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A second genetic variant on chromosome 15q24-25.1 associates with lung cancer. Cancer Res 2010 Apr 15;70(8):3128-35

Date

04/17/2010

Pubmed ID

20395203

Pubmed Central ID

PMC3378320

DOI

10.1158/0008-5472.CAN-09-3583

Scopus ID

2-s2.0-77951049337   4 Citations

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.

Author List

Liu P, Yang P, Wu X, Vikis HG, Lu Y, Wang Y, Schwartz AG, Pinney SM, de Andrade M, Gazdar A, Gaba C, Mandal D, Lee J, Kupert E, Seminara D, Minna J, Bailey-Wilson JE, Spitz M, Amos CI, Anderson MW, You M

Authors

Pengyuan Liu PhD Adjunct Professor in the Physiology department at Medical College of Wisconsin
Yian Wang MD, PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Ming You MD, PhD Associate Provost, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

African Americans
Alleles
Case-Control Studies
Chromosomes, Human, Pair 15
European Continental Ancestry Group
Gene Expression Regulation, Neoplastic
Genetic Variation
Haplotypes
Humans
Lung Neoplasms
Models, Statistical
Odds Ratio
Polymorphism, Single Nucleotide
Regression Analysis
Risk
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d