Protein-altering germline mutations implicate novel genes related to lung cancer development. Other Scholarly Work

Ji, Xuemei, Mukherjee, Semanti, Landi, Maria Teresa et al. (2020). Protein-altering germline mutations implicate novel genes related to lung cancer development. . 11(1), 2220. 10.1038/s41467-020-15905-6

cited authors

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

fiu authors

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.

publication date

  • May 11, 2020

keywords

  • Adenocarcinoma
  • Aged
  • Alleles
  • Ataxia Telangiectasia Mutated Proteins
  • Databases, Genetic
  • 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
  • Whites

Digital Object Identifier (DOI)

Medium

  • Electronic

start page

  • 2220

volume

  • 11

issue

  • 1