Department of Epidemiology, University of North Carolina at Chapel Hill, 100 Market Street, Chapel Hill, NC 27516, USA.
Cancer Epidemiol Biomarkers Prev. 2011 Nov;20(11):2438-49. doi: 10.1158/1055-9965.EPI-11-0649. Epub 2011 Sep 22.
Single-nucleotide polymorphisms (SNP) in alcohol metabolism genes are associated with squamous cell carcinoma of the head and neck (SCCHN) and may influence cancer risk in conjunction with alcohol. Genetic variation in the oxidative stress pathway may impact the carcinogenic effect of reactive oxygen species produced by ethanol metabolism. We hypothesized that alcohol interacts with these pathways to affect SCCHN incidence.
Interview and genotyping data for 64 SNPs were obtained from 2,552 European- and African-American subjects (1,227 cases and 1,325 controls) from the Carolina Head and Neck Cancer Epidemiology Study, a population-based case-control study of SCCHN conducted in North Carolina from 2002 to 2006. We estimated ORs and 95% confidence intervals (CI) for SNPs and haplotypes, adjusting for age, sex, race, and duration of cigarette smoking. P values were adjusted for multiple testing using Bonferroni correction.
Two SNPs were associated with SCCHN risk: ADH1B rs1229984 A allele (OR = 0.7; 95% CI, 0.6-0.9) and ALDH2 rs2238151 C allele (OR = 1.2; 95% CI, 1.1-1.4). Three were associated with subsite tumors: ADH1B rs17028834 C allele (larynx, OR = 1.5; 95% CI, 1.1-2.0), SOD2 rs4342445 A allele (oral cavity, OR = 1.3; 95% CI, 1.1-1.6), and SOD2 rs5746134 T allele (hypopharynx, OR = 2.1; 95% CI, 1.2-3.7). Four SNPs in alcohol metabolism genes interacted additively with alcohol consumption: ALDH2 rs2238151, ADH1B rs1159918, ADH7 rs1154460, and CYP2E1 rs2249695. No alcohol interactions were found for oxidative stress SNPs.
Previously unreported associations of SNPs in ALDH2, CYP2E1, GPX2, SOD1, and SOD2 with SCCHN and subsite tumors provide evidence that alterations in alcohol and oxidative stress pathways influence SCCHN carcinogenesis and warrant further investigation.
酒精代谢基因中的单核苷酸多态性（SNP）与头颈部鳞状细胞癌（SCCHN）有关，并且可能与酒精一起影响癌症风险。氧化应激途径中的遗传变异可能会影响乙醇代谢产生的活性氧的致癌作用。我们假设酒精与这些途径相互作用，从而影响 SCCHN 的发病率。
从 2002 年至 2006 年在北卡罗来纳州进行的一项针对 SCCHN 的基于人群的病例对照研究——卡罗来纳头颈部癌症流行病学研究中，对 2552 名欧洲裔和非裔美国受试者（1227 例病例和 1325 例对照）的 64 个 SNP 的访谈和基因分型数据进行了分析。我们通过 Bonferroni 校正调整多重检验，调整了年龄、性别、种族和吸烟持续时间，估计了 SNP 和单倍型的 ORs 和 95%置信区间（CI）。
有两个 SNP 与 SCCHN 风险相关：ADH1B rs1229984 A 等位基因（OR=0.7；95%CI，0.6-0.9）和 ALDH2 rs2238151 C 等位基因（OR=1.2；95%CI，1.1-1.4）。有三个 SNP 与肿瘤部位相关：ADH1B rs17028834 C 等位基因（喉，OR=1.5；95%CI，1.1-2.0）、SOD2 rs4342445 A 等位基因（口腔，OR=1.3；95%CI，1.1-1.6）和 SOD2 rs5746134 T 等位基因（下咽，OR=2.1；95%CI，1.2-3.7）。在酒精代谢基因中，有四个 SNP 与酒精摄入呈加性相互作用：ALDH2 rs2238151、ADH1B rs1159918、ADH7 rs1154460 和 CYP2E1 rs2249695。未发现氧化应激 SNP 与酒精的相互作用。
ALDH2、CYP2E1、GPX2、SOD1 和 SOD2 中以前未报道的 SNP 与 SCCHN 和肿瘤部位的相关性提供了证据，表明酒精和氧化应激途径的改变会影响 SCCHN 的癌变，并值得进一步研究。
