Supplementary Figure 2 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

Walsh, Kyle M.; Gorlov, Ivan P.; Hansen, Helen M.; Wu, Xifeng; Spitz, Margaret R.; Zhang, Huifeng; Lu, Emily Y.; Wenzlaff, Angela S.; Sison, Jennette D.; Wei, Chongjuan; Lloyd, Stacy M.; Chen, Wei; Frazier, Marsha L.; Seldin, Michael F.; Bierut, Laura J.; Bracci, Paige M.; Wrensch, Margaret R.; Schwartz, Ann G.; Wiencke, John K.; Amos, Christopher I.

doi:10.1158/1055-9965.22436475.v1

10559965epi121007t-sup-fig2.pdf (561.3 kB)

Supplementary Figure 2 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

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 - 561K, Association of SNPs on chromosome 15q25.1 with lung cancer, with and without adjustment for missense variant rs16969968. Black circles depict association of SNPs with lung cancer, adjusted for sex, age, study site, % African ancestry, % European ancestry, and number of pack-years smoked. Open squares depict association of SNPs with lung cancer, adjusted for sex, age, study site, and % African ancestry, % European ancestry, number of pack-years smoked, AND conditioned on rs16969968 (marked with an X).

History

ARTICLE 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. Cancer Epidemiol Biomarkers Prev; 22(2); 251–60. ©2012 AACR.