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Admixture mapping of lung cancer in 1812 African-Americans.

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.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Schwartz AG,Wenzlaff AS,Bock CH,Ruterbusch JJ,Chen W,Cote ML,Artis AS,Van Dyke AL,Land SJ,Harris CC,Pine SR,Spitz MR,Amos CI,Levin AM,McKeigue PM

doi

10.1093/carcin/bgq252

subject

Has Abstract

pub_date

2011-03-01 00:00:00

pages

312-7

issue

3

eissn

0143-3334

issn

1460-2180

pii

bgq252

journal_volume

32

pub_type

杂志文章

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