title: Fanconi anemia genes in lung adenocarcinoma- a pathway-wide study on cancer susceptibility.
abstract: BACKGROUND
  Carcinogens in cigarette smoke can induce the formation of DNA-DNA cross-links, which are repaired by the Fanconi anemia (FA) pathway, and it is tempting to speculate that this pathway is involved in lung tumorigenesis. This study is to determine whether genetic polymorphism of the FA genes is associated with an elevated risk of lung adenocarcinoma, and whether the association between genotypes and risk is modified by exposure to cigarette smoke.
  
  
  METHODS
  This case-control study genotyped 53 single-nucleotide polymorphisms (SNPs) in FA genes in 709 patients (354 males and 355 females) with lung adenocarcinoma and in 726 cancer-free individuals (339 males and 387 females). Genotypic frequencies of SNPs were compared between cases and controls to identify important FA genes associated with cancer susceptibility. Joint effects in determining cancer risk contributed by genes and smoking-related risk factors and by multiple genes involved in different FA subpathways were evaluated by multivariate regression analysis and stratified analysis. All analyses were performed on males and females separately, and the comparison of results was considered a way of examining the validity of study findings.
  
  
  RESULTS
  Lung adenocarcinomas in both male and female patients were associated with (a) genotypic polymorphisms of FANCC and FANCD1; (b) a combined effect of harboring a higher number of high-risk genotypes and smoking/passive smoking; (c) specific interactions of multiple genes, proteins encoded by which have been known to work jointly within the FA pathway.
  
  
  CONCLUSIONS
  Genetic polymorphism of the FA genes is associated with inter-individual susceptibility to lung adenocarcinoma.
authors: Genomics Research Center, Taipei, Taiwan. yangsyswim@gmail.com.|Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan. yangsyswim@gmail.com.
authors: Shi-Yi
authors: SY
authors: Yang
authors: Institute of Biomedical Sciences, Taipei, Taiwan. chiani@ibms.sinica.edu.tw.
authors: Chia-Ni
authors: CN
authors: Hsiung
authors: Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan. d95842003@ntu.edu.tw.
authors: Yao-Jen
authors: YJ
authors: Li
authors: Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan. august@vghtc.gov.tw.
authors: Gee-Chen
authors: GC
authors: Chang
authors: Department of Pulmonary and Critical Care, Chang Gung Memorial Hospital, Lincou, Taiwan. chestmed@cgms.org.tw.
authors: Ying-Huang
authors: YH
authors: Tsai
authors: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. tuff.chen@msa.hinet.net.
authors: Kuan-Yu
authors: KY
authors: Chen
authors: Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. shyang@kmu.edu.tw.
authors: Ming-Shyan
authors: MS
authors: Huang
authors: Department of Internal Medicine, National Cheng Kung University Hospital and College of Medicine, Tainan, Taiwan. sunnysu@mail.ncku.edu.tw.
authors: Wu-Chou
authors: WC
authors: Su
authors: Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan. ymchen@vghtpe.gov.tw.
authors: Yuh-Min
authors: YM
authors: Chen
authors: Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan. hsiung@nhri.org.tw.
authors: Chao A
authors: CA
authors: Hsiung
authors: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. pcyang@ntu.edu.tw.
authors: Pan-Chyr
authors: PC
authors: Yang
authors: Genomics Research Center, Taipei, Taiwan. chencj@gate.sinica.edu.tw.|Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan. chencj@gate.sinica.edu.tw.
authors: Chien-Jen
authors: CJ
authors: Chen
authors: Institute of Biomedical Sciences, Taipei, Taiwan. peiei@gate.sinica.edu.tw.|Taiwan Biobank, Taipei, Taiwan. peiei@gate.sinica.edu.tw.
authors: Pei-Ei
authors: PE
authors: Wu
authors: Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. doc20106@ndmctsgh.edu.tw.
authors: Jyh-Cherng
authors: JC
authors: Yu
authors: Institute of Biomedical Sciences, Taipei, Taiwan. bmcys@ibms.sinica.edu.tw.|Taiwan Biobank, Taipei, Taiwan. bmcys@ibms.sinica.edu.tw.|Life Science Library, Academia Sinica, Taipei, Taiwan. bmcys@ibms.sinica.edu.tw.|Graduate Institute of Environmental Science, China Medical University, Taichung, Taiwan. bmcys@ibms.sinica.edu.tw.
authors: Chen-Yang
authors: CY
authors: Shen
authors: Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. hmh0823@gmail.com.
authors: Huan-Ming
authors: HM
authors: Hsu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D052218:Fanconi Anemia Complementation Group C Protein / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human; C497651:FANCC protein, human; D052218:Fanconi Anemia Complementation Group C Protein