Lung Cancer Risk in Never-Smokers of European Descent is Associated With Genetic Variation in the 5p15.33 TERT-CLPTM1Ll Region
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Lung Cancer Risk in Never-Smokers of European Descent is Associated With Genetic Variation in the 5p15.33 TERT-CLPTM1Ll Region. / Hung, Rayjean J.; Spitz, Margaret R.; Houlston, Richard S.; Schwartz, Ann G.; Field, John K.; Ying, Jun; Li, Yafang; Han, Younghun; Ji, Xuemei; Chen, Wei; Wu, Xifeng; Gorlov, Ivan P.; Na, Jie; de Andrade, Mariza; Liu, Geoffrey; Brhane, Yonathan; Diao, Nancy; Wenzlaff, Angela; Davies, Michael P.A.; Liloglou, Triantafillos; Timofeeva, Maria; Muley, Thomas; Rennert, Hedy; Saliba, Walid; Ryan, Bríd M.; Bowman, Elise; Barros-Dios, Juan Miguel; Pérez-Ríos, Mónica; Morgenstern, Hal; Zienolddiny, Shanbeh; Skaug, Vidar; Ugolini, Donatella; Bonassi, Stefano; van der Heijden, Erik H.F.M.; Tardon, Adonina; Bojesen, Stig E.; Landi, Maria Teresa; Johansson, Mattias; Bickeböller, Heike; Arnold, Susanne; Le Marchand, Loic; Melander, Olle; Andrew, Angeline; Grankvist, Kjell; Caporaso, Neil; Teare, M. Dawn; Schabath, Matthew B.; Aldrich, Melinda C.; Kiemeney, Lambertus A.; Wichmann, H. Erich; Lazarus, Philip; Mayordomo, Jose; Neri, Monica; Haugen, Aage; Zhang, Zuo Feng; Ruano-Raviña, Alberto; Brenner, Hermann; Harris, Curtis C.; Orlow, Irene; Rennert, Gadi; Risch, Angela; Brennan, Paul; Christiani, David C.; Amos, Christopher I.; Yang, Ping; Gorlova, Olga Y.
I: Journal of Thoracic Oncology, Bind 14, Nr. 8, 08.2019, s. 1360-1369.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Lung Cancer Risk in Never-Smokers of European Descent is Associated With Genetic Variation in the 5p15.33 TERT-CLPTM1Ll Region
AU - Hung, Rayjean J.
AU - Spitz, Margaret R.
AU - Houlston, Richard S.
AU - Schwartz, Ann G.
AU - Field, John K.
AU - Ying, Jun
AU - Li, Yafang
AU - Han, Younghun
AU - Ji, Xuemei
AU - Chen, Wei
AU - Wu, Xifeng
AU - Gorlov, Ivan P.
AU - Na, Jie
AU - de Andrade, Mariza
AU - Liu, Geoffrey
AU - Brhane, Yonathan
AU - Diao, Nancy
AU - Wenzlaff, Angela
AU - Davies, Michael P.A.
AU - Liloglou, Triantafillos
AU - Timofeeva, Maria
AU - Muley, Thomas
AU - Rennert, Hedy
AU - Saliba, Walid
AU - Ryan, Bríd M.
AU - Bowman, Elise
AU - Barros-Dios, Juan Miguel
AU - Pérez-Ríos, Mónica
AU - Morgenstern, Hal
AU - Zienolddiny, Shanbeh
AU - Skaug, Vidar
AU - Ugolini, Donatella
AU - Bonassi, Stefano
AU - van der Heijden, Erik H.F.M.
AU - Tardon, Adonina
AU - Bojesen, Stig E.
AU - Landi, Maria Teresa
AU - Johansson, Mattias
AU - Bickeböller, Heike
AU - Arnold, Susanne
AU - Le Marchand, Loic
AU - Melander, Olle
AU - Andrew, Angeline
AU - Grankvist, Kjell
AU - Caporaso, Neil
AU - Teare, M. Dawn
AU - Schabath, Matthew B.
AU - Aldrich, Melinda C.
AU - Kiemeney, Lambertus A.
AU - Wichmann, H. Erich
AU - Lazarus, Philip
AU - Mayordomo, Jose
AU - Neri, Monica
AU - Haugen, Aage
AU - Zhang, Zuo Feng
AU - Ruano-Raviña, Alberto
AU - Brenner, Hermann
AU - Harris, Curtis C.
AU - Orlow, Irene
AU - Rennert, Gadi
AU - Risch, Angela
AU - Brennan, Paul
AU - Christiani, David C.
AU - Amos, Christopher I.
AU - Yang, Ping
AU - Gorlova, Olga Y.
PY - 2019/8
Y1 - 2019/8
N2 - Introduction: Inherited susceptibility to lung cancer risk in never-smokers is poorly understood. The major reason for this gap in knowledge is that this disease is relatively uncommon (except in Asians), making it difficult to assemble an adequate study sample. In this study we conducted a genome-wide association study on the largest, to date, set of European-descent never-smokers with lung cancer. Methods: We conducted a two-phase (discovery and replication) genome-wide association study in never-smokers of European descent. We further augmented the sample by performing a meta-analysis with never-smokers from the recent OncoArray study, which resulted in a total of 3636 cases and 6295 controls. We also compare our findings with those in smokers with lung cancer. Results: We detected three genome-wide statistically significant single nucleotide polymorphisms rs31490 (odds ratio [OR]: 0.769, 95% confidence interval [CI]: 0.722–0.820; p value 5.31 × 10-16), rs380286 (OR: 0.770, 95% CI: 0.723–0.820; p value 4.32 × 10-16), and rs4975616 (OR: 0.778, 95% CI: 0.730–0.829; p value 1.04 × 10-14). All three mapped to Chromosome 5 CLPTM1L-TERT region, previously shown to be associated with lung cancer risk in smokers and in never-smoker Asian women, and risk of other cancers including breast, ovarian, colorectal, and prostate. Conclusions: We found that genetic susceptibility to lung cancer in never-smokers is associated to genetic variants with pan-cancer risk effects. The comparison with smokers shows that top variants previously shown to be associated with lung cancer risk only confer risk in the presence of tobacco exposure, underscoring the importance of gene-environment interactions in the etiology of this disease.
AB - Introduction: Inherited susceptibility to lung cancer risk in never-smokers is poorly understood. The major reason for this gap in knowledge is that this disease is relatively uncommon (except in Asians), making it difficult to assemble an adequate study sample. In this study we conducted a genome-wide association study on the largest, to date, set of European-descent never-smokers with lung cancer. Methods: We conducted a two-phase (discovery and replication) genome-wide association study in never-smokers of European descent. We further augmented the sample by performing a meta-analysis with never-smokers from the recent OncoArray study, which resulted in a total of 3636 cases and 6295 controls. We also compare our findings with those in smokers with lung cancer. Results: We detected three genome-wide statistically significant single nucleotide polymorphisms rs31490 (odds ratio [OR]: 0.769, 95% confidence interval [CI]: 0.722–0.820; p value 5.31 × 10-16), rs380286 (OR: 0.770, 95% CI: 0.723–0.820; p value 4.32 × 10-16), and rs4975616 (OR: 0.778, 95% CI: 0.730–0.829; p value 1.04 × 10-14). All three mapped to Chromosome 5 CLPTM1L-TERT region, previously shown to be associated with lung cancer risk in smokers and in never-smoker Asian women, and risk of other cancers including breast, ovarian, colorectal, and prostate. Conclusions: We found that genetic susceptibility to lung cancer in never-smokers is associated to genetic variants with pan-cancer risk effects. The comparison with smokers shows that top variants previously shown to be associated with lung cancer risk only confer risk in the presence of tobacco exposure, underscoring the importance of gene-environment interactions in the etiology of this disease.
KW - Genetic susceptibility
KW - Genome-wide association study
KW - Lung cancer
KW - Never smokers
U2 - 10.1016/j.jtho.2019.04.008
DO - 10.1016/j.jtho.2019.04.008
M3 - Journal article
C2 - 31009812
AN - SCOPUS:85066990163
VL - 14
SP - 1360
EP - 1369
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
SN - 1556-0864
IS - 8
ER -
ID: 241943117