Cumulative Effect of Multiple Loci on Genetic Susceptibility to Familial Lung Cancer
Year: 2010
Type: article
Study design: Observational Study
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.
Institutions: National Institutes of Health, Mayo Clinic, The University of Texas MD Anderson Cancer Center, National Human Genome Research Institute, The Barbara Ann Karmanos Cancer Institute, National Cancer Institute, University of Cincinnati, Louisiana State University Health Sciences Center New Orleans, The University of Texas Southwestern Medical Center, University of Toledo
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: G1176074671, MECHANISM OF MOUSE LUNG CARCINOGENESIS, G148520442, Positional Cloning of the Pas 1 QTL in mice, DETERM OF GEN SUSCEPTIBILITY LUNG CANCER, G1826254640, G2426690924, G247409761, Genetic Basis of Lung Tumor Progression in Mice, IDENTIFICATION OF LUNG CANCER SUSCEPTIBILITY GENES, Alpha-1 AD Carriers and Lung Cancer Risk, G3193254293, Genetic Epidemiology of Lung Cancer, G3383439295, Center for Environmental Genetics, G420024314, SEER RRSS #4: Cancer in Arab American Estimating Rates and Fostering Research, Molecular genetics of Mouse Lung Tumors, Identification of Pulmonary Lung Tumor Resistance 1 QTL Candidates, G5792927302, DEVELOPMENT OF LUNG CANCER EPIDEMIOLOGY RESEARCH, G7199811198, G872334548, G883206123, Mayo Clinic Comprehensive Cancer Center Support Grant, CANCER CENTER SUPPORT GRANT, G995644284
OpenAlex ID: W2136985018