title: A functional polymorphism in CSF1R gene is a novel susceptibility marker for lung cancer among never-smoking females.
abstract: BACKGROUND
  It has been estimated that the proportion of never-smokers among females with lung cancer is 53% worldwide and 75% in Korea. We conducted a two-stage study to identify genetic factors responsible for lung cancer susceptibility in female never-smokers.
  
  
  METHODS
  In a discovery set, 1969 potentially functional single nucleotide polymorphisms (SNPs) of 1151 genes, which were related to cancer development and progression, were evaluated using the Affymetrix custom-made GeneChip in 181 female never-smokers with lung cancer and 179 controls. A replication study was performed on an independent cohort of 596 cases and 1194 healthy controls.
  
  
  RESULTS
  Sixteen SNPs with p < 0.05 for genotype distribution in the discovery set were enrolled in the replication study. Among 16 SNPs, three SNPs (colony-stimulating factor 1 receptor [CSF1R] rs10079250A>G, tumor protein p63 [TP63] rs7631358G>A, and corepressor interacting with RBPJ 1 [CIR1] rs13009079T>C) were found to be significantly associated with lung cancer in the same direction as the discovery set. Homology-based model for CSF1R indicated that the rs10079250A>G leads to increased positive charge of CSF-binding region of CSF1R, thereby increasing the chance of binding between CSF and CSF1R. In addition, this SNP was found to increase the phosphorylation of a mitogen-activated protein kinase, JNK.
  
  
  CONCLUSIONS
  Our results suggest that the three SNPs, particularly CSF1R rs10079250, may contribute to lung cancer susceptibility in never-smoking females.
authors.affiliation: *Department of Biochemistry and Cell Biology and †Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea; ‡Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Korea; §Biostatistics Center, School of Medicine, Kyungpook National University, Daegu, Korea; ‖D&P Biotech, Inc., Daegu, Korea; ¶Department of Thoracic and Cardiovascular Surgery, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea; #Genomic Medicine Institute, Cancer Research Institute, Seoul National University, Seoul, Korea; **Department of Environmental Health, Graduate School of Public Health, Seoul National University, Seoul, Korea; ††Department of Preventive Medicine, Seoul National University School of Medicine, Seoul, Korea; ‡‡Division of Oncology/Hematology, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea; and §§Cancer Research Institute, Korea University, Seoul, Korea.
authors.forename: Hyo-Gyoung
authors.initials: HG
authors.lastname: Kang
authors.forename: Shin Yup
authors.initials: SY
authors.lastname: Lee
authors.forename: Hyo-Sung
authors.initials: HS
authors.lastname: Jeon
authors.forename: Yi Young
authors.initials: YY
authors.lastname: Choi
authors.forename: Soyoun
authors.initials: S
authors.lastname: Kim
authors.forename: Won Kee
authors.initials: WK
authors.lastname: Lee
authors.forename: Hyun Chul
authors.initials: HC
authors.lastname: Lee
authors.forename: Jin Eun
authors.initials: JE
authors.lastname: Choi
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Bae
authors.forename: Seung Soo
authors.initials: SS
authors.lastname: Yoo
authors.forename: Jaehee
authors.initials: J
authors.lastname: Lee
authors.forename: Seung Ick
authors.initials: SI
authors.lastname: Cha
authors.forename: Chang Ho
authors.initials: CH
authors.lastname: Kim
authors.forename: Myung Hoon
authors.initials: MH
authors.lastname: Lee
authors.forename: Young Tae
authors.initials: YT
authors.lastname: Kim
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Yun-Chul
authors.initials: YC
authors.lastname: Hong
authors.forename: Yeul Hong
authors.initials: YH
authors.lastname: Kim
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
mesh_terms: D016022:Case-Control Studies; D045744:Cell Line, Tumor; D005260:Female; D020022:Genetic Predisposition to Disease; D057809:HEK293 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics*
chemical_list: D016186:Receptor, Macrophage Colony-Stimulating Factor