Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development
The development of cancer is driven by the accumulation of many oncogenesis-related genetic alterationsand tumorigenesis is triggered by complex networks of involved genes rather than independent actions. To explore the epistasis existing among oncogenesis-related genes in lung cancer development, w...
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| creator | Li, Yafang Xiao, Xiangjun Bossé, Yohan Gorlova, Olga Gorlov, Ivan Han, Younghun Byun, Jinyoung Leighl, Natasha Johansen, Jakob S Barnett, Matt Chen, Chu Goodman, Gary Cox, Angela Taylor, Fiona Woll, Penella Wichmann, Erich Manz, Judith Muley, Thomas Risch, Angela Rosenberger, Albert Han, Jiali Siminovitch, Katherine Arnold, Susanne Haura, Eric B Bolca, Ciprian Holcátová, Ivana Janout, Vladimir Kontic, Milica Lissowska, Jolanta Mukeria, Anush Ognjanovic, Simona Orlowski, Tadeusz M Scelo, Ghislaine Swiatkowska, Beata Zaridze, David Bakke, Per S Skaug, Vidar Zienolddiny, Shanbeh Duell, Eric J Butler, Lesley M Houlston, Richard Artigas, Maria Soler Grankvist, Kjell Johansson, Mikael Shepherd, Frances A Marcus, Michael Brunnström, Hans Manjer, Jonas Melander, Olle Muller, David C Overvad, Kim Trichopoulou, Antonia Tumino, Rosaria Liu, Geoffrey Bojesen, Stig Wu, Xifeng Le Marchand, Loic Albanes, Demetrios Bickeböller, Heike Aldrich, Melinda C Bush, William S Tardon, Adonina Rennert, Gad Teare, M. Dawn Field, John K Kiemeney, Lambertus A Lazarus, Philip Haugen, Aage Lam, Stephen Schabath, Matthew B Andrew, Angeline S Bertazzi, Pier Alberto Pesatori, Angela C Christiani, David C Caporaso, Neil Johansson, Mattias McKay, James D Brennan, Paul Hung, Rayjean J Amos, Christopher I |
| description | The development of cancer is driven by the accumulation of many oncogenesis-related genetic alterationsand tumorigenesis is triggered by complex networks of involved genes rather than independent actions. To explore the epistasis existing among oncogenesis-related genes in lung cancer development, we conducted pairwise genetic interaction analyses among 35,031 SNPs from 2027 oncogenesis-related genes. The genotypes from three independent genome-wide association studies including a total of 24,037 lung cancer patients and 20,401 healthy controls with Caucasian ancestry were analyzed in the study. Using a two-stage study design including discovery and replication studies, and stringent Bonferroni correction for multiple statistical analysis, we identified significant genetic interactions between SNPs in RGL1:RAD51B (OR=0.44, p value=3.27x10-11 in overall lung cancer and OR=0.41, p value=9.71x10-11 in non-small cell lung cancer), SYNE1:RNF43 (OR=0.73, p value=1.01x10-12 in adenocarcinoma) and FHIT:TSPAN8 (OR=1.82, p value=7.62x10-11 in squamous cell carcinoma) in our analysis. None of these genes have been identified from previous main effect association studies in lung cancer. Further eQTL gene expression analysis in lung tissues provided information supporting the functional role of the identified epistasis in lung tumorigenesis. Gene set enrichment analysis revealed potential pathways and gene networks underlying molecular mechanisms in overall lung cancer as well as histology subtypes development. Our results provide evidence that genetic interactions between oncogenesis-related genes play an important role in lung tumorigenesis and epistasis analysis, combined with functional annotation, provides a valuable tool for uncovering functional novel susceptibility genes that contribute to lung cancer development by interacting with other modifier genes. |
| format | Article |
| fullrecord | <record><control><sourceid>cristin_3HK</sourceid><recordid>TN_cdi_cristin_nora_11250_2992491</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>11250_2992491</sourcerecordid><originalsourceid>FETCH-cristin_nora_11250_29924913</originalsourceid><addsrcrecordid>eNqNjE0OgjAQhbvQBVHvMB6AhCJIWBt_DuCeTMpIGsuMaSuG29sYDuDq5Xv53lupTDfHItdNU2VqvhJTtAYsR_JoohUGZHRzsAFwFB5A2MiQtNTknhxG6uHH4GkidAlZJnJLiZyY4kf8M6RbcO_0YZANeejTwMlrJI5btX6gC7RbcqP2l_P9dMuNtyFa7lg8dlqXddGVbVtWrT7843wBF6BJCw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development</title><source>NORA - Norwegian Open Research Archives</source><creator>Li, Yafang ; Xiao, Xiangjun ; Bossé, Yohan ; Gorlova, Olga ; Gorlov, Ivan ; Han, Younghun ; Byun, Jinyoung ; Leighl, Natasha ; Johansen, Jakob S ; Barnett, Matt ; Chen, Chu ; Goodman, Gary ; Cox, Angela ; Taylor, Fiona ; Woll, Penella ; Wichmann, Erich ; Manz, Judith ; Muley, Thomas ; Risch, Angela ; Rosenberger, Albert ; Han, Jiali ; Siminovitch, Katherine ; Arnold, Susanne ; Haura, Eric B ; Bolca, Ciprian ; Holcátová, Ivana ; Janout, Vladimir ; Kontic, Milica ; Lissowska, Jolanta ; Mukeria, Anush ; Ognjanovic, Simona ; Orlowski, Tadeusz M ; Scelo, Ghislaine ; Swiatkowska, Beata ; Zaridze, David ; Bakke, Per S ; Skaug, Vidar ; Zienolddiny, Shanbeh ; Duell, Eric J ; Butler, Lesley M ; Houlston, Richard ; Artigas, Maria Soler ; Grankvist, Kjell ; Johansson, Mikael ; Shepherd, Frances A ; Marcus, Michael ; Brunnström, Hans ; Manjer, Jonas ; Melander, Olle ; Muller, David C ; Overvad, Kim ; Trichopoulou, Antonia ; Tumino, Rosaria ; Liu, Geoffrey ; Bojesen, Stig ; Wu, Xifeng ; Le Marchand, Loic ; Albanes, Demetrios ; Bickeböller, Heike ; Aldrich, Melinda C ; Bush, William S ; Tardon, Adonina ; Rennert, Gad ; Teare, M. Dawn ; Field, John K ; Kiemeney, Lambertus A ; Lazarus, Philip ; Haugen, Aage ; Lam, Stephen ; Schabath, Matthew B ; Andrew, Angeline S ; Bertazzi, Pier Alberto ; Pesatori, Angela C ; Christiani, David C ; Caporaso, Neil ; Johansson, Mattias ; McKay, James D ; Brennan, Paul ; Hung, Rayjean J ; Amos, Christopher I</creator><creatorcontrib>Li, Yafang ; Xiao, Xiangjun ; Bossé, Yohan ; Gorlova, Olga ; Gorlov, Ivan ; Han, Younghun ; Byun, Jinyoung ; Leighl, Natasha ; Johansen, Jakob S ; Barnett, Matt ; Chen, Chu ; Goodman, Gary ; Cox, Angela ; Taylor, Fiona ; Woll, Penella ; Wichmann, Erich ; Manz, Judith ; Muley, Thomas ; Risch, Angela ; Rosenberger, Albert ; Han, Jiali ; Siminovitch, Katherine ; Arnold, Susanne ; Haura, Eric B ; Bolca, Ciprian ; Holcátová, Ivana ; Janout, Vladimir ; Kontic, Milica ; Lissowska, Jolanta ; Mukeria, Anush ; Ognjanovic, Simona ; Orlowski, Tadeusz M ; Scelo, Ghislaine ; Swiatkowska, Beata ; Zaridze, David ; Bakke, Per S ; Skaug, Vidar ; Zienolddiny, Shanbeh ; Duell, Eric J ; Butler, Lesley M ; Houlston, Richard ; Artigas, Maria Soler ; Grankvist, Kjell ; Johansson, Mikael ; Shepherd, Frances A ; Marcus, Michael ; Brunnström, Hans ; Manjer, Jonas ; Melander, Olle ; Muller, David C ; Overvad, Kim ; Trichopoulou, Antonia ; Tumino, Rosaria ; Liu, Geoffrey ; Bojesen, Stig ; Wu, Xifeng ; Le Marchand, Loic ; Albanes, Demetrios ; Bickeböller, Heike ; Aldrich, Melinda C ; Bush, William S ; Tardon, Adonina ; Rennert, Gad ; Teare, M. Dawn ; Field, John K ; Kiemeney, Lambertus A ; Lazarus, Philip ; Haugen, Aage ; Lam, Stephen ; Schabath, Matthew B ; Andrew, Angeline S ; Bertazzi, Pier Alberto ; Pesatori, Angela C ; Christiani, David C ; Caporaso, Neil ; Johansson, Mattias ; McKay, James D ; Brennan, Paul ; Hung, Rayjean J ; Amos, Christopher I</creatorcontrib><description>The development of cancer is driven by the accumulation of many oncogenesis-related genetic alterationsand tumorigenesis is triggered by complex networks of involved genes rather than independent actions. To explore the epistasis existing among oncogenesis-related genes in lung cancer development, we conducted pairwise genetic interaction analyses among 35,031 SNPs from 2027 oncogenesis-related genes. The genotypes from three independent genome-wide association studies including a total of 24,037 lung cancer patients and 20,401 healthy controls with Caucasian ancestry were analyzed in the study. Using a two-stage study design including discovery and replication studies, and stringent Bonferroni correction for multiple statistical analysis, we identified significant genetic interactions between SNPs in RGL1:RAD51B (OR=0.44, p value=3.27x10-11 in overall lung cancer and OR=0.41, p value=9.71x10-11 in non-small cell lung cancer), SYNE1:RNF43 (OR=0.73, p value=1.01x10-12 in adenocarcinoma) and FHIT:TSPAN8 (OR=1.82, p value=7.62x10-11 in squamous cell carcinoma) in our analysis. None of these genes have been identified from previous main effect association studies in lung cancer. Further eQTL gene expression analysis in lung tissues provided information supporting the functional role of the identified epistasis in lung tumorigenesis. Gene set enrichment analysis revealed potential pathways and gene networks underlying molecular mechanisms in overall lung cancer as well as histology subtypes development. Our results provide evidence that genetic interactions between oncogenesis-related genes play an important role in lung tumorigenesis and epistasis analysis, combined with functional annotation, provides a valuable tool for uncovering functional novel susceptibility genes that contribute to lung cancer development by interacting with other modifier genes.</description><identifier>ISSN: 1760-1774</identifier><language>eng</language><creationdate>2019</creationdate><rights>info:eu-repo/semantics/openAccess</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,780,885,26567</link.rule.ids><linktorsrc>$$Uhttp://hdl.handle.net/11250/2992491$$EView_record_in_NORA$$FView_record_in_$$GNORA$$Hfree_for_read</linktorsrc></links><search><creatorcontrib>Li, Yafang</creatorcontrib><creatorcontrib>Xiao, Xiangjun</creatorcontrib><creatorcontrib>Bossé, Yohan</creatorcontrib><creatorcontrib>Gorlova, Olga</creatorcontrib><creatorcontrib>Gorlov, Ivan</creatorcontrib><creatorcontrib>Han, Younghun</creatorcontrib><creatorcontrib>Byun, Jinyoung</creatorcontrib><creatorcontrib>Leighl, Natasha</creatorcontrib><creatorcontrib>Johansen, Jakob S</creatorcontrib><creatorcontrib>Barnett, Matt</creatorcontrib><creatorcontrib>Chen, Chu</creatorcontrib><creatorcontrib>Goodman, Gary</creatorcontrib><creatorcontrib>Cox, Angela</creatorcontrib><creatorcontrib>Taylor, Fiona</creatorcontrib><creatorcontrib>Woll, Penella</creatorcontrib><creatorcontrib>Wichmann, Erich</creatorcontrib><creatorcontrib>Manz, Judith</creatorcontrib><creatorcontrib>Muley, Thomas</creatorcontrib><creatorcontrib>Risch, Angela</creatorcontrib><creatorcontrib>Rosenberger, Albert</creatorcontrib><creatorcontrib>Han, Jiali</creatorcontrib><creatorcontrib>Siminovitch, Katherine</creatorcontrib><creatorcontrib>Arnold, Susanne</creatorcontrib><creatorcontrib>Haura, Eric B</creatorcontrib><creatorcontrib>Bolca, Ciprian</creatorcontrib><creatorcontrib>Holcátová, Ivana</creatorcontrib><creatorcontrib>Janout, Vladimir</creatorcontrib><creatorcontrib>Kontic, Milica</creatorcontrib><creatorcontrib>Lissowska, Jolanta</creatorcontrib><creatorcontrib>Mukeria, Anush</creatorcontrib><creatorcontrib>Ognjanovic, Simona</creatorcontrib><creatorcontrib>Orlowski, Tadeusz M</creatorcontrib><creatorcontrib>Scelo, Ghislaine</creatorcontrib><creatorcontrib>Swiatkowska, Beata</creatorcontrib><creatorcontrib>Zaridze, David</creatorcontrib><creatorcontrib>Bakke, Per S</creatorcontrib><creatorcontrib>Skaug, Vidar</creatorcontrib><creatorcontrib>Zienolddiny, Shanbeh</creatorcontrib><creatorcontrib>Duell, Eric J</creatorcontrib><creatorcontrib>Butler, Lesley M</creatorcontrib><creatorcontrib>Houlston, Richard</creatorcontrib><creatorcontrib>Artigas, Maria Soler</creatorcontrib><creatorcontrib>Grankvist, Kjell</creatorcontrib><creatorcontrib>Johansson, Mikael</creatorcontrib><creatorcontrib>Shepherd, Frances A</creatorcontrib><creatorcontrib>Marcus, Michael</creatorcontrib><creatorcontrib>Brunnström, Hans</creatorcontrib><creatorcontrib>Manjer, Jonas</creatorcontrib><creatorcontrib>Melander, Olle</creatorcontrib><creatorcontrib>Muller, David C</creatorcontrib><creatorcontrib>Overvad, Kim</creatorcontrib><creatorcontrib>Trichopoulou, Antonia</creatorcontrib><creatorcontrib>Tumino, Rosaria</creatorcontrib><creatorcontrib>Liu, Geoffrey</creatorcontrib><creatorcontrib>Bojesen, Stig</creatorcontrib><creatorcontrib>Wu, Xifeng</creatorcontrib><creatorcontrib>Le Marchand, Loic</creatorcontrib><creatorcontrib>Albanes, Demetrios</creatorcontrib><creatorcontrib>Bickeböller, Heike</creatorcontrib><creatorcontrib>Aldrich, Melinda C</creatorcontrib><creatorcontrib>Bush, William S</creatorcontrib><creatorcontrib>Tardon, Adonina</creatorcontrib><creatorcontrib>Rennert, Gad</creatorcontrib><creatorcontrib>Teare, M. Dawn</creatorcontrib><creatorcontrib>Field, John K</creatorcontrib><creatorcontrib>Kiemeney, Lambertus A</creatorcontrib><creatorcontrib>Lazarus, Philip</creatorcontrib><creatorcontrib>Haugen, Aage</creatorcontrib><creatorcontrib>Lam, Stephen</creatorcontrib><creatorcontrib>Schabath, Matthew B</creatorcontrib><creatorcontrib>Andrew, Angeline S</creatorcontrib><creatorcontrib>Bertazzi, Pier Alberto</creatorcontrib><creatorcontrib>Pesatori, Angela C</creatorcontrib><creatorcontrib>Christiani, David C</creatorcontrib><creatorcontrib>Caporaso, Neil</creatorcontrib><creatorcontrib>Johansson, Mattias</creatorcontrib><creatorcontrib>McKay, James D</creatorcontrib><creatorcontrib>Brennan, Paul</creatorcontrib><creatorcontrib>Hung, Rayjean J</creatorcontrib><creatorcontrib>Amos, Christopher I</creatorcontrib><title>Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development</title><description>The development of cancer is driven by the accumulation of many oncogenesis-related genetic alterationsand tumorigenesis is triggered by complex networks of involved genes rather than independent actions. To explore the epistasis existing among oncogenesis-related genes in lung cancer development, we conducted pairwise genetic interaction analyses among 35,031 SNPs from 2027 oncogenesis-related genes. The genotypes from three independent genome-wide association studies including a total of 24,037 lung cancer patients and 20,401 healthy controls with Caucasian ancestry were analyzed in the study. Using a two-stage study design including discovery and replication studies, and stringent Bonferroni correction for multiple statistical analysis, we identified significant genetic interactions between SNPs in RGL1:RAD51B (OR=0.44, p value=3.27x10-11 in overall lung cancer and OR=0.41, p value=9.71x10-11 in non-small cell lung cancer), SYNE1:RNF43 (OR=0.73, p value=1.01x10-12 in adenocarcinoma) and FHIT:TSPAN8 (OR=1.82, p value=7.62x10-11 in squamous cell carcinoma) in our analysis. None of these genes have been identified from previous main effect association studies in lung cancer. Further eQTL gene expression analysis in lung tissues provided information supporting the functional role of the identified epistasis in lung tumorigenesis. Gene set enrichment analysis revealed potential pathways and gene networks underlying molecular mechanisms in overall lung cancer as well as histology subtypes development. Our results provide evidence that genetic interactions between oncogenesis-related genes play an important role in lung tumorigenesis and epistasis analysis, combined with functional annotation, provides a valuable tool for uncovering functional novel susceptibility genes that contribute to lung cancer development by interacting with other modifier genes.</description><issn>1760-1774</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>3HK</sourceid><recordid>eNqNjE0OgjAQhbvQBVHvMB6AhCJIWBt_DuCeTMpIGsuMaSuG29sYDuDq5Xv53lupTDfHItdNU2VqvhJTtAYsR_JoohUGZHRzsAFwFB5A2MiQtNTknhxG6uHH4GkidAlZJnJLiZyY4kf8M6RbcO_0YZANeejTwMlrJI5btX6gC7RbcqP2l_P9dMuNtyFa7lg8dlqXddGVbVtWrT7843wBF6BJCw</recordid><startdate>2019</startdate><enddate>2019</enddate><creator>Li, Yafang</creator><creator>Xiao, Xiangjun</creator><creator>Bossé, Yohan</creator><creator>Gorlova, Olga</creator><creator>Gorlov, Ivan</creator><creator>Han, Younghun</creator><creator>Byun, Jinyoung</creator><creator>Leighl, Natasha</creator><creator>Johansen, Jakob S</creator><creator>Barnett, Matt</creator><creator>Chen, Chu</creator><creator>Goodman, Gary</creator><creator>Cox, Angela</creator><creator>Taylor, Fiona</creator><creator>Woll, Penella</creator><creator>Wichmann, Erich</creator><creator>Manz, Judith</creator><creator>Muley, Thomas</creator><creator>Risch, Angela</creator><creator>Rosenberger, Albert</creator><creator>Han, Jiali</creator><creator>Siminovitch, Katherine</creator><creator>Arnold, Susanne</creator><creator>Haura, Eric B</creator><creator>Bolca, Ciprian</creator><creator>Holcátová, Ivana</creator><creator>Janout, Vladimir</creator><creator>Kontic, Milica</creator><creator>Lissowska, Jolanta</creator><creator>Mukeria, Anush</creator><creator>Ognjanovic, Simona</creator><creator>Orlowski, Tadeusz M</creator><creator>Scelo, Ghislaine</creator><creator>Swiatkowska, Beata</creator><creator>Zaridze, David</creator><creator>Bakke, Per S</creator><creator>Skaug, Vidar</creator><creator>Zienolddiny, Shanbeh</creator><creator>Duell, Eric J</creator><creator>Butler, Lesley M</creator><creator>Houlston, Richard</creator><creator>Artigas, Maria Soler</creator><creator>Grankvist, Kjell</creator><creator>Johansson, Mikael</creator><creator>Shepherd, Frances A</creator><creator>Marcus, Michael</creator><creator>Brunnström, Hans</creator><creator>Manjer, Jonas</creator><creator>Melander, Olle</creator><creator>Muller, David C</creator><creator>Overvad, Kim</creator><creator>Trichopoulou, Antonia</creator><creator>Tumino, Rosaria</creator><creator>Liu, Geoffrey</creator><creator>Bojesen, Stig</creator><creator>Wu, Xifeng</creator><creator>Le Marchand, Loic</creator><creator>Albanes, Demetrios</creator><creator>Bickeböller, Heike</creator><creator>Aldrich, Melinda C</creator><creator>Bush, William S</creator><creator>Tardon, Adonina</creator><creator>Rennert, Gad</creator><creator>Teare, M. Dawn</creator><creator>Field, John K</creator><creator>Kiemeney, Lambertus A</creator><creator>Lazarus, Philip</creator><creator>Haugen, Aage</creator><creator>Lam, Stephen</creator><creator>Schabath, Matthew B</creator><creator>Andrew, Angeline S</creator><creator>Bertazzi, Pier Alberto</creator><creator>Pesatori, Angela C</creator><creator>Christiani, David C</creator><creator>Caporaso, Neil</creator><creator>Johansson, Mattias</creator><creator>McKay, James D</creator><creator>Brennan, Paul</creator><creator>Hung, Rayjean J</creator><creator>Amos, Christopher I</creator><scope>3HK</scope></search><sort><creationdate>2019</creationdate><title>Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development</title><author>Li, Yafang ; Xiao, Xiangjun ; Bossé, Yohan ; Gorlova, Olga ; Gorlov, Ivan ; Han, Younghun ; Byun, Jinyoung ; Leighl, Natasha ; Johansen, Jakob S ; Barnett, Matt ; Chen, Chu ; Goodman, Gary ; Cox, Angela ; Taylor, Fiona ; Woll, Penella ; Wichmann, Erich ; Manz, Judith ; Muley, Thomas ; Risch, Angela ; Rosenberger, Albert ; Han, Jiali ; Siminovitch, Katherine ; Arnold, Susanne ; Haura, Eric B ; Bolca, Ciprian ; Holcátová, Ivana ; Janout, Vladimir ; Kontic, Milica ; Lissowska, Jolanta ; Mukeria, Anush ; Ognjanovic, Simona ; Orlowski, Tadeusz M ; Scelo, Ghislaine ; Swiatkowska, Beata ; Zaridze, David ; Bakke, Per S ; Skaug, Vidar ; Zienolddiny, Shanbeh ; Duell, Eric J ; Butler, Lesley M ; Houlston, Richard ; Artigas, Maria Soler ; Grankvist, Kjell ; Johansson, Mikael ; Shepherd, Frances A ; Marcus, Michael ; Brunnström, Hans ; Manjer, Jonas ; Melander, Olle ; Muller, David C ; Overvad, Kim ; Trichopoulou, Antonia ; Tumino, Rosaria ; Liu, Geoffrey ; Bojesen, Stig ; Wu, Xifeng ; Le Marchand, Loic ; Albanes, Demetrios ; Bickeböller, Heike ; Aldrich, Melinda C ; Bush, William S ; Tardon, Adonina ; Rennert, Gad ; Teare, M. Dawn ; Field, John K ; Kiemeney, Lambertus A ; Lazarus, Philip ; Haugen, Aage ; Lam, Stephen ; Schabath, Matthew B ; Andrew, Angeline S ; Bertazzi, Pier Alberto ; Pesatori, Angela C ; Christiani, David C ; Caporaso, Neil ; Johansson, Mattias ; McKay, James D ; Brennan, Paul ; Hung, Rayjean J ; Amos, Christopher I</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-cristin_nora_11250_29924913</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><toplevel>online_resources</toplevel><creatorcontrib>Li, Yafang</creatorcontrib><creatorcontrib>Xiao, Xiangjun</creatorcontrib><creatorcontrib>Bossé, Yohan</creatorcontrib><creatorcontrib>Gorlova, Olga</creatorcontrib><creatorcontrib>Gorlov, Ivan</creatorcontrib><creatorcontrib>Han, Younghun</creatorcontrib><creatorcontrib>Byun, Jinyoung</creatorcontrib><creatorcontrib>Leighl, Natasha</creatorcontrib><creatorcontrib>Johansen, Jakob S</creatorcontrib><creatorcontrib>Barnett, Matt</creatorcontrib><creatorcontrib>Chen, Chu</creatorcontrib><creatorcontrib>Goodman, Gary</creatorcontrib><creatorcontrib>Cox, Angela</creatorcontrib><creatorcontrib>Taylor, Fiona</creatorcontrib><creatorcontrib>Woll, Penella</creatorcontrib><creatorcontrib>Wichmann, Erich</creatorcontrib><creatorcontrib>Manz, Judith</creatorcontrib><creatorcontrib>Muley, Thomas</creatorcontrib><creatorcontrib>Risch, Angela</creatorcontrib><creatorcontrib>Rosenberger, Albert</creatorcontrib><creatorcontrib>Han, Jiali</creatorcontrib><creatorcontrib>Siminovitch, Katherine</creatorcontrib><creatorcontrib>Arnold, Susanne</creatorcontrib><creatorcontrib>Haura, Eric B</creatorcontrib><creatorcontrib>Bolca, Ciprian</creatorcontrib><creatorcontrib>Holcátová, Ivana</creatorcontrib><creatorcontrib>Janout, Vladimir</creatorcontrib><creatorcontrib>Kontic, Milica</creatorcontrib><creatorcontrib>Lissowska, Jolanta</creatorcontrib><creatorcontrib>Mukeria, Anush</creatorcontrib><creatorcontrib>Ognjanovic, Simona</creatorcontrib><creatorcontrib>Orlowski, Tadeusz M</creatorcontrib><creatorcontrib>Scelo, Ghislaine</creatorcontrib><creatorcontrib>Swiatkowska, Beata</creatorcontrib><creatorcontrib>Zaridze, David</creatorcontrib><creatorcontrib>Bakke, Per S</creatorcontrib><creatorcontrib>Skaug, Vidar</creatorcontrib><creatorcontrib>Zienolddiny, Shanbeh</creatorcontrib><creatorcontrib>Duell, Eric J</creatorcontrib><creatorcontrib>Butler, Lesley M</creatorcontrib><creatorcontrib>Houlston, Richard</creatorcontrib><creatorcontrib>Artigas, Maria Soler</creatorcontrib><creatorcontrib>Grankvist, Kjell</creatorcontrib><creatorcontrib>Johansson, Mikael</creatorcontrib><creatorcontrib>Shepherd, Frances A</creatorcontrib><creatorcontrib>Marcus, Michael</creatorcontrib><creatorcontrib>Brunnström, Hans</creatorcontrib><creatorcontrib>Manjer, Jonas</creatorcontrib><creatorcontrib>Melander, Olle</creatorcontrib><creatorcontrib>Muller, David C</creatorcontrib><creatorcontrib>Overvad, Kim</creatorcontrib><creatorcontrib>Trichopoulou, Antonia</creatorcontrib><creatorcontrib>Tumino, Rosaria</creatorcontrib><creatorcontrib>Liu, Geoffrey</creatorcontrib><creatorcontrib>Bojesen, Stig</creatorcontrib><creatorcontrib>Wu, Xifeng</creatorcontrib><creatorcontrib>Le Marchand, Loic</creatorcontrib><creatorcontrib>Albanes, Demetrios</creatorcontrib><creatorcontrib>Bickeböller, Heike</creatorcontrib><creatorcontrib>Aldrich, Melinda C</creatorcontrib><creatorcontrib>Bush, William S</creatorcontrib><creatorcontrib>Tardon, Adonina</creatorcontrib><creatorcontrib>Rennert, Gad</creatorcontrib><creatorcontrib>Teare, M. Dawn</creatorcontrib><creatorcontrib>Field, John K</creatorcontrib><creatorcontrib>Kiemeney, Lambertus A</creatorcontrib><creatorcontrib>Lazarus, Philip</creatorcontrib><creatorcontrib>Haugen, Aage</creatorcontrib><creatorcontrib>Lam, Stephen</creatorcontrib><creatorcontrib>Schabath, Matthew B</creatorcontrib><creatorcontrib>Andrew, Angeline S</creatorcontrib><creatorcontrib>Bertazzi, Pier Alberto</creatorcontrib><creatorcontrib>Pesatori, Angela C</creatorcontrib><creatorcontrib>Christiani, David C</creatorcontrib><creatorcontrib>Caporaso, Neil</creatorcontrib><creatorcontrib>Johansson, Mattias</creatorcontrib><creatorcontrib>McKay, James D</creatorcontrib><creatorcontrib>Brennan, Paul</creatorcontrib><creatorcontrib>Hung, Rayjean J</creatorcontrib><creatorcontrib>Amos, Christopher I</creatorcontrib><collection>NORA - Norwegian Open Research Archives</collection></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Li, Yafang</au><au>Xiao, Xiangjun</au><au>Bossé, Yohan</au><au>Gorlova, Olga</au><au>Gorlov, Ivan</au><au>Han, Younghun</au><au>Byun, Jinyoung</au><au>Leighl, Natasha</au><au>Johansen, Jakob S</au><au>Barnett, Matt</au><au>Chen, Chu</au><au>Goodman, Gary</au><au>Cox, Angela</au><au>Taylor, Fiona</au><au>Woll, Penella</au><au>Wichmann, Erich</au><au>Manz, Judith</au><au>Muley, Thomas</au><au>Risch, Angela</au><au>Rosenberger, Albert</au><au>Han, Jiali</au><au>Siminovitch, Katherine</au><au>Arnold, Susanne</au><au>Haura, Eric B</au><au>Bolca, Ciprian</au><au>Holcátová, Ivana</au><au>Janout, Vladimir</au><au>Kontic, Milica</au><au>Lissowska, Jolanta</au><au>Mukeria, Anush</au><au>Ognjanovic, Simona</au><au>Orlowski, Tadeusz M</au><au>Scelo, Ghislaine</au><au>Swiatkowska, Beata</au><au>Zaridze, David</au><au>Bakke, Per S</au><au>Skaug, Vidar</au><au>Zienolddiny, Shanbeh</au><au>Duell, Eric J</au><au>Butler, Lesley M</au><au>Houlston, Richard</au><au>Artigas, Maria Soler</au><au>Grankvist, Kjell</au><au>Johansson, Mikael</au><au>Shepherd, Frances A</au><au>Marcus, Michael</au><au>Brunnström, Hans</au><au>Manjer, Jonas</au><au>Melander, Olle</au><au>Muller, David C</au><au>Overvad, Kim</au><au>Trichopoulou, Antonia</au><au>Tumino, Rosaria</au><au>Liu, Geoffrey</au><au>Bojesen, Stig</au><au>Wu, Xifeng</au><au>Le Marchand, Loic</au><au>Albanes, Demetrios</au><au>Bickeböller, Heike</au><au>Aldrich, Melinda C</au><au>Bush, William S</au><au>Tardon, Adonina</au><au>Rennert, Gad</au><au>Teare, M. Dawn</au><au>Field, John K</au><au>Kiemeney, Lambertus A</au><au>Lazarus, Philip</au><au>Haugen, Aage</au><au>Lam, Stephen</au><au>Schabath, Matthew B</au><au>Andrew, Angeline S</au><au>Bertazzi, Pier Alberto</au><au>Pesatori, Angela C</au><au>Christiani, David C</au><au>Caporaso, Neil</au><au>Johansson, Mattias</au><au>McKay, James D</au><au>Brennan, Paul</au><au>Hung, Rayjean J</au><au>Amos, Christopher I</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development</atitle><date>2019</date><risdate>2019</risdate><issn>1760-1774</issn><abstract>The development of cancer is driven by the accumulation of many oncogenesis-related genetic alterationsand tumorigenesis is triggered by complex networks of involved genes rather than independent actions. To explore the epistasis existing among oncogenesis-related genes in lung cancer development, we conducted pairwise genetic interaction analyses among 35,031 SNPs from 2027 oncogenesis-related genes. The genotypes from three independent genome-wide association studies including a total of 24,037 lung cancer patients and 20,401 healthy controls with Caucasian ancestry were analyzed in the study. Using a two-stage study design including discovery and replication studies, and stringent Bonferroni correction for multiple statistical analysis, we identified significant genetic interactions between SNPs in RGL1:RAD51B (OR=0.44, p value=3.27x10-11 in overall lung cancer and OR=0.41, p value=9.71x10-11 in non-small cell lung cancer), SYNE1:RNF43 (OR=0.73, p value=1.01x10-12 in adenocarcinoma) and FHIT:TSPAN8 (OR=1.82, p value=7.62x10-11 in squamous cell carcinoma) in our analysis. None of these genes have been identified from previous main effect association studies in lung cancer. Further eQTL gene expression analysis in lung tissues provided information supporting the functional role of the identified epistasis in lung tumorigenesis. Gene set enrichment analysis revealed potential pathways and gene networks underlying molecular mechanisms in overall lung cancer as well as histology subtypes development. Our results provide evidence that genetic interactions between oncogenesis-related genes play an important role in lung tumorigenesis and epistasis analysis, combined with functional annotation, provides a valuable tool for uncovering functional novel susceptibility genes that contribute to lung cancer development by interacting with other modifier genes.</abstract><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext_linktorsrc |
| identifier | ISSN: 1760-1774 |
| ispartof | |
| issn | 1760-1774 |
| language | eng |
| recordid | cdi_cristin_nora_11250_2992491 |
| source | NORA - Norwegian Open Research Archives |
| title | Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development |
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