American Association for Cancer Research
10559965epi121007t-sup-fig1.pdf (926.15 kB)

Supplementary Figure 1 from 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

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journal contribution
posted on 2023-03-31, 13:43 authored by 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

PDF file - 926K, Triangle plot showing estimated admixture in the African-American case-control population. Estimates were performed using 102 AIMs and data from the International HapMap Project on 167 Yoruban African (Green dots), 165 European (Red dots), 84 Chinese (Yellow dots) and 86 Japanese (Dark Blue dots) founders. The figure depicts ancestry in 1308 African-American lung cancer cases (Pink dots) and 1241 controls (Light Blue dots).



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.

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