Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1.
To identify risk variants for lung cancer, we conducted a multistage genome-wide association study. In the discovery phase, we analyzed 315,450 tagging SNPs in 1,154 current and former (ever) smoking cases of European ancestry and 1,137 frequency-matched, ever-smoking controls from Houston, Texas. For replication, we evaluated the ten SNPs most significantly associated with lung cancer in an additional 711 cases and 632 controls from Texas and 2,013 cases and 3,062 controls from the UK. Two SNPs, rs1051730 and rs8034191, mapping to a region of strong linkage disequilibrium within 15q25.1 containing PSMA4 and the nicotinic acetylcholine receptor subunit genes CHRNA3 and CHRNA5, were significantly associated with risk in both replication sets. Combined analysis yielded odds ratios of 1.32 (P < 1 x 10(-17)) for both SNPs. Haplotype analysis was consistent with there being a single risk variant in this region. We conclude that variation in a region of 15q25.1 containing nicotinic acetylcholine receptors genes contributes to lung cancer risk.
Amos
Christopher I
CI
Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. camos@mdanderson.org
Wu
Xifeng
X
Broderick
Peter
P
Gorlov
Ivan P
IP
Gu
Jian
J
Eisen
Timothy
T
Dong
Qiong
Q
Zhang
Qing
Q
Gu
Xiangjun
X
Vijayakrishnan
Jayaram
J
Sullivan
Kate
K
Matakidou
Athena
A
Wang
Yufei
Y
Mills
Gordon
G
Doheny
Kimberly
K
Tsai
Ya-Yu
YY
Chen
Wei Vivien
WV
Shete
Sanjay
S
Spitz
Margaret R
MR
Houlston
Richard S
RS
D000368:Aged; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D003546:Cysteine Endopeptidases / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D015894:Genome, Human; D006239:Haplotypes; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics*
D003546:Cysteine Endopeptidases; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; C447158:CHRNA5 protein, human; C488661:alpha4 subunit, proteasome 20S, human