title: EGFR exon 19 in-frame deletion and polymorphisms of DNA repair genes in never-smoking female lung adenocarcinoma patients.
abstract: We explored potential associations between genetic polymorphisms in genes related to DNA repair and detoxification metabolism and epidermal growth factor receptor (EGFR) mutations in a cohort of 410 never-smoking patients with lung adenocarcinoma. Multivariate-adjusted odds ratios (aORs) and corresponding 95% confidence intervals (CI) of EGFR mutation status in association with the genotypes of DNA repair and detoxification metabolism genes were evaluated using logistic regression analysis. We found an association between in-frame deletion in EGFR exon 19 and a single nucleotide polymorphism (SNP) rs1800566C/T located in NQO1 (aOR, 2.2 with 95% CI, 1.0-4.8) in female never-smokers. The SNP rs744154C/G in ERCC4 was also associated with the EGFR exon 19 in-frame deletion both in never-smokers (aOR, 1.7 with 95% CI, 1.0-3.0) and female never-smokers (aOR, 1.9 with 95% CI, 1.0-3.6). Although the association was marginally significant in multivariate logistic regression analysis, the A/A genotype of rs1047840 in EXO1 was associated with a 7.6-fold increase in the occurrence of the EGFR exon 19 in-frame deletion in female never-smokers. Moreover, risk alleles in NQO1, ERCC4 and EXO1 were associated with an increasing aOR of the EGFR exon 19 in-frame deletion both in never-smokers (p = 0.007 for trend) and female never-smokers (p = 0.002 for trend). Our findings suggest that the in-frame deletion in EGFR exon 19 is associated with polymorphisms in DNA repair and detoxification metabolism genes in never-smoking lung adenocarcinoma patients, especially in females.
authors.affiliation: Genomics Research Center, Academia Sinica, Taiwan.
authors.forename: Shi-Yi
authors.initials: SY
authors.lastname: Yang
authors.forename: Tsung-Ying
authors.initials: TY
authors.lastname: Yang
authors.forename: Yao-Jen
authors.initials: YJ
authors.lastname: Li
authors.forename: Kun-Chieh
authors.initials: KC
authors.lastname: Chen
authors.forename: Kuo-Meng
authors.initials: KM
authors.lastname: Liao
authors.forename: Kuo-Hsuan
authors.initials: KH
authors.lastname: Hsu
authors.forename: Chi-Ren
authors.initials: CR
authors.lastname: Tsai
authors.forename: Chih-Yi
authors.initials: CY
authors.lastname: Chen
authors.forename: Chung-Ping
authors.initials: CP
authors.lastname: Hsu
authors.forename: Jiun-Yi
authors.initials: JY
authors.lastname: Hsia
authors.forename: Cheng-Yen
authors.initials: CY
authors.lastname: Chuang
authors.forename: Ying-Huang
authors.initials: YH
authors.lastname: Tsai
authors.forename: Kuan-Yu
authors.initials: KY
authors.lastname: Chen
authors.forename: Ming-Shyan
authors.initials: MS
authors.lastname: Huang
authors.forename: Wu-Chou
authors.initials: WC
authors.lastname: Su
authors.forename: Yuh-Min
authors.initials: YM
authors.lastname: Chen
authors.forename: Chao A
authors.initials: CA
authors.lastname: Hsiung
authors.forename: Chen-Yang
authors.initials: CY
authors.lastname: Shen
authors.forename: Gee-Chen
authors.initials: GC
authors.lastname: Chang
authors.forename: Pan-Chyr
authors.initials: PC
authors.lastname: Yang
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D004252:DNA Mutational Analysis; D004260:DNA Repair / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005090:Exodeoxyribonucleases / Q000235:genetics; D005091:Exons; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D051718:MutS Homolog 2 Protein / Q000235:genetics; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017384:Sequence Deletion; D012737:Sex Factors; D012907:Smoking
chemical_list: D004268:DNA-Binding Proteins; C095888:xeroderma pigmentosum group F protein; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D066246:ErbB Receptors; C114331:EXO1 protein, human; D005090:Exodeoxyribonucleases; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes