title: EGFR L858R mutation and polymorphisms of genes related to estrogen biosynthesis and metabolism in never-smoking female lung adenocarcinoma patients.
abstract: OBJECTIVE
  To assess whether polymorphisms of genes related to estrogen biosynthesis and metabolism are associated with EGFR mutations.
  
  
  METHODS
  We studied 617 patients with lung adenocarcinoma, including 302 never-smoking women. On the basis of multiple candidate genes approach, the effects of polymorphisms of CYP17, CYP19A1, ERα, and COMT in association with the occurrence of EGFR mutations were evaluated using logistic regression analysis.
  
  
  RESULTS
  In female never-smokers, significant associations with EGFR L858R mutation were found for the tetranucleotide (TTTA)(n) repeats in CYP19A1 (odds ratio, 2.6; 95%CI, 1.2-5.7 for 1 or 2 alleles with (TTTA)(n) repeats >7 compared with both alleles with (TTTA)(n) repeats ≤ 7), and the rs2234693 in ERα (OR, 2.1; 95% CI, 1.1-4.0 for C/T and C/C genotypes compared with T/T genotype). The C/C genotype (vs. T/T genotype) of ERα was significantly associated with EGFR L858R mutation (OR, 3.0; 95% CI, 1.1-8.1), in-frame deletion (OR, 2.9; 95% CI, 1.1-7.6) and other mutations (OR, 4.3; 95% CI, 1.3-14.0). The genotype of COMT rs4680 was significantly associated with EGFR L858R mutation in female and male never-smokers showing OR's (95% CI) of 1.8 (1.0-3.2) and 3.6 (1.1-11.3), respectively, for genotypes G/A and G/G compared with genotype A/A. The number of risk alleles of CYP17, CYP19A1, ERα, and COMT was associated with an increasing OR of EGFR L858R mutation in female never-smokers (P = 0.0002 for trend).
  
  
  CONCLUSIONS
  The L858R mutation of EGFR is associated with polymorphisms of genes related to estrogen biosynthesis and metabolism in never-smoking female lung adenocarcinoma patients.
authors.affiliation: Genomics Research Center, College of Public Health, National Taiwan University, Taipei, Taiwan.
authors.forename: Shi-Yi
authors.initials: SY
authors.lastname: Yang
authors.forename: Tsung-Ying
authors.initials: TY
authors.lastname: Yang
authors.forename: Kun-Chieh
authors.initials: KC
authors.lastname: Chen
authors.forename: Yao-Jen
authors.initials: YJ
authors.lastname: Li
authors.forename: Kuo-Hsuan
authors.initials: KH
authors.lastname: Hsu
authors.forename: Chi-Rne
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* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D053898:Biosynthetic Pathways; D002394:Catechol O-Methyltransferase / Q000235:genetics / Q000378:metabolism; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D012907:Smoking; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; D001141:Aromatase; C561410:CYP19A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase; D002394:Catechol O-Methyltransferase; D066246:ErbB Receptors