Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated with lung cancer risk, with P values less than 0.05 and FDR less than 0.1. Functional annotation of eQTL analysis results showed that the neuroactive ligand receptor interaction pathway and gated channel activity were involved in lung cancer risk. These pathways provide important insights for the etiology of lung cancer.

Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk / X. Ji, Y. Bossé, M.T. Landi, J. Gui, X. Xiao, D. Qian, P. Joubert, M. Lamontagne, Y. Li, I. Gorlov, M. de Biasi, Y. Han, O. Gorlova, R.J. Hung, X. Wu, J. Mckay, X. Zong, R. Carreras-Torres, D.C. Christiani, N. Caporaso, M. Johansson, G. Liu, S.E. Bojesen, L. Le Marchand, D. Albanes, H. Bickeböller, M.C. Aldrich, W.S. Bush, A. Tardon, G. Rennert, C. Chen, M.D. Teare, J.K. Field, L.A. Kiemeney, P. Lazarus, A. Haugen, S. Lam, M.B. Schabath, A.S. Andrew, H. Shen, Y. Hong, J. Yuan, P.A. Bertazzi, A.C. Pesatori, Y. Ye, N. Diao, L. Su, R. Zhang, Y. Brhane, N. Leighl, J.S. Johansen, A. Mellemgaard, W. Saliba, C. Haiman, L. Wilkens, A. Fernandez-Somoano, G. Fernandez-Tardon, E.H.F.M. van der Heijden, J.H. Kim, J. Dai, Z. Hu, M.P.A. Davies, M.W. Marcus, H. Brunnström, J. Manjer, O. Melander, D.C. Muller, K. Overvad, A. Trichopoulou, R. Tumino, J. Doherty, G.E. Goodman, A. Cox, F. Taylor, P. Woll, I. Brüske, J. Manz, 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, S. Zienolddiny, E.J. Duell, L.M. Butler, W. Koh, Y. Gao, R. Houlston, J. Mclaughlin, V. Stevens, D.C. Nickle, M. Obeidat, W. Timens, B. Zhu, L. Song, M.S. Artigas, M.D. Tobin, L.V. Wain, F. Gu, J. Byun, A. Kamal, D. Zhu, R.F. Tyndale, W. Wei, S. Chanock, P. Brennan, C.I. Amos. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 9:1(2018 Aug 13). [10.1038/s41467-018-05074-y]

Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk

A.C. Pesatori;
2018-08-13

Abstract

Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated with lung cancer risk, with P values less than 0.05 and FDR less than 0.1. Functional annotation of eQTL analysis results showed that the neuroactive ligand receptor interaction pathway and gated channel activity were involved in lung cancer risk. These pathways provide important insights for the etiology of lung cancer.
Adolescent; Adult; Aged; Child; Child, Preschool; Chromosomes, Human, Pair 15; Cohort Studies; Female; Gene Ontology; Gene Regulatory Networks; Humans; Infant; Infant, Newborn; Lung Neoplasms; Male; Middle Aged; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Reproducibility of Results; Risk Factors; Smoking; Young Adult; Genetic Predisposition to Disease; Chemistry (all); Biochemistry, Genetics and Molecular Biology (all); Physics and Astronomy (all)
Settore MED/44 - Medicina del Lavoro
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/615772
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