title: The 18p11.22 locus is associated with never smoker non-small cell lung cancer susceptibility in Korean populations.
abstract: The proportion of never smoker non-small cell lung cancer (NSCLC) in Asia is about 30-40%. Despite the striking demographics and high prevalence of never smoker NSCLC, the exact causes still remain undetermined. Although several genome wide association (GWA) studies were conducted to find susceptibility loci for lung cancer in never smokers, no regions were replicated except for 5p15.33, suggesting locus heterogeneity and different environmental toxic effects. To identify genetic loci associated with susceptibility of lung cancer in never smokers, we performed a GWA analysis using the Affymetrix 6.0 SNP array. For discovery GWA set, we recruited 446 never smoking Korean patients with NSCLC and 497 normal subjects. We tested association of SNPs with lung cancer susceptibility using the Cochran-Armitage trend test. For validation, 39 SNPs were selected from the top 50 SNPs and five additional SNPs were selected in the DAB1 gene region which showed significant associations in the GWA analysis. The validation SNPs were genotyped in an independent sample including 434 patients and 1,000 controls. Among the 44 validation SNPs, two SNPs (rs11080466 and rs11663246) near the APCDD1, NAPG and FAM38B genes in the 18p11.22 region were replicated. P value of rs11080466 was 1.08 × 10(-6) in the combined sets (2.68 × 10(-5) in the discovery set and 2.60 × 10(-3) in the validation set) and odds ratio was 0.68 (0.58-0.79). We observed similar association for rs11663246. Our result suggests the 18p11.22 region as a novel lung cancer susceptibility locus in never smokers.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul 135-710, Korea.
authors.forename: Myung-Ju
authors.initials: MJ
authors.lastname: Ahn
authors.forename: Hong-Hee
authors.initials: HH
authors.lastname: Won
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Lee
authors.forename: Seung-Tae
authors.initials: ST
authors.lastname: Lee
authors.forename: Jong-Mu
authors.initials: JM
authors.lastname: Sun
authors.forename: Yeon Hee
authors.initials: YH
authors.lastname: Park
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Ahn
authors.forename: O Jung
authors.initials: OJ
authors.lastname: Kwon
authors.forename: Hojoong
authors.initials: H
authors.lastname: Kim
authors.forename: Young Mog
authors.initials: YM
authors.lastname: Shim
authors.forename: Jhingook
authors.initials: J
authors.lastname: Kim
authors.forename: Kwhanmien
authors.initials: K
authors.lastname: Kim
authors.forename: Yeul Hong
authors.initials: YH
authors.lastname: Kim
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Keunchil
authors.initials: K
authors.lastname: Park
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007723:Korea; D008175:Lung Neoplasms / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000235:genetics