Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer.
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Date
2014-09-11Author
Wang, Y
McKay, JD
Rafnar, T
Wang, Z
Timofeeva, MN
Broderick, P
Zong, X
Laplana, M
Wei, Y
Han, Y
Lloyd, A
Delahaye-Sourdeix, M
Chubb, D
Gaborieau, V
Wheeler, W
Chatterjee, N
Thorleifsson, G
Sulem, P
Liu, G
Kaaks, R
Henrion, M
Kinnersley, B
Vallée, M
LeCalvez-Kelm, F
Stevens, VL
Gapstur, SM
Chen, WV
Zaridze, D
Szeszenia-Dabrowska, N
Lissowska, J
Rudnai, P
Fabianova, E
Mates, D
Bencko, V
Foretova, L
Janout, V
Krokan, HE
Gabrielsen, ME
Skorpen, F
Vatten, L
Njølstad, I
Chen, C
Goodman, G
Benhamou, S
Vooder, T
Välk, K
Nelis, M
Metspalu, A
Lener, M
Lubiński, J
Johansson, M
Vineis, P
Agudo, A
Clavel-Chapelon, F
Bueno-de-Mesquita, HB
Trichopoulos, D
Khaw, K-T
Johansson, M
Weiderpass, E
Tjønneland, A
Riboli, E
Lathrop, M
Scelo, G
Albanes, D
Caporaso, NE
Ye, Y
Gu, J
Wu, X
Spitz, MR
Dienemann, H
Rosenberger, A
Su, L
Matakidou, A
Eisen, T
Stefansson, K
Risch, A
Chanock, SJ
Christiani, DC
Hung, RJ
Brennan, P
Landi, MT
Houlston, RS
Amos, CI
Type
Journal Article
Metadata
Show full item recordAbstract
We conducted imputation to the 1000 Genomes Project of four genome-wide association studies of lung cancer in populations of European ancestry (11,348 cases and 15,861 controls) and genotyped an additional 10,246 cases and 38,295 controls for follow-up. We identified large-effect genome-wide associations for squamous lung cancer with the rare variants BRCA2 p.Lys3326X (rs11571833, odds ratio (OR) = 2.47, P = 4.74 × 10(-20)) and CHEK2 p.Ile157Thr (rs17879961, OR = 0.38, P = 1.27 × 10(-13)). We also showed an association between common variation at 3q28 (TP63, rs13314271, OR = 1.13, P = 7.22 × 10(-10)) and lung adenocarcinoma that had been previously reported only in Asians. These findings provide further evidence for inherited genetic susceptibility to lung cancer and its biological basis. Additionally, our analysis demonstrates that imputation can identify rare disease-causing variants with substantive effects on cancer risk from preexisting genome-wide association study data.
Collections
Subject
Humans
Adenocarcinoma
Carcinoma, Squamous Cell
Lung Neoplasms
Genetic Predisposition to Disease
BRCA2 Protein
Prognosis
Risk Factors
Case-Control Studies
Polymorphism, Single Nucleotide
Meta-Analysis as Topic
Genome-Wide Association Study
Checkpoint Kinase 2
Research team
Cancer Genomics
Molecular & Population Genetics
Language
eng
Date accepted
2014-05-08
License start date
2014-07
Citation
Nature genetics, 2014, 46 (7), pp. 736 - 741
Publisher
NATURE PUBLISHING GROUP