Lee Chi-Pin, Chiang Shang-Lun, Lee Chien-Hung, Tsai Yi-Shan, Wang Zhi-Hong, Hua Chun-Hung, Chen Yuan-Chien, Tsai Eing-Mei, Ko Ying-Chin
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Environment-Omics-Diseases Research Center, China Medical University Hospital, Taichung, Taiwan.
Clin Oral Investig. 2015 Nov;19(8):1825-32. doi: 10.1007/s00784-015-1432-5. Epub 2015 Feb 21.
The expression levels of two DNA repair genes (CHAF1A and CHAF1B) and a chromosome segregation gene (AURKA) were susceptible to arecoline exposure, a major alkaloid of areca nut. We hypothesize that genetic variants of these genes might also be implicated in the risk of oral cancer and could be modified by substance use of betel quid or alcohol and cigarettes.
A case-control study, which included 507 patients with oral cancer and 717 matched controls, was performed in order to evaluate the cancer susceptibility by the tagging single-nucleotide polymorphisms (tagSNPs) in AURKA, CHAF1A, and CHAF1B using a genotyping assay and gene-environment interaction analysis.
The Phe31Ile polymorphism (rs2273535, T91A) of AURKA was significantly associated with an increased risk of oral cancer (odds ratio (OR) = 2.1, 95% confidence interval (CI) 1.2-3.5). The gene dosage of the 91A allele also showed a significant trend in risk of oral cancer (P = 0.008). Furthermore, we found the AURKA 91AA homozygote was modifiable by substance use of alcohol, betel quid, and cigarettes (ABC), leading to increased risk of oral cancer in an additive or a multiplicative model (combined effect indexes = 1.2-4.0 and 1.5-2.2, respectively). However, no association was observed between the genetic variants of CHAF1A or CHAF1B and oral cancer risk in the study.
These findings reveal the functional Phe31Ile polymorphism tagSNP of AURKA may be a strong susceptibility gene in ABC-related oral cancer occurrence.
The results of this betel-related oral cancer study provide the evidence of environment-gene interaction for early prediction and molecular diagnosis.
两种DNA修复基因（CHAF1A和CHAF1B）以及一种染色体分离基因（AURKA）的表达水平易受槟榔碱（槟榔的主要生物碱）暴露的影响。我们推测这些基因的遗传变异可能也与口腔癌风险有关，并且可能会受到槟榔、酒精和香烟使用情况的影响。
进行了一项病例对照研究，纳入507例口腔癌患者和717例匹配对照，通过基因分型检测和基因 - 环境相互作用分析，利用AURKA、CHAF1A和CHAF1B中的标签单核苷酸多态性（tagSNP）评估癌症易感性。
AURKA的Phe31Ile多态性（rs2273535，T91A）与口腔癌风险增加显著相关（优势比（OR）= 2.1，95%置信区间（CI）1.2 - 3.5）。91A等位基因的基因剂量在口腔癌风险中也显示出显著趋势（P = 0.008）。此外，我们发现AURKA 91AA纯合子会受到酒精、槟榔和香烟（ABC）使用情况的影响，在相加或相乘模型中导致口腔癌风险增加（联合效应指数分别为1.2 - 4.0和1.5 - 2.2）。然而，在该研究中未观察到CHAF1A或CHAF1B的遗传变异与口腔癌风险之间存在关联。
这些发现表明，AURKA具有功能的Phe31Ile多态性tagSNP可能是ABC相关口腔癌发生中的一个强易感基因。
这项与槟榔相关的口腔癌研究结果为早期预测和分子诊断提供了环境 - 基因相互作用的证据。
