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Cumulative effect of multiple loci on genetic susceptibility to familial lung cancer. Cancer Epidemiol Biomarkers Prev 2010 Feb;19(2):517-24

Date

02/10/2010

Pubmed ID

20142248

Pubmed Central ID

PMC2846747

DOI

10.1158/1055-9965.EPI-09-0791

Scopus ID

2-s2.0-76149107483   24 Citations

Abstract

BACKGROUND: Genetic factors play important roles in lung cancer susceptibility. In this study, we replicated the association of 5p15.33 and 6p21.33 with familial lung cancer. Taking into account the previously identified genetic susceptibility variants on 6q23-25/RGS17 and 15q24-25.1, we further determined the cumulative association of these four genetic regions and the population attributable risk percent of familial lung cancer they account for.

METHODS: One hundred ninety-four case patients and 219 cancer-free control subjects from the Genetic Epidemiology of Lung Cancer Consortium were used for the association analysis. Each familial case was chosen from one high-risk lung cancer family that has three or more affected members. Single nucleotide polymorphisms (SNP) on chromosomal regions 5p15.33, 6p21.33, 6q23-25/RGS17, and 15q24-25.1 were assessed for their associations with familial lung cancer. The cumulative association of the four chromosomal regions with familial lung cancer was evaluated with the use of a linear logistic model. Population attributable risk percent was calculated for each SNP using risk ratio.

RESULTS: SNP rs31489 showed the strongest evidence of familial lung cancer association on 5p15.33 (P = 2 x 10(-4); odds ratio, 0.57; 95% confidence interval, 0.42-0.77), whereas rs3117582 showed a weak association on 6p21.33 (P = 0.09; odds ratio, 1.47; 95% confidence interval, 0.94-2.31). Analysis of a combination of SNPs from the four regions provided a stronger cumulative association with familial lung cancer (P = 6.70 x 10(-6)) than any individual SNPs. The risk of lung cancer was increased to 3- to 11-fold among those subjects who had at least one copy of risk allele at each region compared with subjects without any of the risk factors. These four genetic regions contribute to a total of 34.6% of familial lung cancer in smokers.

CONCLUSIONS: The SNPs in four chromosomal regions have a cumulative and significant association with familial lung cancer and account for about one-third of the population attributable risk for familial lung cancer.

Author List

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

Chromosomes, Human, Pair 15
Chromosomes, Human, Pair 5
Chromosomes, Human, Pair 6
Female
Genetic Association Studies
Genetic Predisposition to Disease
Humans
Lung Neoplasms
Male
Polymorphism, Single Nucleotide
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d