Admixture mapping of lung cancer in 1812 African-Americans.
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.
Karmanos Cancer Institute, Detroit, MI 48201, USA. schwarta@karmanos.org
Ann G
AG
Schwartz
Angela S
AS
Wenzlaff
Cathryn H
CH
Bock
Julie J
JJ
Ruterbusch
Wei
W
Chen
Michele L
ML
Cote
Amanda S
AS
Artis
Alison L
AL
Van Dyke
Susan J
SJ
Land
Curtis C
CC
Harris
Sharon R
SR
Pine
Margaret R
MR
Spitz
Christopher I
CI
Amos
Albert M
AM
Levin
Paul M
PM
McKeigue
D000230:Adenocarcinoma / Q000235:genetics; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D016022:Case-Control Studies; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D055752:Small Cell Lung Carcinoma / Q000235:genetics; D012907:Smoking / Q000235:genetics; D044465:White People / Q000235:genetics
D004273:DNA, Neoplasm