55-2.98) for moderate, and 3.35 (2.06-5.46) for high alcohol intakes; light drinking showed an association with ESCC in Asia (five studies) but not in other regions (three studies). Among never-smokers (nine studies), the RR (95% CI) was 0.74 (0.47-1.16) for light, 1.54 (1.09-2.17) for moderate, and 3.09 (1.75-5.46) for high intakes. This meta-analysis further corroborates the association of moderate and high alcohol intake with risk of ESCC and provides risk estimates based on multiple prospective studies. Light alcohol intake appears to be associated to ESCC mainly in studies in Asia, which suggests a possible role of genetic susceptibility factors.
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