دورية أكاديمية
Protein-altering germline mutations implicate novel genes related to lung cancer development
| العنوان: | Protein-altering germline mutations implicate novel genes related to lung cancer development |
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| المؤلفون: | Ji X., Mukherjee S., Landi M. T., Bosse Y., Joubert P., Zhu D., Gorlov I., Xiao X., Han Y., Gorlova O., Hung R. J., Brhane Y., Carreras-Torres R., Christiani D. C., Caporaso N., Johansson M., Liu G., Bojesen S. E., Le Marchand L., Albanes D., Bickeboller H., Aldrich M. C., Bush W. S., Tardon A., Rennert G., Chen C., Byun J., Dragnev K. H., Field J. K., Kiemeney L. F., Lazarus P., Zienolddiny S., Lam S., Schabath M. B., Andrew A. S., Bertazzi P. A., Pesatori A. C., Diao N., Su L., Song L., Zhang R., Leighl N., Johansen J. S., Mellemgaard A., Saliba W., Haiman C., Wilkens L., Fernandez-Somoano A., Fernandez-Tardon G., Heijden E. H. F. M., Kim J. H., Davies M. P. A., Marcus M. W., Brunnstrom H., Manjer J., Melander O., Muller D. C., Overvad K., Trichopoulou A., Tumino R., Goodman G. E., Cox A., Taylor F., Woll P., Wichmann E., Muley T., Risch A., Rosenberger A., Grankvist K., Shepherd F., Tsao M. -S., Arnold S. M., Haura E. B., Bolca C., Holcatova I., Janout V., Kontic M., Lissowska J., Mukeria A., Ognjanovic S., Orlowski T. M., Scelo G., Swiatkowska B., Zaridze D., Bakke P., Skaug V., Butler L. M., Offit K., Srinivasan P., Bandlamudi C., Hellmann M. D., Solit D. B., Robson M. E., Rudin C. M., Stadler Z. K., Taylor B. S., Berger M. F., Houlston R., McLaughlin J., Stevens V., Nickle D. C., Obeidat M., Timens W., Artigas M. S., Shete S., Brenner H., Chanock S., Brennan P., McKay J. D., Amos C. I. |
| المساهمون: | X. Ji, S. Mukherjee, M.T. Landi, Y. Bosse, P. Joubert, D. Zhu, I. Gorlov, X. Xiao, Y. Han, O. Gorlova, R.J. Hung, Y. Brhane, R. Carreras-Torre, D.C. Christiani, N. Caporaso, M. Johansson, G. Liu, S.E. Bojesen, L. Le Marchand, D. Albane, H. Bickeboller, M.C. Aldrich, W.S. Bush, A. Tardon, G. Rennert, C. Chen, J. Byun, K.H. Dragnev, J.K. Field, L.F. Kiemeney, P. Lazaru, S. Zienolddiny, S. Lam, M.B. Schabath, A.S. Andrew, P.A. Bertazzi, A.C. Pesatori, N. Diao, L. Su, L. Song, R. Zhang, N. Leighl, J.S. Johansen, A. Mellemgaard, W. Saliba, C. Haiman, L. Wilken, A. Fernandez-Somoano, G. Fernandez-Tardon, E.H.F.M. Heijden, J.H. Kim, M.P.A. Davie, M.W. Marcu, H. Brunnstrom, J. Manjer, O. Melander, D.C. Muller, K. Overvad, A. Trichopoulou, R. Tumino, G.E. Goodman, A. Cox, F. Taylor, P. Woll, E. Wichmann, T. Muley, A. Risch, A. Rosenberger, K. Grankvist, F. Shepherd, M.-. Tsao, S.M. Arnold, E.B. Haura, C. Bolca, I. Holcatova, V. Janout, M. Kontic, J. Lissowska, A. Mukeria, S. Ognjanovic, T.M. Orlowski, G. Scelo, B. Swiatkowska, D. Zaridze, P. Bakke, V. Skaug, L.M. Butler, K. Offit, P. Srinivasan, C. Bandlamudi, M.D. Hellmann, D.B. Solit, M.E. Robson, C.M. Rudin, Z.K. Stadler, B.S. Taylor, M.F. Berger, R. Houlston, J. Mclaughlin |
| بيانات النشر: | Nature Research |
| سنة النشر: | 2020 |
| المجموعة: | The University of Milan: Archivio Istituzionale della Ricerca (AIR) |
| مصطلحات موضوعية: | Adenocarcinoma, Aged, Allele, Ataxia Telangiectasia Mutated Protein, Databases, Genetic, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genotyping Technique, Germ-Line Mutation, Heterozygote, Human, Jew, Lung Neoplasm, Male, Middle Aged, Mutation, Missense, Odds Ratio, Oligonucleotide Array Sequence Analysi, Pedigree, RNA-Seq, Risk Factors, Settore MED/44 - Medicina del Lavoro |
| الوصف: | Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio = 8.82, P = 1.18 × 10−15) and replication (adjusted OR = 2.93, P = 2.22 × 10−3) that is more pronounced in females (adjusted OR = 6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is more frequent (4%) among Ashkenazi Jewish populations. We also observe an association in discovery (adjusted OR = 2.61, P = 7.98 × 10−22) and replication datasets (adjusted OR = 1.55, P = 0.06) with a loss-of-function mutation, Q4X (rs150665432) of an uncharacterized gene, KIAA0930. Our findings implicate germline genetic variants in ATM with lung cancer susceptibility and suggest KIAA0930 as a novel candidate gene for lung cancer risk. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/32393777; info:eu-repo/semantics/altIdentifier/wos/WOS:000558695400001; volume:11; issue:1; numberofpages:14; journal:NATURE COMMUNICATIONS; http://hdl.handle.net/2434/801623Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85084474621 |
| DOI: | 10.1038/s41467-020-15905-6 |
| الإتاحة: | https://doi.org/10.1038/s41467-020-15905-6Test http://hdl.handle.net/2434/801623Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.EEEF0FFE |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-020-15905-6 |
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