title: Metabolic gene polymorphisms and lung cancer risk in non-smokers. An update of the GSEC study.
abstract: BACKGROUND
  Since genetic factors may play an important role in lung cancer development at low dose carcinogen exposure, non-smokers are a good model to study genetic susceptibility and its interaction with environmental factors.
  
  
  METHODS
  We evaluated the role of the metabolic gene polymorphisms CYP1A1MspI, CYP1A1Ile462Val, GSTM1, and GSTT1 in non-smoker lung cancer patients from the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC). Non-smokers (defined as subjects who never smoked on a regular basis) were selected from the GSEC database. We pooled the raw data from 21 case-control studies for a total of 2764 Caucasians (555 cases and 2209 controls) and 383 Asians (113 cases and 270 controls). Tests of heterogeneity and of inclusion bias were performed.
  
  
  RESULTS
  A significant association between lung cancer and CYP1A1Ile462Val polymorphism was observed in Caucasians (adjusted OR=2.04, 95% CI 1.17-3.54). GSTT1 deletion seems to be a risk factor for lung cancer in Caucasian non smokers only when the analysis was restricted to studies including healthy controls (adjusted OR=1.66, 95% CI 1.12-2.46). A protective effect on lung cancer was observed with the combination of CYP1A1 wild type, GSTM1 null, and GSTT1 non-null genotypes. None of the analysed polymorphisms were associated with lung cancer in Asian non-smokers.
  
  
  CONCLUSIONS
  Our analysis confirms previous findings that CYP1A1Ile462Val polymorphism may play a role in lung carcinogenesis in Caucasian non-smokers.
authors: Fondazione Policlinico IRCCS, Molecular and Genetic Epidemiology Unit, via Pace 9, 20122-Milano, Italy.
authors: Sara
authors: S
authors: Raimondi
authors: Paolo
authors: P
authors: Boffetta
authors: Sisko
authors: S
authors: Anttila
authors: Jürgen
authors: J
authors: Bröckmoller
authors: Dorota
authors: D
authors: Butkiewicz
authors: Ingolf
authors: I
authors: Cascorbi
authors: Margie L
authors: ML
authors: Clapper
authors: Tommaso A
authors: TA
authors: Dragani
authors: Seymour
authors: S
authors: Garte
authors: Andre
authors: A
authors: Gsur
authors: Gerald
authors: G
authors: Haidinger
authors: Ari
authors: A
authors: Hirvonen
authors: Magnus
authors: M
authors: Ingelman-Sundberg
authors: Ivan
authors: I
authors: Kalina
authors: Qing
authors: Q
authors: Lan
authors: Vera Piera
authors: VP
authors: Leoni
authors: Loïc
authors: L
authors: Le Marchand
authors: Stephanie J
authors: SJ
authors: London
authors: Monica
authors: M
authors: Neri
authors: Andrew C
authors: AC
authors: Povey
authors: Agneta
authors: A
authors: Rannug
authors: Edyta
authors: E
authors: Reszka
authors: David
authors: D
authors: Ryberg
authors: Angela
authors: A
authors: Risch
authors: Marjorie
authors: M
authors: Romkes
authors: Alberto
authors: A
authors: Ruano-Ravina
authors: Bernadette
authors: B
authors: Schoket
authors: Monica
authors: M
authors: Spinola
authors: Haruhiko
authors: H
authors: Sugimura
authors: Xifeng
authors: X
authors: Wu
authors: Emanuela
authors: E
authors: Taioli
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics; D019943:Amino Acid Substitution; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004781:Environmental Exposure; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D044469:Racial Groups; D016540:Smoking Cessation; D014481:United States
chemical_list: D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1