Admixture mapping of lung cancer in 1812 African-Americans.
- Authors
- Schwartz, Ann G; Wenzlaff, Angela S; Bock, Cathryn H; Ruterbusch, Julie J; Chen, Wei; Cote, Michele L; Artis, Amanda S; Van Dyke, Alison L; Land, Susan J; Harris, Curtis C; Pine, Sharon R; Spitz, Margaret R; Amos, Christopher I; Levin, Albert M; McKeigue, Paul M
- Year
- 2011
- Journal
- Carcinogenesis
- PMID
- 21115650
- DOI
- 10.1093/carcin/bgq252
- PMCID
- PMC3047238
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.
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