Admixture mapping of lung cancer in 1812 African-Americans

Carcinogenesis. 2011 Mar;32(3):312-7. doi: 10.1093/carcin/bgq252. Epub 2010 Nov 29.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Aged
  • Black or African American / genetics*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Squamous Cell / genetics
  • Case-Control Studies
  • DNA, Neoplasm / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide / genetics
  • Risk Factors
  • Small Cell Lung Carcinoma / genetics
  • Smoking / genetics
  • White People / genetics

Substances

  • DNA, Neoplasm