Institute of Hygiene, Università Cattolica del Sacro Cuore, Rome, Italy.
Cancer Epidemiol Biomarkers Prev. 2010 Nov;19(11):2839-46. doi: 10.1158/1055-9965.EPI-10-0624. Epub 2010 Sep 22.
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.
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.
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.
Our study provides novel evidence of a possible protective effect of the ε2 allele against HNC, probably due to its increased antioxidant properties.
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.
载脂蛋白 E 基因（apoE）有三个主要的等位基因，分别是 ε2、ε3 和 ε4，其中 ε4 等位基因与高胆固醇血症有关，而 ε2 等位基因则相反。此前已有报道称，胆固醇水平与头颈部癌症（HNC）呈负相关，尽管迄今为止尚未探讨 apoE 基因型与 HNC 之间的关系。
对 417 例 HNC 病例和 436 例医院对照进行 apoE 多态性基因分型。采用逻辑回归调整后的比值比（OR）和 95%置信区间（CI）来探讨 HNC 与潜在危险因素之间的关系。并进行了基因-环境交互作用分析。
携带至少一个 ε2 等位基因的个体 HNC 风险降低 40%（OR，0.58；95%CI，0.31-1.05），具有边缘统计学意义。与 ε3 纯合子相比，携带至少一个 ε2 等位基因的女性 HNC 风险降低 60%（OR，0.43；95%CI，0.21-0.90）。发现酒精使用与 ε4 等位基因之间存在统计学显著的交互作用（交互作用 P 值=0.04），与 ε3 纯合子非饮酒者相比，携带 ε4 等位基因的既往饮酒者的风险增加了 2 倍（OR，2.06；95%CI，0.95-4.48）。
本研究提供了 apoE 等位基因 ε2 可能对 HNC 具有保护作用的新证据，这可能是由于其增加的抗氧化特性。
根据我们的研究结果，apoE 可能在癌症发生中发挥与调节血清胆固醇水平不同的作用。
