Fine-mapping of the 5p15.33, 6p22.1-p21.31, and 15q25.1 Regions Identifies Functional and Histology-Specific Lung Cancer Susceptibility Loci in African-Americans
Year: 2012
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Genome-wide association studies of European and East Asian populations have identified lung cancer susceptibility loci on chromosomes 5p15.33, 6p22.1-p21.31, and 15q25.1. We investigated whether these regions contain lung cancer susceptibly loci in African-Americans and refined previous association signals by using the reduced linkage disequilibrium observed in African-Americans. METHODS: 1,308 African-American cases and 1,241 African-American controls from 3 centers were genotyped for 760 single-nucleotide polymorphisms (SNP) spanning 3 regions, and additional SNP imputation was carried out. Associations between polymorphisms and lung cancer risk were estimated using logistic regression, stratified by tumor histology where appropriate. RESULTS: The strongest associations were observed on 15q25.1 in/near CHRNA5, including a missense substitution [rs16969968: OR, 1.57; 95% confidence interval (CI), 1.25-1.97; P, 1.1 × 10(-4)) and variants in the 5'-UTR. Associations on 6p22.1-p21.31 were histology specific and included a missense variant in BAT2 associated with squamous cell carcinoma (rs2736158: OR, 0.64; 95% CI, 0.48-0.85; P, 1.82 × 10(-3)). Associations on 5p15.33 were detected near TERT, the strongest of which was rs2735940 (OR, 0.82; 95% CI, 0.73-0.93; P, 1.1 × 10(-3)). This association was stronger among cases with adenocarcinoma (OR, 0.75; 95% CI, 0.65-0.86; P, 8.1 × 10(-5)). CONCLUSIONS: Polymorphisms in 5p15.33, 6p22.1-p21.31, and 15q25.1 are associated with lung cancer in African-Americans. Variants on 5p15.33 are stronger risk factors for adenocarcinoma and variants on 6p21.33 associated only with squamous cell carcinoma. IMPACT: Results implicate the BAT2, TERT, and CHRNA5 genes in the pathogenesis of specific lung cancer histologies.
Authors: Kyle M. Walsh, Ivan P. Gorlov, Helen M. Hansen, Xifeng Wu, Margaret R. Spitz, Huifeng Zhang, Emily Y. Lu, Angela S. Wenzlaff, Jennette D. Sison, Chongjuan Wei, Stacy M. Lloyd, Wei Chen, Marsha L. Frazier, Michael F. Seldin, Laura J. Bierut, Paige M. Bracci, Margaret R. Wrensch, Ann G. Schwartz, John K. Wiencke, Christopher I. Amos
Institutions: The University of Texas MD Anderson Cancer Center, University of California, San Francisco, Baylor College of Medicine, Wayne State University, Washington University in St. Louis, The Barbara Ann Karmanos Cancer Institute, UCSF Helen Diller Family Comprehensive Cancer Center, Dan L Duncan Comprehensive Cancer Center, University of California, Davis
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: G122526512, G1311563309, G1828710530, Genetic Epidemiology of Lung Cancer, G3144202555, G3193254293, G3699908246, G370871742, SEER RRSS #4: Cancer in Arab American Estimating Rates and Fostering Research, G532587972, High Density Association Analysis of Lung Cancer, G7335139911, Training in Molecular& Genetic Epidemiology of Cancer, Genetic Susceptibility for Lung Cancer in African Americans, CANCER CENTER SUPPORT GRANT, G931892564, G932583763
OpenAlex ID: W2135864428