title: NAT2 fast acetylator genotypes are associated with an increased risk for lung cancer with wildtype epidermal growth factor receptors in Taiwan.
abstract: Identifying the risk factors responsible for lung cancer especially for nonsmokers is critical for both its prevention and treatment. Studies have linked the polymorphisms in N-acetyltransferases (NAT2), a key enzyme for metabolism of hydrocarbons, with lung cancer in Asian female nonsmokers. Since a high percentage of lung adenocarcinoma in Asian female nonsmokers contains activating hotspot mutations in epidermal growth factor receptors (EGFR), we hypothesized that NAT2 polymorphisms might represent a risk factor in lung cancer with EGFR mutations. We studied NAT polymorphisms in 117 nonsmall cell lung cancer (NSCLC) patients and in 119 healthy controls and EGFR hotspot mutations in exons 18-21 in 100 of the 117 patients using polymerase chain reactions. NAT2 fast acetylator genotypes were significantly associated with patients with lung cancer (P = 0.04, odds ratio (OR): 1.90, 95% confidence interval (CI): 1.02-3.57). Further analyses revealed that NAT2 fast acetylator genotypes were significantly associated with NSCLC with wildtype EGFR (P = 0.008, OR: 3.16, 95% CI: 1.31-7.63), but not with those with EGFR mutations (P = 0.40). Therefore, NAT2 fast acetylator genotypes are a potential risk factor especially for lung cancer with wildtype EGFR.
authors.affiliation: Department of Medicine, School of Medicine, Taipei Medical University, Taiwan.
authors.forename: Chun-Nin
authors.initials: CN
authors.lastname: Lee
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Yu
authors.forename: Kuan-Jen
authors.initials: KJ
authors.lastname: Bai
authors.forename: Jer-Hua
authors.initials: JH
authors.lastname: Chang
authors.forename: Chia-Lang
authors.initials: CL
authors.lastname: Fang
authors.forename: Han-Lin
authors.initials: HL
authors.lastname: Hsu
authors.forename: Biing-Shiung
authors.initials: BS
authors.lastname: Huang
authors.forename: Pei-Chih
authors.initials: PC
authors.lastname: Lu
authors.forename: H Eugene
authors.initials: HE
authors.lastname: Liu
mesh_terms: D000107:Acetylation; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D016022:Case-Control Studies; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors