Admixture mapping of lung cancer in 1812 African-Americans

Ann G Schwartz, Angela S Wenzlaff, Cathryn H Bock, Julie J Ruterbusch, Wei Chen, Michele L Cote, Amanda S Artis, Alison L Van Dyke, Susan J Land, Curtis C Harris, Sharon R Pine, Margaret R Spitz, Christopher I Amos, Albert M Levin, Paul M McKeigue

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)312-317
Number of pages6
JournalCarcinogenesis
Volume32
Issue number3
DOIs
Publication statusPublished - Mar 2011

Keywords

  • Adenocarcinoma
  • African Americans
  • Aged
  • Carcinoma, Non-Small-Cell Lung
  • Carcinoma, Squamous Cell
  • Case-Control Studies
  • DNA, Neoplasm
  • European Continental Ancestry Group
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Lung Neoplasms
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Small Cell Lung Carcinoma
  • Smoking

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