title: A second genetic variant on chromosome 15q24-25.1 associates with lung cancer.
abstract: A common variant on chromosomal region 15q24-25.1, marked by rs1051730, was found to be associated with lung cancer risk. Here, we attempted to confirm the second variant on 15q24-25.1 in several large sporadic lung cancer populations and determined what percentage of additional risk for lung cancer is due to the genetic effect of the second variant. SNPs rs1051730 and rs481134 were genotyped in 2,818 lung cancer cases and 2,766 controls from four populations. Joint analysis of these two variants (rs1051730 and rs481134) on 15q24-25.1 identified three major haplotypes (G_T, A_C, and G_C) and provided stronger evidence for association of 15q24-25.1 with lung cancer (P = 9.72 x 10(-9)). These two variants represent three levels of risk associated with lung cancer. The most common haplotype G_T is neutral; the haplotype A_C is associated with increased risk for lung cancer with 5.0% higher frequency in cases than in controls [P = 1.68 x 10(-7); odds ratio (OR), 1.24; 95% confidence interval (95% CI), 1.14-1.35]; whereas the haplotype G_C is associated with reduced risk for lung cancer with 4.4% lower frequency in cases than in controls (P = 7.39 x 10(-7); OR, 0.80; 95% CI, 0.73-0.87). We further showed that these two genetic variants on 15q24-25.1 independently influence lung cancer risk (rs1051730: P = 4.42 x 10(-11); OR, 1.60; 95% CI, 1.46-1.74; rs481134: P = 7.01 x 10(-4); OR, 0.81; 95% CI, 0.72-0.92). The second variant on 15q24-25.1, marked by rs481134, explains an additional 13.2% of population attributable risk for lung cancer.
authors.affiliation: Washington University School of Medicine, St Louis, Missouri 63110, USA.
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Liu
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
authors.forename: Haris G
authors.initials: HG
authors.lastname: Vikis
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.forename: Yian
authors.initials: Y
authors.lastname: Wang
authors.forename: Ann G
authors.initials: AG
authors.lastname: Schwartz
authors.forename: Susan M
authors.initials: SM
authors.lastname: Pinney
authors.forename: Mariza
authors.initials: M
authors.lastname: de Andrade
authors.forename: Adi
authors.initials: A
authors.lastname: Gazdar
authors.forename: Colette
authors.initials: C
authors.lastname: Gaba
authors.forename: Diptasri
authors.initials: D
authors.lastname: Mandal
authors.forename: Juwon
authors.initials: J
authors.lastname: Lee
authors.forename: Elena
authors.initials: E
authors.lastname: Kupert
authors.forename: Daniela
authors.initials: D
authors.lastname: Seminara
authors.forename: John
authors.initials: J
authors.lastname: Minna
authors.forename: Joan E
authors.initials: JE
authors.lastname: Bailey-Wilson
authors.forename: Margaret
authors.initials: M
authors.lastname: Spitz
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.forename: Marshall W
authors.initials: MW
authors.lastname: Anderson
authors.forename: Ming
authors.initials: M
authors.lastname: You
mesh_terms: D001741:Black or African American; D000483:Alleles; D016022:Case-Control Studies; D002884:Chromosomes, Human, Pair 15; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D015233:Models, Statistical; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D012306:Risk; D044465:White People
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