Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer

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2014
Author
Wang, Yufei
McKay, James D.
Rafnar, Thorunn
Wang, Zhaoming
Timofeeva, Maria N.
Broderick, Peter
Zong, Xuchen
Laplana Lafaja, Marina
Wei, Yongyue
Han, Younghun
Lloyd, Amy
Delahaye-Sourdeix, Manon
Chubb, Daniel
Gaborieau, Valerie
Wheeler, William
Chatterjee, Nilanjan
Thorleifsson, Gudmar
Sulem, Patrick
Liu, Geoffrey
Kaaks, Rudolf
Henrion, Marc
Kinnersley, Ben
Vallée, Maxime
LeCalvez-Kelm, Florence
Stevens, Victoria L.
Gapstur, Susan M.
Chen, Wei V.
Zaridze, David
Szeszenia-Dabrowska, Neonilia
Lissowska, Jolanta
Rudnai, Peter
Fabianova, Eleonora
Mates, Dana
Bencko, Vladimir
Foretova, Lenka
Janout, Vladimir
Krokan, Hans E.
Gabrielsen, Maiken Elvestad
Skorpen, Frank
Vatten, Lars
Suggested citation
Wang, Yufei; McKay, James D.; Rafnar, Thorunn; Wang, Zhaoming; Timofeeva, Maria N.; Broderick, Peter; ... Vatten, Lars. (2014) . Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer. Nature Genetics, 2014, num. 46, p. 736-741. https://doi.org/10.1038/ng.3002.
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Abstract
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.
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http://hdl.handle.net/10459.1/68025
DOI
https://doi.org/10.1038/ng.3002
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Nature Genetics, 2014, num. 46, p. 736-741
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