A Case-Control Study on the Effect of Apoliprotein E Genotype on Head and Neck Cancer Risk

Background: The apolipoprotein E gene (apoE) has three major isoforms encoded by the epsilon 2, epsilon 3, and epsilon 4 alleles, with the epsilon 4 allele associated with hypercholesterolemia and the epsilon 2 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 epsilon 2 allele. Females carrying at least one epsilon 2 allele showed a 60% risk reduction (OR, 0.43; 95% CI, 0.21-0.90) for HNC compared with epsilon 3 homozygotes. A statistically significant interaction was found between alcohol use and the epsilon 4 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 epsilon 4 allele, with respect to epsilon 3 homozygote nondrinkers. Conclusions: Our study provides novel evidence of a possible protective effect of the epsilon 2 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. Cancer Epidemiol Biomarkers Prev; 19(11); 2839-46. (C) 2010 AACR.