title: EGFR polymorphisms, hormone replacement therapy and lung adenocarcinoma risk: analysis from a genome-wide association study in never-smoking women.
abstract: Hormone replacement therapy (HRT) and epidermal growth factor receptor (EGFR) single nucleotide polymorphisms (SNPs) have been reported as risk factors for lung cancer in never smokers. We investigate the interaction of EGFR SNPs and HRT for lung adenocarcinoma risk in never-smoking women. This study included 532 never-smoking female lung adenocarcinoma patients and 532 controls, with EGFR SNPs retrieved from a genome-wide association study. The associations of EGFR SNPs with the lung adenocarcinoma risk were estimated by multivariate-adjusted logistic regression. The Haploview program was used to select tagged EGFR SNPs interacted with HRT and construct haplotype blocks. The Benjamini and Hochberg method was used to reduce the multiple testing effects. Among 84 EGFR SNPs retrieved, 11 tagging EGFR SNPs showed an interaction with HRT and lung adenocarcinoma risk, which were mostly located near the tyrosine kinase domain. Eight of the tagged SNPs were in two haplotype blocks. The interactions between HRT and numbers of protective EGFR SNP genotypes are significant in both blocks (P for interaction = 0.0004 and 0.0032, respectively). A trend of decrease in lung adenocarcinoma risk was found in subjects with HRT harboring an increasing number of protective EGFR SNP genotypes in both blocks (P = 0.0032 and 0.0046, respectively). In conclusion, HRT use may modify the association of EGFR SNPs with lung adenocarcinoma risk. The EGFR SNPs have a cumulative effect on decreasing lung adenocarcinoma risk in never-smoking women with HRT use.
authors.affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University,  Taipei 100, Taiwan.
authors.forename: Kuan-Yu
authors.initials: KY
authors.lastname: Chen
authors.forename: Chin-Fu
authors.initials: CF
authors.lastname: Hsiao
authors.forename: Gee-Chen
authors.initials: GC
authors.lastname: Chang
authors.forename: Ying-Huang
authors.initials: YH
authors.lastname: Tsai
authors.forename: Wu-Chou
authors.initials: WC
authors.lastname: Su
authors.forename: Yuh-Min
authors.initials: YM
authors.lastname: Chen
authors.forename: Ming-Shyan
authors.initials: MS
authors.lastname: Huang
authors.forename: Chao A
authors.initials: CA
authors.lastname: Hsiung
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
authors.forename: Pan-Chyr
authors.initials: PC
authors.lastname: Yang
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000368:Aged; D016022:Case-Control Studies; D066246:ErbB Receptors / Q000235:genetics*; D015914:Estrogen Replacement Therapy; D005260:Female; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D011372:Progestins / Q000627:therapeutic use; D012307:Risk Factors; D012907:Smoking
chemical_list: D011372:Progestins; D066246:ErbB Receptors