Lung cancer risk in never-smokers of European descent is associated with genetic variation in the 5(p)15.33 TERT-CLPTM1Ll region.

التفاصيل البيبلوغرافية
العنوان:	Lung cancer risk in never-smokers of European descent is associated with genetic variation in the 5(p)15.33 TERT-CLPTM1Ll region.
المؤلفون:	Hung, R.J., Spitz, M.R., Houlston, R.S., Schwartz, A.G., Field, J.K., Ying, J., Li, Y., Han, Y., Ji, X., Chen, W., Wu, X., Gorlov, I.P., Na, J., de Andrade, M., Liu, G., Brhane, Y., Diao, N., Wenzlaff, A., Davies, M.P.A., Liloglou, T., Timofeeva, M., Muley, T., Rennert, H., Saliba, W., Ryan, B.M., Bowman, E., Barros-Dios, J.M., Pérez-Ríos, M., Morgenstern, H., Zienolddiny, S., Skaug, V., Ugolini, D., Bonassi, S., van der Heijden, E.H.F.M., Tardón, A., Bojesen, S.E., Landi, M.T., Johansson, M., Bickeböller, H., Arnold, S., Le Marchand, L., Melander, O., Andrew, A., Grankvist, K., Caporaso, N., Teare, M.D., Schabath, M.B., Aldrich, M.C., Kiemeney, L.A., Wichmann, H.-E., Lazarus, P., Mayordomo, J., Neri, M., Haugen, A., Zhang, Z.F., Ruano-Raviña, A., Brenner, H., Harris, C.C., Orlow, I., Rennert, G., Risch, A., Brennan, P., Christiani, D.C., Amos, C.I., Yang, P., Gorlova, O.Y.
المصدر:	J. Thorac. Oncol. 14, 1360-1369 (2019)
بيانات النشر:	Elsevier Science Inc
سنة النشر:	2019
المجموعة:	PuSH - Publikationsserver des Helmholtz Zentrums München
مصطلحات موضوعية:	Lung Cancer, Never Smokers, Genome-wide Association Study, Genetic Susceptibility
الوصف:	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 x 10(-16)), rs380286 (OR: 0.770, 95% CI: 0.723-0.820; p value 4.32 x 10(-16)), and rs4975616 OR: 0.778, 95% CI: 0.730-0.829; p value 1.04 x 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.
نوع الوثيقة:	article in journal/newspaper
وصف الملف:	application/pdf
اللغة:	English
تدمد:	1556-0864 1556-1380
العلاقة:	info:eu-repo/semantics/altIdentifier/pmid/31009812; info:eu-repo/semantics/altIdentifier/wos/WOS:000476595900019; info:eu-repo/semantics/altIdentifier/isbn/1556-0864; info:eu-repo/semantics; https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=55900Test; urn:isbn:1556-0864; urn:issn:1556-0864; urn:issn:1556-1380
DOI:	10.1016/j.jtho.2019.04.008
الإتاحة:	https://doi.org/10.1016/j.jtho.2019.04.008Test https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=55900Test
حقوق:	info:eu-repo/semantics/openAccess
رقم الانضمام:	edsbas.B4272FE
قاعدة البيانات:	BASE

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الوصف
تدمد:	15560864 15561380
DOI:	10.1016/j.jtho.2019.04.008