Protein-altering germline mutations implicate novel genes related to lung cancer development

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.; Johansson, M.; Shepherd, F.; Tsao, M.-.; 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.

doi:10.1038/s41467-020-15905-6

IRIS Institutional Research Information System - AIR Archivio Istituzionale della Ricerca

IRIS è il sistema di gestione integrata dei dati della ricerca (persone, progetti, pubblicazioni, attività) adottato dall'Università degli Studi di Milano.

AIR nasce in UNIMI nel 2006 con lo scopo di raccogliere, documentare e conservare le informazioni sulla produzione scientifica dell'Università degli Studi di Milano e costituisce di fatto l'Anagrafe della ricerca dell'Ateneo.

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.

Protein-altering germline mutations implicate novel genes related to lung cancer development / 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-Torres, D.C. Christiani, N. Caporaso, M. Johansson, G. Liu, S.E. Bojesen, L. Le Marchand, D. Albanes, 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. Lazarus, 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. Wilkens, A. Fernandez-Somoano, G. Fernandez-Tardon, E.H.F.M. Heijden, J.H. Kim, M.P.A. Davies, M.W. Marcus, 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, M. Johansson, 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, V. Stevens, D.C. Nickle, M. Obeidat, W. Timens, M.S. Artigas, S. Shete, H. Brenner, S. Chanock, P. Brennan, J.D. McKay, C.I. Amos. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 11:1(2020 Dec 01).

Titolo:	Protein-altering germline mutations implicate novel genes related to lung cancer development
Autori:	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, PIETRO ALBERTO PESATORI, ANGELA CECILIA 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. Johansson M. 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. (Corresponding) mostra contributor esterni nascondi contributor esterni
Parole Chiave:	Adenocarcinoma; Aged; Alleles; Ataxia Telangiectasia Mutated Proteins; Databases, Genetic; European Continental Ancestry Group; Female; Genetic Predisposition to Disease; Genotyping Techniques; Germ-Line Mutation; Heterozygote; Humans; Jews; Lung Neoplasms; Male; Middle Aged; Mutation, Missense; Odds Ratio; Oligonucleotide Array Sequence Analysis; Pedigree; RNA-Seq; Risk Factors
Settore Scientifico Disciplinare:	Settore MED/44 - Medicina del Lavoro
Data di pubblicazione:	1-dic-2020
Rivista:	NATURE COMMUNICATIONS
Tipologia:	Article (author)
Data ahead of print / Data di stampa:	11-mag-2020
Digital Object Identifier (DOI):	http://dx.doi.org/10.1038/s41467-020-15905-6
Appare nelle tipologie:	01 - Articolo su periodico

File in questo prodotto:

File	Descrizione	Tipologia	Licenza
41467_2020_Article_15905.pdf		Publisher's version/PDF		Open Access Visualizza/Apri

Utilizza questo identificativo per citare o creare un link a questo documento:
http://hdl.handle.net/2434/801623

Citazioni

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.