Background: The apolipoprotein E gene (apoE) has three major isoforms encoded by the ε2, ε3, and ε4 alleles, with the ε4 allele associated with hypercholesterolemia and the ε2 allele with the opposite effect. An inverse relationship between cholesterolemia and head and neck cancer (HNC) has been previously reported, although the relationship between apoE genotypes and HNC has not been explored to date. Methods: Four hundred and seventeen HNC cases and 436 hospital controls were genotyped for apoE polymorphisms. Adjusted odds ratios (ORs) and 95% confidence intervals (CI) from logistic regression were used to explore the relationship between HNC and putative risk factors. A gene-environment interaction analysis was done. Results: A borderline significant 40% decreased HNC risk (OR, 0.58; 95% CI, 0.31-1.05) was observed for individuals carrying at least one ε2 allele. Females carrying at least one ε2 allele showed a 60% risk reduction (OR, 0.43; 95% CI, 0.21-0.90) for HNC compared with ε3 homozygotes. A statistically significant interaction was found between alcohol use and the ε4 allele (P for interaction = 0.04), with a 2-fold increased risk (OR, 2.06; 95% CI, 0.95-4.48) among ever drinkers with an ε4 allele, with respect to ε3 homozygote nondrinkers. Conclusions: Our study provides novel evidence of a possible protective effect of the ε2 allele against HNC, probably due to its increased antioxidant properties. Impact: According to our results, apolipoprotein E may play a different role in carcinogenesis other than its well-known role in regulating blood serum cholesterol levels.
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