title: AURKA Phe31Ile polymorphism interacted with use of alcohol, betel quid, and cigarettes at multiplicative risk of oral cancer occurrence.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These findings reveal the functional Phe31Ile polymorphism tagSNP of AURKA may be a strong susceptibility gene in ABC-related oral cancer occurrence.
  
  
  CONCLUSIONS
  The results of this betel-related oral cancer study provide the evidence of environment-gene interaction for early prediction and molecular diagnosis.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chi-Pin
authors.initials: CP
authors.lastname: Lee
authors.affiliation: Environment-Omics-Diseases Research Center, China Medical University Hospital, Taichung, Taiwan.|Department of Health Risk Management, College of Management, China Medical University, Taichung, Taiwan.
authors.forename: Shang-Lun
authors.initials: SL
authors.lastname: Chiang
authors.affiliation: Department of Public Health, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Public Health, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yi-Shan
authors.initials: YS
authors.lastname: Tsai
authors.affiliation: Environment-Omics-Diseases Research Center, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chun-Hung
authors.initials: CH
authors.lastname: Hua
authors.affiliation: Department of Dentistry, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Yuan-Chien
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Eing-Mei
authors.initials: EM
authors.lastname: Tsai
authors.affiliation: Environment-Omics-Diseases Research Center, China Medical University Hospital, Taichung, Taiwan. ycko@mail.cmu.edu.tw.|Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, Taichung, Taiwan. ycko@mail.cmu.edu.tw.|, 2 Yude Road, Taichung, 40447, Taiwan. ycko@mail.cmu.edu.tw.
authors.forename: Ying-Chin
authors.initials: YC
authors.lastname: Ko
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects / Q000235:genetics*; D064096:Aurora Kinase A / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D031721:Piper betle; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000009:adverse effects / Q000235:genetics*
chemical_list: D009363:Neoplasm Proteins; C576917:AURKA protein, human; D064096:Aurora Kinase A
keywords: AURKA; CHAF1A; CHAF1B; Cancer susceptibility; Environment–gene interaction; Oral cancer; TagSNPs