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

Xuemei Ji; Semanti Mukherjee; Maria Teresa Landi; Yohan Bosse; Philippe Joubert; Dakai Zhu; Ivan Gorlov; Xiangjun Xiao; Younghun Han; Olga Gorlova; Rayjean J. Hung; Yonathan Brhane; Robert Carreras-Torres; David C. Christiani; Neil Caporaso; Mattias Johansson; Geoffrey Liu; Stig E. Bojesen; Loic Le Marchand; Demetrios Albanes; Heike Bickeböller; Melinda C. Aldrich; William S. Bush; Adonina Tardon; Gad Rennert; Chu Chen; Jinyoung Byun; Konstantin H. Dragnev; John K. Field; Lambertus Fa Kiemeney; Philip Lazarus; Shan Zienolddiny; Stephen Lam; Matthew B. Schabath; Angeline S. Andrew; Pier A. Bertazzi; Angela C. Pesatori; Nancy Diao; Li Su; Lei Song; Ruyang Zhang; Natasha Leighl; Jakob S. Johansen; Anders Mellemgaard; Walid Saliba; Christopher Haiman; Lynne Wilkens; Ana Fernandez-Somoano; Guillermo Fernandez-Tardon; Erik H.F.M.van der Heijden; Jin Hee Kim; Michael P.A. Davies; Michael W. Marcus; Hans Brunnström; Jonas Manjer; Olle Melander; David C. Muller; Kim Overvad; Antonia Trichopoulou; Rosario Tumino; Gary E. Goodman; Angela Cox; Fiona Taylor; Penella Woll; Erich Wichmann; Thomas Muley; Angela Risch; Albert Rosenberger; Kjell Grankvist; Mikael Johansson; Frances Shepherd; Ming Sound Tsao; Susanne M. Arnold; Eric B. Haura; Ciprian Bolca; Ivana Holcatova; Vladimir Janout; Milica Kontic; Jolanta Lissowska; Anush Mukeria; Simona Ognjanovic; Tadeusz M. Orlowski; Ghislaine Scelo; Beata Swiatkowska; David Zaridze; Per Bakke; Vidar Skaug; Lesley M. Butler; Kenneth Offit; Preethi Srinivasan; Chaitanya Bandlamudi; Matthew D. Hellmann; David B. Solit; Mark E. Robson; Charles M. Rudin; Zsofia K. Stadler; Barry S. Taylor; Michael F. Berger; Richard Houlston; John McLaughlin; Victoria Stevens; David C. Nickle; Ma’en Obeidat; Wim Timens; María Soler Artigas; Sanjay Shete; Hermann Brenner; Stephen Chanock; Paul Brennan; James D. McKay; Christopher I. Amos

doi:10.1038/s41467-020-15905-6

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

Xuemei Ji^*, Semanti Mukherjee, Maria Teresa Landi, Yohan Bosse, Philippe Joubert, Dakai Zhu, Ivan Gorlov, Xiangjun Xiao, Younghun Han, Olga Gorlova, Rayjean J. Hung, Yonathan Brhane, Robert Carreras-Torres, David C. Christiani, Neil Caporaso, Mattias Johansson, Geoffrey Liu, Stig E. Bojesen, Loic Le Marchand, Demetrios AlbanesHeike Bickeböller, Melinda C. Aldrich, William S. Bush, Adonina Tardon, Gad Rennert, Chu Chen, Jinyoung Byun, Konstantin H. Dragnev, John K. Field, Lambertus Fa Kiemeney, Philip Lazarus, Shan Zienolddiny, Stephen Lam, Matthew B. Schabath, Angeline S. Andrew, Pier A. Bertazzi, Angela C. Pesatori, Nancy Diao, Li Su, Lei Song, Ruyang Zhang, Natasha Leighl, Jakob S. Johansen, Anders Mellemgaard, Walid Saliba, Christopher Haiman, Lynne Wilkens, Ana Fernandez-Somoano, Guillermo Fernandez-Tardon, Erik H.F.M.van der Heijden, Jin Hee Kim, Michael P.A. Davies, Michael W. Marcus, Hans Brunnström, Jonas Manjer, Olle Melander, David C. Muller, Kim Overvad, Antonia Trichopoulou, Rosario Tumino, Gary E. Goodman, Angela Cox, Fiona Taylor, Penella Woll, Erich Wichmann, Thomas Muley, Angela Risch, Albert Rosenberger, Kjell Grankvist, Mikael Johansson, Frances Shepherd, Ming Sound Tsao, Susanne M. Arnold, Eric B. Haura, Ciprian Bolca, Ivana Holcatova, Vladimir Janout, Milica Kontic, Jolanta Lissowska, Anush Mukeria, Simona Ognjanovic, Tadeusz M. Orlowski, Ghislaine Scelo, Beata Swiatkowska, David Zaridze, Per Bakke, Vidar Skaug, Lesley M. Butler, Kenneth Offit, Preethi Srinivasan, Chaitanya Bandlamudi, Matthew D. Hellmann, David B. Solit, Mark E. Robson, Charles M. Rudin, Zsofia K. Stadler, Barry S. Taylor, Michael F. Berger, Richard Houlston, John McLaughlin, Victoria Stevens, David C. Nickle, Ma’en Obeidat, Wim Timens, María Soler Artigas, Sanjay Shete, Hermann Brenner, Stephen Chanock, Paul Brennan, James D. McKay, Christopher I. Amos

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

32 Citationer (Scopus)

24 Downloads (Pure)

Abstract

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.

Originalsprog	Engelsk
Artikelnummer	2220
Tidsskrift	Nature Communications
Vol/bind	11
Udgave nummer	1
ISSN	2041-1723
DOI	https://doi.org/10.1038/s41467-020-15905-6
Status	Udgivet - 2020

Adgang til dokumentet

10.1038/s41467-020-15905-6Licens: CC BY

Protein-altering germline mutations implicate novel genes related to lung cancer developmentForlagets udgivne version, 2,34 MBLicens: CC BY

Citationsformater

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., ... Amos, C. I. (2020). Protein-altering germline mutations implicate novel genes related to lung cancer development. Nature Communications, 11(1), Artikel 2220. https://doi.org/10.1038/s41467-020-15905-6

Ji, X, Mukherjee, S, Landi, MT, Bosse, Y, Joubert, P, Zhu, D, Gorlov, I, Xiao, X, Han, Y, Gorlova, O, Hung, RJ, Brhane, Y, Carreras-Torres, R, Christiani, DC, Caporaso, N, Johansson, M, Liu, G, Bojesen, SE, Le Marchand, L, Albanes, D, Bickeböller, H, Aldrich, MC, Bush, WS, Tardon, A, Rennert, G, Chen, C, Byun, J, Dragnev, KH, Field, JK, Kiemeney, LF, Lazarus, P, Zienolddiny, S, Lam, S, Schabath, MB, Andrew, AS, Bertazzi, PA, Pesatori, AC, Diao, N, Su, L, Song, L, Zhang, R, Leighl, N, Johansen, JS, Mellemgaard, A, Saliba, W, Haiman, C, Wilkens, L, Fernandez-Somoano, A, Fernandez-Tardon, G, Heijden, EHFMVD, Kim, JH, Davies, MPA, Marcus, MW, Brunnström, H, Manjer, J, Melander, O, Muller, DC, Overvad, K, Trichopoulou, A, Tumino, R, Goodman, GE, Cox, A, Taylor, F, Woll, P, Wichmann, E, Muley, T, Risch, A, Rosenberger, A, Grankvist, K, Johansson, M, Shepherd, F, Tsao, MS, Arnold, SM, Haura, EB, Bolca, C, Holcatova, I, Janout, V, Kontic, M, Lissowska, J, Mukeria, A, Ognjanovic, S, Orlowski, TM, Scelo, G, Swiatkowska, B, Zaridze, D, Bakke, P, Skaug, V, Butler, LM, Offit, K, Srinivasan, P, Bandlamudi, C, Hellmann, MD, Solit, DB, Robson, ME, Rudin, CM, Stadler, ZK, Taylor, BS, Berger, MF, Houlston, R, McLaughlin, J, Stevens, V, Nickle, DC, Obeidat, M, Timens, W, Artigas, MS, Shete, S, Brenner, H, Chanock, S, Brennan, P, McKay, JD & Amos, CI 2020, 'Protein-altering germline mutations implicate novel genes related to lung cancer development', Nature Communications, bind 11, nr. 1, 2220. https://doi.org/10.1038/s41467-020-15905-6

@article{634346e45dcb4714b8d37a16a737bf8a,

title = "Protein-altering germline mutations implicate novel genes related to lung cancer development",

abstract = "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.",

author = "Xuemei Ji and Semanti Mukherjee and Landi, {Maria Teresa} and Yohan Bosse and Philippe Joubert and Dakai Zhu and Ivan Gorlov and Xiangjun Xiao and Younghun Han and Olga Gorlova and Hung, {Rayjean J.} and Yonathan Brhane and Robert Carreras-Torres and Christiani, {David C.} and Neil Caporaso and Mattias Johansson and Geoffrey Liu and Bojesen, {Stig E.} and {Le Marchand}, Loic and Demetrios Albanes and Heike Bickeb{\"o}ller and Aldrich, {Melinda C.} and Bush, {William S.} and Adonina Tardon and Gad Rennert and Chu Chen and Jinyoung Byun and Dragnev, {Konstantin H.} and Field, {John K.} and Kiemeney, {Lambertus Fa} and Philip Lazarus and Shan Zienolddiny and Stephen Lam and Schabath, {Matthew B.} and Andrew, {Angeline S.} and Bertazzi, {Pier A.} and Pesatori, {Angela C.} and Nancy Diao and Li Su and Lei Song and Ruyang Zhang and Natasha Leighl and Johansen, {Jakob S.} and Anders Mellemgaard and Walid Saliba and Christopher Haiman and Lynne Wilkens and Ana Fernandez-Somoano and Guillermo Fernandez-Tardon and Heijden, {Erik H.F.M.van der} and Kim, {Jin Hee} and Davies, {Michael P.A.} and Marcus, {Michael W.} and Hans Brunnstr{\"o}m and Jonas Manjer and Olle Melander and Muller, {David C.} and Kim Overvad and Antonia Trichopoulou and Rosario Tumino and Goodman, {Gary E.} and Angela Cox and Fiona Taylor and Penella Woll and Erich Wichmann and Thomas Muley and Angela Risch and Albert Rosenberger and Kjell Grankvist and Mikael Johansson and Frances Shepherd and Tsao, {Ming Sound} and Arnold, {Susanne M.} and Haura, {Eric B.} and Ciprian Bolca and Ivana Holcatova and Vladimir Janout and Milica Kontic and Jolanta Lissowska and Anush Mukeria and Simona Ognjanovic and Orlowski, {Tadeusz M.} and Ghislaine Scelo and Beata Swiatkowska and David Zaridze and Per Bakke and Vidar Skaug and Butler, {Lesley M.} and Kenneth Offit and Preethi Srinivasan and Chaitanya Bandlamudi and Hellmann, {Matthew D.} and Solit, {David B.} and Robson, {Mark E.} and Rudin, {Charles M.} and Stadler, {Zsofia K.} and Taylor, {Barry S.} and Berger, {Michael F.} and Richard Houlston and John McLaughlin and Victoria Stevens and Nickle, {David C.} and Ma{\textquoteright}en Obeidat and Wim Timens and Artigas, {Mar{\'i}a Soler} and Sanjay Shete and Hermann Brenner and Stephen Chanock and Paul Brennan and McKay, {James D.} and Amos, {Christopher I.}",

year = "2020",

doi = "10.1038/s41467-020-15905-6",

language = "English",

volume = "11",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "nature publishing group",

number = "1",

}

TY - JOUR

T1 - Protein-altering germline mutations implicate novel genes related to lung cancer development

AU - Ji, Xuemei

AU - Mukherjee, Semanti

AU - Landi, Maria Teresa

AU - Bosse, Yohan

AU - Joubert, Philippe

AU - Zhu, Dakai

AU - Gorlov, Ivan

AU - Xiao, Xiangjun

AU - Han, Younghun

AU - Gorlova, Olga

AU - Hung, Rayjean J.

AU - Brhane, Yonathan

AU - Carreras-Torres, Robert

AU - Christiani, David C.

AU - Caporaso, Neil

AU - Johansson, Mattias

AU - Liu, Geoffrey

AU - Bojesen, Stig E.

AU - Le Marchand, Loic

AU - Albanes, Demetrios

AU - Bickeböller, Heike

AU - Aldrich, Melinda C.

AU - Bush, William S.

AU - Tardon, Adonina

AU - Rennert, Gad

AU - Chen, Chu

AU - Byun, Jinyoung

AU - Dragnev, Konstantin H.

AU - Field, John K.

AU - Kiemeney, Lambertus Fa

AU - Lazarus, Philip

AU - Zienolddiny, Shan

AU - Lam, Stephen

AU - Schabath, Matthew B.

AU - Andrew, Angeline S.

AU - Bertazzi, Pier A.

AU - Pesatori, Angela C.

AU - Diao, Nancy

AU - Su, Li

AU - Song, Lei

AU - Zhang, Ruyang

AU - Leighl, Natasha

AU - Johansen, Jakob S.

AU - Mellemgaard, Anders

AU - Saliba, Walid

AU - Haiman, Christopher

AU - Wilkens, Lynne

AU - Fernandez-Somoano, Ana

AU - Fernandez-Tardon, Guillermo

AU - Heijden, Erik H.F.M.van der

AU - Kim, Jin Hee

AU - Davies, Michael P.A.

AU - Marcus, Michael W.

AU - Brunnström, Hans

AU - Manjer, Jonas

AU - Melander, Olle

AU - Muller, David C.

AU - Overvad, Kim

AU - Trichopoulou, Antonia

AU - Tumino, Rosario

AU - Goodman, Gary E.

AU - Cox, Angela

AU - Taylor, Fiona

AU - Woll, Penella

AU - Wichmann, Erich

AU - Muley, Thomas

AU - Risch, Angela

AU - Rosenberger, Albert

AU - Grankvist, Kjell

AU - Johansson, Mikael

AU - Shepherd, Frances

AU - Tsao, Ming Sound

AU - Arnold, Susanne M.

AU - Haura, Eric B.

AU - Bolca, Ciprian

AU - Holcatova, Ivana

AU - Janout, Vladimir

AU - Kontic, Milica

AU - Lissowska, Jolanta

AU - Mukeria, Anush

AU - Ognjanovic, Simona

AU - Orlowski, Tadeusz M.

AU - Scelo, Ghislaine

AU - Swiatkowska, Beata

AU - Zaridze, David

AU - Bakke, Per

AU - Skaug, Vidar

AU - Butler, Lesley M.

AU - Offit, Kenneth

AU - Srinivasan, Preethi

AU - Bandlamudi, Chaitanya

AU - Hellmann, Matthew D.

AU - Solit, David B.

AU - Robson, Mark E.

AU - Rudin, Charles M.

AU - Stadler, Zsofia K.

AU - Taylor, Barry S.

AU - Berger, Michael F.

AU - Houlston, Richard

AU - McLaughlin, John

AU - Stevens, Victoria

AU - Nickle, David C.

AU - Obeidat, Ma’en

AU - Timens, Wim

AU - Artigas, María Soler

AU - Shete, Sanjay

AU - Brenner, Hermann

AU - Chanock, Stephen

AU - Brennan, Paul

AU - McKay, James D.

AU - Amos, Christopher I.

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-020-15905-6

DO - 10.1038/s41467-020-15905-6

M3 - Journal article

C2 - 32393777

AN - SCOPUS:85084474621

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2220

ER -