Year: 2010
Type: article
Study design: Observational Study
Abstract: Lung cancer continues to be the leading cause of cancer death in the USA and the best example of a cancer with undisputed evidence of environmental risk. However, a genetic contribution to lung cancer has also been demonstrated by studies of familial aggregation, family-based linkage, candidate gene studies and most recently genome-wide association studies (GWAS). The African-American population has been underrepresented in these genetic studies and has patterns of cigarette use and linkage disequilibrium that differ from patterns in other populations. Therefore, studies in African-Americans can provide complementary data to localize lung cancer susceptibility genes and explore smoking dependence-related genes. We used admixture mapping to further characterize genetic risk of lung cancer in a series of 837 African-American lung cancer cases and 975 African-American controls genotyped at 1344 ancestry informative single-nucleotide polymorphisms. Both case-only and case-control analyses were conducted using ADMIXMAP adjusted for age, sex, pack-years of smoking, family history of lung cancer, history of emphysema and study site. In case-only analyses, excess European ancestry was observed over a wide region on chromosome 1 with the largest excess seen at rs6587361 for non-small-cell lung cancer (NSCLC) (Z-score = -4.33; P = 1.5 × 10⁻⁵) and for women with NSCLC (Z-score = -4.82; P = 1.4 × 10⁻⁶). Excess African ancestry was also observed on chromosome 3q with a peak Z-score of 3.33 (P = 0.0009) at rs181696 among ever smokers with NSCLC. These results add to the findings from the GWAS in Caucasian populations and suggest novel regions of interest.
Source: Carcinogenesis
Institutions: Wayne State University, The Barbara Ann Karmanos Cancer Institute, National Institutes of Health, National Cancer Institute, Center for Cancer Research, The University of Texas MD Anderson Cancer Center, Henry Ford Health, Western General Hospital, MRC Human Genetics Unit, University of Edinburgh
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: G122526512, G1394878971, G148520442, G1767672275, Genetic Epidemiology of Lung Cancer, G187063468, G1876780871, G3453310768, G3808507967, G420024314, G4343711164, G4509978856, G452865728, Transdisciplinary Research in Cancer of the Lung (TRICL), G4808091200, Adenocarcinoma of the Lung: role of NNK susceptibility, SEER RRSS #4: Cancer in Arab American Estimating Rates and Fostering Research, G5692528997, G6050486683, G6150611542, High Density Association Analysis of Lung Cancer, G8016623132, G8315719417, Genetic Susceptibility for Lung Cancer in African Americans, G886698072, G9000020586, G9000131883, CANCER CENTER SUPPORT GRANT
OpenAlex ID: W2168631446