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
| Autor: | Laura J. Bierut, Helen M. Hansen, Paige M. Bracci, Stacy M. Lloyd, Ivan P. Gorlov, Kyle M. Walsh, Huifeng Zhang, Michael F. Seldin, Marsha L. Frazier, Margaret R. Spitz, John K. Wiencke, Jennette D. Sison, Angela S. Wenzlaff, Ann G. Schwartz, Margaret Wrensch, Chongjuan Wei, Christopher I. Amos, Emily Y. Lu, Xifeng Wu, Wei V. Chen |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Oncology medicine.medical_specialty Linkage disequilibrium Pathology Lung Neoplasms Epidemiology Nerve Tissue Proteins Genome-wide association study Single-nucleotide polymorphism Adenocarcinoma Receptors Nicotinic Biology Polymerase Chain Reaction Polymorphism Single Nucleotide Linkage Disequilibrium Article Risk Factors Internal medicine Genotype Biomarkers Tumor medicine Humans Genetic Predisposition to Disease Lung cancer Lung Telomerase Aged Genetic association Chromosomes Human Pair 15 Chromosome Mapping Proteins Middle Aged Prognosis medicine.disease Small Cell Lung Carcinoma Lung cancer susceptibility Black or African American Case-Control Studies Carcinoma Squamous Cell Chromosomes Human Pair 5 Chromosomes Human Pair 6 Female Genome-Wide Association Study |
| Zdroj: | Cancer Epidemiology, Biomarkers & Prevention. 22:251-260 |
| ISSN: | 1538-7755 1055-9965 |
| DOI: | 10.1158/1055-9965.epi-12-1007-t |
| Popis: | 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. Cancer Epidemiol Biomarkers Prev; 22(2); 251–60. ©2012 AACR. |
| Databáze: | OpenAIRE |
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