Fine-Mapping in a Covariate-based Genomewide Linkage Scan of Lung Cancer Susceptibility.

Thursday, October 11, 2012 — Poster Session III
10:00 a.m. – Noon	Natcher Conference Center, Building 45	NHGRI	GEN/GENOM-22

Authors

• C L Simpson
• T Green
• B Doan
• C I Amos
• S M Pinney
• E Y Kupert
• M de Andrade
• P Yang
• A G Schwartz
• P R Fain
• A Gazdar
• J Minna
• J S Wiest
• H Rothschild
• D Mandal
• M You
• T A Coons
• C Gaba
• M W Anderson
• J E Bailey-Wilson

Abstract

Lung cancer (LC) is a leading cause of death in developed countries, with >160,000 US deaths expected in 2012. Environmental risk factors such as smoking and asbestos exposures are well known. However, only 15% of smokers develop LC, suggesting genetic effects or gene-environment (GxE) interactions. We previously mapped a major LC susceptibility locus to 6q23-q25, and discovered a rare risk haplotype in linked families that exhibits GxE interaction between the 6q locus and smoking. Genome-wide association studies have suggested other loci with common alleles of small effect on LC risk. However, these loci do not explain all familial risk of LC, suggesting additional risk alleles exist. We have also found additional susceptibility loci using linkage analysis including environmental covariates, using microsatellites, on 6p (LOD=5.75, 74cM) and 6q (LOD=3.25, 173cM), with novel evidence of linkage on 12q24 (LOD=5.46, 150cM) and 22q11 (LOD=5.19,10cM). Linkage to lung and throat cancer was observed on 9p21 (LOD=4.97, 64cM). Here we present results of a fine-mapping linkage analysis, combining microsatellite data with a dense SNP map. Standard data cleaning methods were applied and allele frequencies estimated from the data. Linkage analyses of LC (adjusting for personal smoking) to the combined dataset using LODPAL will be presented.

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