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Start Over Author "Qian, David" Publisher umea universitet, onkologi
13 results on '"Qian, David"'

1. Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity

Author

Ferreiro-Iglesias, Aida, Lesseur, Corina, McKay, James, Hung, Rayjean J., Han, Younghun, Zong, Xuchen, Christiani, David, Johansson, Mattias, Xiao, Xiangjun, Li, Yafang, Qian, David C., Ji, Xuemei, Liu, Geoffrey, Caporaso, Neil, Scelo, Ghislaine, Zaridze, David, Mukeriya, Anush, Kontic, Milica, Ognjanovic, Simona, Lissowska, Jolanta, Szolkowska, Malgorzata, Swiatkowska, Beata, Janout, Vladimir, Holcatova, Ivana, Bolca, Ciprian, Savic, Milan, Ognjanovic, Miodrag, Bojesen, Stig Egil, Wu, Xifeng, Albanes, Demetrios, Aldrich, Melinda C., Tardon, Adonina, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, Le Marchand, Loic, Rennert, Gadi, Chen, Chu, Doherty, Jennifer, Goodman, Gary, Bickeboeller, Heike, Wichmann, H-Erich, Risch, Angela, Rosenberger, Albert, Shen, Hongbing, Dai, Juncheng, Field, John K., Davies, Michael, Woll, Penella, Teare, M. Dawn, Kiemeney, Lambertus A., van der Heijden, Erik H. F. M., Yuan, Jian-Min, Hong, Yun-Chul, Haugen, Aage, Zienolddiny, Shanbeh, Lam, Stephen, Tsao, Ming-Sound, Johansson, Mikael, Grankvist, Kjell, Schabath, Matthew B., Andrew, Angeline, Duell, Eric, Melander, Olle, Brunnstrom, Hans, Lazarus, Philip, Arnold, Susanne, Slone, Stacey, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Landi, Maria Teresa, Amos, Christopher, I, Brennan, Paul, Ferreiro-Iglesias, Aida, Lesseur, Corina, McKay, James, Hung, Rayjean J., Han, Younghun, Zong, Xuchen, Christiani, David, Johansson, Mattias, Xiao, Xiangjun, Li, Yafang, Qian, David C., Ji, Xuemei, Liu, Geoffrey, Caporaso, Neil, Scelo, Ghislaine, Zaridze, David, Mukeriya, Anush, Kontic, Milica, Ognjanovic, Simona, Lissowska, Jolanta, Szolkowska, Malgorzata, Swiatkowska, Beata, Janout, Vladimir, Holcatova, Ivana, Bolca, Ciprian, Savic, Milan, Ognjanovic, Miodrag, Bojesen, Stig Egil, Wu, Xifeng, Albanes, Demetrios, Aldrich, Melinda C., Tardon, Adonina, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, Le Marchand, Loic, Rennert, Gadi, Chen, Chu, Doherty, Jennifer, Goodman, Gary, Bickeboeller, Heike, Wichmann, H-Erich, Risch, Angela, Rosenberger, Albert, Shen, Hongbing, Dai, Juncheng, Field, John K., Davies, Michael, Woll, Penella, Teare, M. Dawn, Kiemeney, Lambertus A., van der Heijden, Erik H. F. M., Yuan, Jian-Min, Hong, Yun-Chul, Haugen, Aage, Zienolddiny, Shanbeh, Lam, Stephen, Tsao, Ming-Sound, Johansson, Mikael, Grankvist, Kjell, Schabath, Matthew B., Andrew, Angeline, Duell, Eric, Melander, Olle, Brunnstrom, Hans, Lazarus, Philip, Arnold, Susanne, Slone, Stacey, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Landi, Maria Teresa, Amos, Christopher, I, and Brennan, Paul

Abstract

Lung cancer has several genetic associations identified within the major histocompatibility complex (MHC); although the basis for these associations remains elusive. Here, we analyze MHC genetic variation among 26,044 lung cancer patients and 20,836 controls densely genotyped across the MHC, using the Illumina Illumina OncoArray or Illumina 660W SNP microarray. We impute sequence variation in classical HLA genes, fine-map MHC associations for lung cancer risk with major histologies and compare results between ethnicities. Independent and novel associations within HLA genes are identified in Europeans including amino acids in the HLA-B*0801 peptide binding groove and an independent HLA-DQB1*06 loci group. In Asians, associations are driven by two independent HLA allele sets that both increase risk in HLA-DQB1*0401 and HLA-DRB1*0701; the latter better represented by the amino acid Ala-104. These results implicate several HLA-tumor peptide interactions as the major MHC factor modulating lung cancer susceptibility.

Published
2018
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2. Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity

Author

Ferreiro-Iglesias, Aida, Lesseur, Corina, McKay, James, Hung, Rayjean J., Han, Younghun, Zong, Xuchen, Christiani, David, Johansson, Mattias, Xiao, Xiangjun, Li, Yafang, Qian, David C., Ji, Xuemei, Liu, Geoffrey, Caporaso, Neil, Scelo, Ghislaine, Zaridze, David, Mukeriya, Anush, Kontic, Milica, Ognjanovic, Simona, Lissowska, Jolanta, Szolkowska, Malgorzata, Swiatkowska, Beata, Janout, Vladimir, Holcatova, Ivana, Bolca, Ciprian, Savic, Milan, Ognjanovic, Miodrag, Bojesen, Stig Egil, Wu, Xifeng, Albanes, Demetrios, Aldrich, Melinda C., Tardon, Adonina, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, Le Marchand, Loic, Rennert, Gadi, Chen, Chu, Doherty, Jennifer, Goodman, Gary, Bickeboeller, Heike, Wichmann, H-Erich, Risch, Angela, Rosenberger, Albert, Shen, Hongbing, Dai, Juncheng, Field, John K., Davies, Michael, Woll, Penella, Teare, M. Dawn, Kiemeney, Lambertus A., van der Heijden, Erik H. F. M., Yuan, Jian-Min, Hong, Yun-Chul, Haugen, Aage, Zienolddiny, Shanbeh, Lam, Stephen, Tsao, Ming-Sound, Johansson, Mikael, Grankvist, Kjell, Schabath, Matthew B., Andrew, Angeline, Duell, Eric, Melander, Olle, Brunnstrom, Hans, Lazarus, Philip, Arnold, Susanne, Slone, Stacey, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Landi, Maria Teresa, Amos, Christopher, I, Brennan, Paul, Ferreiro-Iglesias, Aida, Lesseur, Corina, McKay, James, Hung, Rayjean J., Han, Younghun, Zong, Xuchen, Christiani, David, Johansson, Mattias, Xiao, Xiangjun, Li, Yafang, Qian, David C., Ji, Xuemei, Liu, Geoffrey, Caporaso, Neil, Scelo, Ghislaine, Zaridze, David, Mukeriya, Anush, Kontic, Milica, Ognjanovic, Simona, Lissowska, Jolanta, Szolkowska, Malgorzata, Swiatkowska, Beata, Janout, Vladimir, Holcatova, Ivana, Bolca, Ciprian, Savic, Milan, Ognjanovic, Miodrag, Bojesen, Stig Egil, Wu, Xifeng, Albanes, Demetrios, Aldrich, Melinda C., Tardon, Adonina, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, Le Marchand, Loic, Rennert, Gadi, Chen, Chu, Doherty, Jennifer, Goodman, Gary, Bickeboeller, Heike, Wichmann, H-Erich, Risch, Angela, Rosenberger, Albert, Shen, Hongbing, Dai, Juncheng, Field, John K., Davies, Michael, Woll, Penella, Teare, M. Dawn, Kiemeney, Lambertus A., van der Heijden, Erik H. F. M., Yuan, Jian-Min, Hong, Yun-Chul, Haugen, Aage, Zienolddiny, Shanbeh, Lam, Stephen, Tsao, Ming-Sound, Johansson, Mikael, Grankvist, Kjell, Schabath, Matthew B., Andrew, Angeline, Duell, Eric, Melander, Olle, Brunnstrom, Hans, Lazarus, Philip, Arnold, Susanne, Slone, Stacey, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Landi, Maria Teresa, Amos, Christopher, I, and Brennan, Paul

Abstract

Lung cancer has several genetic associations identified within the major histocompatibility complex (MHC); although the basis for these associations remains elusive. Here, we analyze MHC genetic variation among 26,044 lung cancer patients and 20,836 controls densely genotyped across the MHC, using the Illumina Illumina OncoArray or Illumina 660W SNP microarray. We impute sequence variation in classical HLA genes, fine-map MHC associations for lung cancer risk with major histologies and compare results between ethnicities. Independent and novel associations within HLA genes are identified in Europeans including amino acids in the HLA-B*0801 peptide binding groove and an independent HLA-DQB1*06 loci group. In Asians, associations are driven by two independent HLA allele sets that both increase risk in HLA-DQB1*0401 and HLA-DRB1*0701; the latter better represented by the amino acid Ala-104. These results implicate several HLA-tumor peptide interactions as the major MHC factor modulating lung cancer susceptibility.

Published
2018
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3. Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population

Author

Li, Yafang, Xiao, Xiangjun, Han, Younghun, Gorlova, Olga, Qian, David, Leighl, Natasha, Johansen, Jakob S., Barnett, Matt, Chen, Chu, Goodman, Gary, Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, H-Erich, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, 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, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Houlston, Richard, Artigas, María Soler, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Liu, Geoffrey, Bojesen, Stig E., 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., Li, Yafang, Xiao, Xiangjun, Han, Younghun, Gorlova, Olga, Qian, David, Leighl, Natasha, Johansen, Jakob S., Barnett, Matt, Chen, Chu, Goodman, Gary, Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, H-Erich, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, 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, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Houlston, Richard, Artigas, María Soler, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Liu, Geoffrey, Bojesen, Stig E., 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., and Amos, Christopher I.

Abstract

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Both environmental and genetic risk factors contribute to lung carcinogenesis. We conducted a genome-wide interaction analysis between SNPs and smoking status (never vs ever smokers) in a European-descent population. We adopted a two-step analysis strategy in the discovery stage: we first conducted a case-only interaction analysis to assess the relationship between SNPs and smoking behavior using 13,336 NSCLC cases. Candidate SNPs with p-value less than 0.001 were further analyzed using a standard case-control interaction analysis including 13970 controls. The significant SNPs with p-value less than 3.5x10-5 (correcting for multiple tests) from the case-control analysis in the discovery stage were further validated using an independent replication dataset comprising 5377 controls and 3054 NSCLC cases. We further stratified the analysis by histological subtypes. Two novel SNPs, rs6441286 and rs17723637, were identified for overall lung cancer risk. The interaction odds ratio and meta-analysis p-value for these two SNPs were 1.24 with 6.96x10-7 and 1.37 with 3.49x10-7, respectively. Additionally, interaction of smoking with rs4751674 was identified in squamous cell lung carcinoma with an odds ratio of 0.58 and p-value of 8.12x10-7. This study is by far the largest genome-wide SNP-smoking interaction analysis reported for lung cancer. The three identified novel SNPs provide potential candidate biomarkers for lung cancer risk screening and intervention. The results from our study reinforce that gene-smoking interactions play important roles in the etiology of lung cancer and account for part of the missing heritability of this disease.

Published
2018
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4. Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity

Author

Ferreiro-Iglesias, Aida, Lesseur, Corina, McKay, James, Hung, Rayjean J., Han, Younghun, Zong, Xuchen, Christiani, David, Johansson, Mattias, Xiao, Xiangjun, Li, Yafang, Qian, David C., Ji, Xuemei, Liu, Geoffrey, Caporaso, Neil, Scelo, Ghislaine, Zaridze, David, Mukeriya, Anush, Kontic, Milica, Ognjanovic, Simona, Lissowska, Jolanta, Szolkowska, Malgorzata, Swiatkowska, Beata, Janout, Vladimir, Holcatova, Ivana, Bolca, Ciprian, Savic, Milan, Ognjanovic, Miodrag, Bojesen, Stig Egil, Wu, Xifeng, Albanes, Demetrios, Aldrich, Melinda C., Tardon, Adonina, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, Le Marchand, Loic, Rennert, Gadi, Chen, Chu, Doherty, Jennifer, Goodman, Gary, Bickeboeller, Heike, Wichmann, H-Erich, Risch, Angela, Rosenberger, Albert, Shen, Hongbing, Dai, Juncheng, Field, John K., Davies, Michael, Woll, Penella, Teare, M. Dawn, Kiemeney, Lambertus A., van der Heijden, Erik H. F. M., Yuan, Jian-Min, Hong, Yun-Chul, Haugen, Aage, Zienolddiny, Shanbeh, Lam, Stephen, Tsao, Ming-Sound, Johansson, Mikael, Grankvist, Kjell, Schabath, Matthew B., Andrew, Angeline, Duell, Eric, Melander, Olle, Brunnstrom, Hans, Lazarus, Philip, Arnold, Susanne, Slone, Stacey, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Landi, Maria Teresa, Amos, Christopher, I, Brennan, Paul, Ferreiro-Iglesias, Aida, Lesseur, Corina, McKay, James, Hung, Rayjean J., Han, Younghun, Zong, Xuchen, Christiani, David, Johansson, Mattias, Xiao, Xiangjun, Li, Yafang, Qian, David C., Ji, Xuemei, Liu, Geoffrey, Caporaso, Neil, Scelo, Ghislaine, Zaridze, David, Mukeriya, Anush, Kontic, Milica, Ognjanovic, Simona, Lissowska, Jolanta, Szolkowska, Malgorzata, Swiatkowska, Beata, Janout, Vladimir, Holcatova, Ivana, Bolca, Ciprian, Savic, Milan, Ognjanovic, Miodrag, Bojesen, Stig Egil, Wu, Xifeng, Albanes, Demetrios, Aldrich, Melinda C., Tardon, Adonina, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, Le Marchand, Loic, Rennert, Gadi, Chen, Chu, Doherty, Jennifer, Goodman, Gary, Bickeboeller, Heike, Wichmann, H-Erich, Risch, Angela, Rosenberger, Albert, Shen, Hongbing, Dai, Juncheng, Field, John K., Davies, Michael, Woll, Penella, Teare, M. Dawn, Kiemeney, Lambertus A., van der Heijden, Erik H. F. M., Yuan, Jian-Min, Hong, Yun-Chul, Haugen, Aage, Zienolddiny, Shanbeh, Lam, Stephen, Tsao, Ming-Sound, Johansson, Mikael, Grankvist, Kjell, Schabath, Matthew B., Andrew, Angeline, Duell, Eric, Melander, Olle, Brunnstrom, Hans, Lazarus, Philip, Arnold, Susanne, Slone, Stacey, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Landi, Maria Teresa, Amos, Christopher, I, and Brennan, Paul

Abstract

Lung cancer has several genetic associations identified within the major histocompatibility complex (MHC); although the basis for these associations remains elusive. Here, we analyze MHC genetic variation among 26,044 lung cancer patients and 20,836 controls densely genotyped across the MHC, using the Illumina Illumina OncoArray or Illumina 660W SNP microarray. We impute sequence variation in classical HLA genes, fine-map MHC associations for lung cancer risk with major histologies and compare results between ethnicities. Independent and novel associations within HLA genes are identified in Europeans including amino acids in the HLA-B*0801 peptide binding groove and an independent HLA-DQB1*06 loci group. In Asians, associations are driven by two independent HLA allele sets that both increase risk in HLA-DQB1*0401 and HLA-DRB1*0701; the latter better represented by the amino acid Ala-104. These results implicate several HLA-tumor peptide interactions as the major MHC factor modulating lung cancer susceptibility.

Published
2018
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5. Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk

Author

Ji, Xuemei, Bosse, Yohan, Landi, Maria Teresa, Gui, Jiang, Xiao, Xiangjun, Qian, David, Joubert, Philippe, Lamontagne, Maxime, Li, Yafang, Gorlov, Ivan, de Biasi, Mariella, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Wu, Xifeng, Mckay, James, Zong, Xuchen, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Shen, Hongbing, Hong, Yun-Chul, Yuan, Jian-Min, Bertazzi, Pier A., Pesatori, Angela C., Ye, Yuanqing, Diao, Nancy, Su, Li, Zhang, Ruyang, Brhane, Yonathan, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Dai, Juncheng, Hu, Zhibin, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Doherty, Jennifer, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Brueske, Irene, Manz, Judith, 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, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Koh, Woon-Puay, Gao, Yu-Tang, Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, Ma'en, Timens, Wim, Zhu, Bin, Song, Lei, Artigas, Maria Soler, Tobin, Martin D., Wain, Louise V., Gu, Fangyi, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Tyndale, Rachel F., Wei, Wei-Qi, Chanock, Stephen, Brennan, Paul, Amos, Christopher I., Ji, Xuemei, Bosse, Yohan, Landi, Maria Teresa, Gui, Jiang, Xiao, Xiangjun, Qian, David, Joubert, Philippe, Lamontagne, Maxime, Li, Yafang, Gorlov, Ivan, de Biasi, Mariella, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Wu, Xifeng, Mckay, James, Zong, Xuchen, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Shen, Hongbing, Hong, Yun-Chul, Yuan, Jian-Min, Bertazzi, Pier A., Pesatori, Angela C., Ye, Yuanqing, Diao, Nancy, Su, Li, Zhang, Ruyang, Brhane, Yonathan, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Dai, Juncheng, Hu, Zhibin, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Doherty, Jennifer, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Brueske, Irene, Manz, Judith, 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, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Koh, Woon-Puay, Gao, Yu-Tang, Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, Ma'en, Timens, Wim, Zhu, Bin, Song, Lei, Artigas, Maria Soler, Tobin, Martin D., Wain, Louise V., Gu, Fangyi, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Tyndale, Rachel F., Wei, Wei-Qi, Chanock, Stephen, Brennan, Paul, and Amos, Christopher I.

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.

Published
2018
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6. Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity

Author

Ferreiro-Iglesias, Aida, Lesseur, Corina, McKay, James, Hung, Rayjean J., Han, Younghun, Zong, Xuchen, Christiani, David, Johansson, Mattias, Xiao, Xiangjun, Li, Yafang, Qian, David C., Ji, Xuemei, Liu, Geoffrey, Caporaso, Neil, Scelo, Ghislaine, Zaridze, David, Mukeriya, Anush, Kontic, Milica, Ognjanovic, Simona, Lissowska, Jolanta, Szolkowska, Malgorzata, Swiatkowska, Beata, Janout, Vladimir, Holcatova, Ivana, Bolca, Ciprian, Savic, Milan, Ognjanovic, Miodrag, Bojesen, Stig Egil, Wu, Xifeng, Albanes, Demetrios, Aldrich, Melinda C., Tardon, Adonina, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, Le Marchand, Loic, Rennert, Gadi, Chen, Chu, Doherty, Jennifer, Goodman, Gary, Bickeboeller, Heike, Wichmann, H-Erich, Risch, Angela, Rosenberger, Albert, Shen, Hongbing, Dai, Juncheng, Field, John K., Davies, Michael, Woll, Penella, Teare, M. Dawn, Kiemeney, Lambertus A., van der Heijden, Erik H. F. M., Yuan, Jian-Min, Hong, Yun-Chul, Haugen, Aage, Zienolddiny, Shanbeh, Lam, Stephen, Tsao, Ming-Sound, Johansson, Mikael, Grankvist, Kjell, Schabath, Matthew B., Andrew, Angeline, Duell, Eric, Melander, Olle, Brunnstrom, Hans, Lazarus, Philip, Arnold, Susanne, Slone, Stacey, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Landi, Maria Teresa, Amos, Christopher, I, Brennan, Paul, Ferreiro-Iglesias, Aida, Lesseur, Corina, McKay, James, Hung, Rayjean J., Han, Younghun, Zong, Xuchen, Christiani, David, Johansson, Mattias, Xiao, Xiangjun, Li, Yafang, Qian, David C., Ji, Xuemei, Liu, Geoffrey, Caporaso, Neil, Scelo, Ghislaine, Zaridze, David, Mukeriya, Anush, Kontic, Milica, Ognjanovic, Simona, Lissowska, Jolanta, Szolkowska, Malgorzata, Swiatkowska, Beata, Janout, Vladimir, Holcatova, Ivana, Bolca, Ciprian, Savic, Milan, Ognjanovic, Miodrag, Bojesen, Stig Egil, Wu, Xifeng, Albanes, Demetrios, Aldrich, Melinda C., Tardon, Adonina, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, Le Marchand, Loic, Rennert, Gadi, Chen, Chu, Doherty, Jennifer, Goodman, Gary, Bickeboeller, Heike, Wichmann, H-Erich, Risch, Angela, Rosenberger, Albert, Shen, Hongbing, Dai, Juncheng, Field, John K., Davies, Michael, Woll, Penella, Teare, M. Dawn, Kiemeney, Lambertus A., van der Heijden, Erik H. F. M., Yuan, Jian-Min, Hong, Yun-Chul, Haugen, Aage, Zienolddiny, Shanbeh, Lam, Stephen, Tsao, Ming-Sound, Johansson, Mikael, Grankvist, Kjell, Schabath, Matthew B., Andrew, Angeline, Duell, Eric, Melander, Olle, Brunnstrom, Hans, Lazarus, Philip, Arnold, Susanne, Slone, Stacey, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Landi, Maria Teresa, Amos, Christopher, I, and Brennan, Paul

Abstract

Lung cancer has several genetic associations identified within the major histocompatibility complex (MHC); although the basis for these associations remains elusive. Here, we analyze MHC genetic variation among 26,044 lung cancer patients and 20,836 controls densely genotyped across the MHC, using the Illumina Illumina OncoArray or Illumina 660W SNP microarray. We impute sequence variation in classical HLA genes, fine-map MHC associations for lung cancer risk with major histologies and compare results between ethnicities. Independent and novel associations within HLA genes are identified in Europeans including amino acids in the HLA-B*0801 peptide binding groove and an independent HLA-DQB1*06 loci group. In Asians, associations are driven by two independent HLA allele sets that both increase risk in HLA-DQB1*0401 and HLA-DRB1*0701; the latter better represented by the amino acid Ala-104. These results implicate several HLA-tumor peptide interactions as the major MHC factor modulating lung cancer susceptibility.

Published
2018
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7. Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk

Author

Ji, Xuemei, Bosse, Yohan, Landi, Maria Teresa, Gui, Jiang, Xiao, Xiangjun, Qian, David, Joubert, Philippe, Lamontagne, Maxime, Li, Yafang, Gorlov, Ivan, de Biasi, Mariella, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Wu, Xifeng, Mckay, James, Zong, Xuchen, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Shen, Hongbing, Hong, Yun-Chul, Yuan, Jian-Min, Bertazzi, Pier A., Pesatori, Angela C., Ye, Yuanqing, Diao, Nancy, Su, Li, Zhang, Ruyang, Brhane, Yonathan, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Dai, Juncheng, Hu, Zhibin, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Doherty, Jennifer, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Brueske, Irene, Manz, Judith, 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, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Koh, Woon-Puay, Gao, Yu-Tang, Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, Ma'en, Timens, Wim, Zhu, Bin, Song, Lei, Artigas, Maria Soler, Tobin, Martin D., Wain, Louise V., Gu, Fangyi, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Tyndale, Rachel F., Wei, Wei-Qi, Chanock, Stephen, Brennan, Paul, Amos, Christopher I., Ji, Xuemei, Bosse, Yohan, Landi, Maria Teresa, Gui, Jiang, Xiao, Xiangjun, Qian, David, Joubert, Philippe, Lamontagne, Maxime, Li, Yafang, Gorlov, Ivan, de Biasi, Mariella, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Wu, Xifeng, Mckay, James, Zong, Xuchen, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Shen, Hongbing, Hong, Yun-Chul, Yuan, Jian-Min, Bertazzi, Pier A., Pesatori, Angela C., Ye, Yuanqing, Diao, Nancy, Su, Li, Zhang, Ruyang, Brhane, Yonathan, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Dai, Juncheng, Hu, Zhibin, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Doherty, Jennifer, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Brueske, Irene, Manz, Judith, 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, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Koh, Woon-Puay, Gao, Yu-Tang, Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, Ma'en, Timens, Wim, Zhu, Bin, Song, Lei, Artigas, Maria Soler, Tobin, Martin D., Wain, Louise V., Gu, Fangyi, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Tyndale, Rachel F., Wei, Wei-Qi, Chanock, Stephen, Brennan, Paul, and Amos, Christopher I.

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.

Published
2018
Full Text
View/download PDF

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

Author

Ji, Xuemei, Bosse, Yohan, Landi, Maria Teresa, Gui, Jiang, Xiao, Xiangjun, Qian, David, Joubert, Philippe, Lamontagne, Maxime, Li, Yafang, Gorlov, Ivan, de Biasi, Mariella, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Wu, Xifeng, Mckay, James, Zong, Xuchen, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Shen, Hongbing, Hong, Yun-Chul, Yuan, Jian-Min, Bertazzi, Pier A., Pesatori, Angela C., Ye, Yuanqing, Diao, Nancy, Su, Li, Zhang, Ruyang, Brhane, Yonathan, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Dai, Juncheng, Hu, Zhibin, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Doherty, Jennifer, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Brueske, Irene, Manz, Judith, 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, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Koh, Woon-Puay, Gao, Yu-Tang, Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, Ma'en, Timens, Wim, Zhu, Bin, Song, Lei, Artigas, Maria Soler, Tobin, Martin D., Wain, Louise V., Gu, Fangyi, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Tyndale, Rachel F., Wei, Wei-Qi, Chanock, Stephen, Brennan, Paul, Amos, Christopher I., Ji, Xuemei, Bosse, Yohan, Landi, Maria Teresa, Gui, Jiang, Xiao, Xiangjun, Qian, David, Joubert, Philippe, Lamontagne, Maxime, Li, Yafang, Gorlov, Ivan, de Biasi, Mariella, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Wu, Xifeng, Mckay, James, Zong, Xuchen, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Shen, Hongbing, Hong, Yun-Chul, Yuan, Jian-Min, Bertazzi, Pier A., Pesatori, Angela C., Ye, Yuanqing, Diao, Nancy, Su, Li, Zhang, Ruyang, Brhane, Yonathan, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Dai, Juncheng, Hu, Zhibin, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Doherty, Jennifer, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Brueske, Irene, Manz, Judith, 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, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Koh, Woon-Puay, Gao, Yu-Tang, Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, Ma'en, Timens, Wim, Zhu, Bin, Song, Lei, Artigas, Maria Soler, Tobin, Martin D., Wain, Louise V., Gu, Fangyi, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Tyndale, Rachel F., Wei, Wei-Qi, Chanock, Stephen, Brennan, Paul, and Amos, Christopher I.

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.

Published
2018
Full Text
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9. Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population

Author

Li, Yafang, Xiao, Xiangjun, Han, Younghun, Gorlova, Olga, Qian, David, Leighl, Natasha, Johansen, Jakob S., Barnett, Matt, Chen, Chu, Goodman, Gary, Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, H-Erich, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, 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, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Houlston, Richard, Artigas, María Soler, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Liu, Geoffrey, Bojesen, Stig E., 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., Li, Yafang, Xiao, Xiangjun, Han, Younghun, Gorlova, Olga, Qian, David, Leighl, Natasha, Johansen, Jakob S., Barnett, Matt, Chen, Chu, Goodman, Gary, Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, H-Erich, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, 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, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Houlston, Richard, Artigas, María Soler, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Liu, Geoffrey, Bojesen, Stig E., 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., and Amos, Christopher I.

Abstract

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Both environmental and genetic risk factors contribute to lung carcinogenesis. We conducted a genome-wide interaction analysis between SNPs and smoking status (never vs ever smokers) in a European-descent population. We adopted a two-step analysis strategy in the discovery stage: we first conducted a case-only interaction analysis to assess the relationship between SNPs and smoking behavior using 13,336 NSCLC cases. Candidate SNPs with p-value less than 0.001 were further analyzed using a standard case-control interaction analysis including 13970 controls. The significant SNPs with p-value less than 3.5x10-5 (correcting for multiple tests) from the case-control analysis in the discovery stage were further validated using an independent replication dataset comprising 5377 controls and 3054 NSCLC cases. We further stratified the analysis by histological subtypes. Two novel SNPs, rs6441286 and rs17723637, were identified for overall lung cancer risk. The interaction odds ratio and meta-analysis p-value for these two SNPs were 1.24 with 6.96x10-7 and 1.37 with 3.49x10-7, respectively. Additionally, interaction of smoking with rs4751674 was identified in squamous cell lung carcinoma with an odds ratio of 0.58 and p-value of 8.12x10-7. This study is by far the largest genome-wide SNP-smoking interaction analysis reported for lung cancer. The three identified novel SNPs provide potential candidate biomarkers for lung cancer risk screening and intervention. The results from our study reinforce that gene-smoking interactions play important roles in the etiology of lung cancer and account for part of the missing heritability of this disease.

Published
2018
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10. Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity

Author

Ferreiro-Iglesias, Aida, Lesseur, Corina, McKay, James, Hung, Rayjean J., Han, Younghun, Zong, Xuchen, Christiani, David, Johansson, Mattias, Xiao, Xiangjun, Li, Yafang, Qian, David C., Ji, Xuemei, Liu, Geoffrey, Caporaso, Neil, Scelo, Ghislaine, Zaridze, David, Mukeriya, Anush, Kontic, Milica, Ognjanovic, Simona, Lissowska, Jolanta, Szolkowska, Malgorzata, Swiatkowska, Beata, Janout, Vladimir, Holcatova, Ivana, Bolca, Ciprian, Savic, Milan, Ognjanovic, Miodrag, Bojesen, Stig Egil, Wu, Xifeng, Albanes, Demetrios, Aldrich, Melinda C., Tardon, Adonina, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, Le Marchand, Loic, Rennert, Gadi, Chen, Chu, Doherty, Jennifer, Goodman, Gary, Bickeboeller, Heike, Wichmann, H-Erich, Risch, Angela, Rosenberger, Albert, Shen, Hongbing, Dai, Juncheng, Field, John K., Davies, Michael, Woll, Penella, Teare, M. Dawn, Kiemeney, Lambertus A., van der Heijden, Erik H. F. M., Yuan, Jian-Min, Hong, Yun-Chul, Haugen, Aage, Zienolddiny, Shanbeh, Lam, Stephen, Tsao, Ming-Sound, Johansson, Mikael, Grankvist, Kjell, Schabath, Matthew B., Andrew, Angeline, Duell, Eric, Melander, Olle, Brunnstrom, Hans, Lazarus, Philip, Arnold, Susanne, Slone, Stacey, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Landi, Maria Teresa, Amos, Christopher, I, Brennan, Paul, Ferreiro-Iglesias, Aida, Lesseur, Corina, McKay, James, Hung, Rayjean J., Han, Younghun, Zong, Xuchen, Christiani, David, Johansson, Mattias, Xiao, Xiangjun, Li, Yafang, Qian, David C., Ji, Xuemei, Liu, Geoffrey, Caporaso, Neil, Scelo, Ghislaine, Zaridze, David, Mukeriya, Anush, Kontic, Milica, Ognjanovic, Simona, Lissowska, Jolanta, Szolkowska, Malgorzata, Swiatkowska, Beata, Janout, Vladimir, Holcatova, Ivana, Bolca, Ciprian, Savic, Milan, Ognjanovic, Miodrag, Bojesen, Stig Egil, Wu, Xifeng, Albanes, Demetrios, Aldrich, Melinda C., Tardon, Adonina, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, Le Marchand, Loic, Rennert, Gadi, Chen, Chu, Doherty, Jennifer, Goodman, Gary, Bickeboeller, Heike, Wichmann, H-Erich, Risch, Angela, Rosenberger, Albert, Shen, Hongbing, Dai, Juncheng, Field, John K., Davies, Michael, Woll, Penella, Teare, M. Dawn, Kiemeney, Lambertus A., van der Heijden, Erik H. F. M., Yuan, Jian-Min, Hong, Yun-Chul, Haugen, Aage, Zienolddiny, Shanbeh, Lam, Stephen, Tsao, Ming-Sound, Johansson, Mikael, Grankvist, Kjell, Schabath, Matthew B., Andrew, Angeline, Duell, Eric, Melander, Olle, Brunnstrom, Hans, Lazarus, Philip, Arnold, Susanne, Slone, Stacey, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Landi, Maria Teresa, Amos, Christopher, I, and Brennan, Paul

Abstract

Lung cancer has several genetic associations identified within the major histocompatibility complex (MHC); although the basis for these associations remains elusive. Here, we analyze MHC genetic variation among 26,044 lung cancer patients and 20,836 controls densely genotyped across the MHC, using the Illumina Illumina OncoArray or Illumina 660W SNP microarray. We impute sequence variation in classical HLA genes, fine-map MHC associations for lung cancer risk with major histologies and compare results between ethnicities. Independent and novel associations within HLA genes are identified in Europeans including amino acids in the HLA-B*0801 peptide binding groove and an independent HLA-DQB1*06 loci group. In Asians, associations are driven by two independent HLA allele sets that both increase risk in HLA-DQB1*0401 and HLA-DRB1*0701; the latter better represented by the amino acid Ala-104. These results implicate several HLA-tumor peptide interactions as the major MHC factor modulating lung cancer susceptibility.

Published
2018
Full Text
View/download PDF

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

Author

Ji, Xuemei, Bosse, Yohan, Landi, Maria Teresa, Gui, Jiang, Xiao, Xiangjun, Qian, David, Joubert, Philippe, Lamontagne, Maxime, Li, Yafang, Gorlov, Ivan, de Biasi, Mariella, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Wu, Xifeng, Mckay, James, Zong, Xuchen, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Shen, Hongbing, Hong, Yun-Chul, Yuan, Jian-Min, Bertazzi, Pier A., Pesatori, Angela C., Ye, Yuanqing, Diao, Nancy, Su, Li, Zhang, Ruyang, Brhane, Yonathan, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Dai, Juncheng, Hu, Zhibin, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Doherty, Jennifer, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Brueske, Irene, Manz, Judith, 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, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Koh, Woon-Puay, Gao, Yu-Tang, Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, Ma'en, Timens, Wim, Zhu, Bin, Song, Lei, Artigas, Maria Soler, Tobin, Martin D., Wain, Louise V., Gu, Fangyi, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Tyndale, Rachel F., Wei, Wei-Qi, Chanock, Stephen, Brennan, Paul, Amos, Christopher I., Ji, Xuemei, Bosse, Yohan, Landi, Maria Teresa, Gui, Jiang, Xiao, Xiangjun, Qian, David, Joubert, Philippe, Lamontagne, Maxime, Li, Yafang, Gorlov, Ivan, de Biasi, Mariella, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Wu, Xifeng, Mckay, James, Zong, Xuchen, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Shen, Hongbing, Hong, Yun-Chul, Yuan, Jian-Min, Bertazzi, Pier A., Pesatori, Angela C., Ye, Yuanqing, Diao, Nancy, Su, Li, Zhang, Ruyang, Brhane, Yonathan, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Dai, Juncheng, Hu, Zhibin, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Doherty, Jennifer, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Brueske, Irene, Manz, Judith, 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, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Koh, Woon-Puay, Gao, Yu-Tang, Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, Ma'en, Timens, Wim, Zhu, Bin, Song, Lei, Artigas, Maria Soler, Tobin, Martin D., Wain, Louise V., Gu, Fangyi, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Tyndale, Rachel F., Wei, Wei-Qi, Chanock, Stephen, Brennan, Paul, and Amos, Christopher I.

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.

Published
2018
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12. Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity

Author

Ferreiro-Iglesias, Aida, Lesseur, Corina, McKay, James, Hung, Rayjean J., Han, Younghun, Zong, Xuchen, Christiani, David, Johansson, Mattias, Xiao, Xiangjun, Li, Yafang, Qian, David C., Ji, Xuemei, Liu, Geoffrey, Caporaso, Neil, Scelo, Ghislaine, Zaridze, David, Mukeriya, Anush, Kontic, Milica, Ognjanovic, Simona, Lissowska, Jolanta, Szolkowska, Malgorzata, Swiatkowska, Beata, Janout, Vladimir, Holcatova, Ivana, Bolca, Ciprian, Savic, Milan, Ognjanovic, Miodrag, Bojesen, Stig Egil, Wu, Xifeng, Albanes, Demetrios, Aldrich, Melinda C., Tardon, Adonina, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, Le Marchand, Loic, Rennert, Gadi, Chen, Chu, Doherty, Jennifer, Goodman, Gary, Bickeboeller, Heike, Wichmann, H-Erich, Risch, Angela, Rosenberger, Albert, Shen, Hongbing, Dai, Juncheng, Field, John K., Davies, Michael, Woll, Penella, Teare, M. Dawn, Kiemeney, Lambertus A., van der Heijden, Erik H. F. M., Yuan, Jian-Min, Hong, Yun-Chul, Haugen, Aage, Zienolddiny, Shanbeh, Lam, Stephen, Tsao, Ming-Sound, Johansson, Mikael, Grankvist, Kjell, Schabath, Matthew B., Andrew, Angeline, Duell, Eric, Melander, Olle, Brunnstrom, Hans, Lazarus, Philip, Arnold, Susanne, Slone, Stacey, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Landi, Maria Teresa, Amos, Christopher, I, Brennan, Paul, Ferreiro-Iglesias, Aida, Lesseur, Corina, McKay, James, Hung, Rayjean J., Han, Younghun, Zong, Xuchen, Christiani, David, Johansson, Mattias, Xiao, Xiangjun, Li, Yafang, Qian, David C., Ji, Xuemei, Liu, Geoffrey, Caporaso, Neil, Scelo, Ghislaine, Zaridze, David, Mukeriya, Anush, Kontic, Milica, Ognjanovic, Simona, Lissowska, Jolanta, Szolkowska, Malgorzata, Swiatkowska, Beata, Janout, Vladimir, Holcatova, Ivana, Bolca, Ciprian, Savic, Milan, Ognjanovic, Miodrag, Bojesen, Stig Egil, Wu, Xifeng, Albanes, Demetrios, Aldrich, Melinda C., Tardon, Adonina, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, Le Marchand, Loic, Rennert, Gadi, Chen, Chu, Doherty, Jennifer, Goodman, Gary, Bickeboeller, Heike, Wichmann, H-Erich, Risch, Angela, Rosenberger, Albert, Shen, Hongbing, Dai, Juncheng, Field, John K., Davies, Michael, Woll, Penella, Teare, M. Dawn, Kiemeney, Lambertus A., van der Heijden, Erik H. F. M., Yuan, Jian-Min, Hong, Yun-Chul, Haugen, Aage, Zienolddiny, Shanbeh, Lam, Stephen, Tsao, Ming-Sound, Johansson, Mikael, Grankvist, Kjell, Schabath, Matthew B., Andrew, Angeline, Duell, Eric, Melander, Olle, Brunnstrom, Hans, Lazarus, Philip, Arnold, Susanne, Slone, Stacey, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Landi, Maria Teresa, Amos, Christopher, I, and Brennan, Paul

Abstract

Lung cancer has several genetic associations identified within the major histocompatibility complex (MHC); although the basis for these associations remains elusive. Here, we analyze MHC genetic variation among 26,044 lung cancer patients and 20,836 controls densely genotyped across the MHC, using the Illumina Illumina OncoArray or Illumina 660W SNP microarray. We impute sequence variation in classical HLA genes, fine-map MHC associations for lung cancer risk with major histologies and compare results between ethnicities. Independent and novel associations within HLA genes are identified in Europeans including amino acids in the HLA-B*0801 peptide binding groove and an independent HLA-DQB1*06 loci group. In Asians, associations are driven by two independent HLA allele sets that both increase risk in HLA-DQB1*0401 and HLA-DRB1*0701; the latter better represented by the amino acid Ala-104. These results implicate several HLA-tumor peptide interactions as the major MHC factor modulating lung cancer susceptibility.

Published
2018
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13. Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk

Author

Ji, Xuemei, Bosse, Yohan, Landi, Maria Teresa, Gui, Jiang, Xiao, Xiangjun, Qian, David, Joubert, Philippe, Lamontagne, Maxime, Li, Yafang, Gorlov, Ivan, de Biasi, Mariella, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Wu, Xifeng, Mckay, James, Zong, Xuchen, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Shen, Hongbing, Hong, Yun-Chul, Yuan, Jian-Min, Bertazzi, Pier A., Pesatori, Angela C., Ye, Yuanqing, Diao, Nancy, Su, Li, Zhang, Ruyang, Brhane, Yonathan, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Dai, Juncheng, Hu, Zhibin, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Doherty, Jennifer, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Brueske, Irene, Manz, Judith, 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, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Koh, Woon-Puay, Gao, Yu-Tang, Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, Ma'en, Timens, Wim, Zhu, Bin, Song, Lei, Artigas, Maria Soler, Tobin, Martin D., Wain, Louise V., Gu, Fangyi, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Tyndale, Rachel F., Wei, Wei-Qi, Chanock, Stephen, Brennan, Paul, Amos, Christopher I., Ji, Xuemei, Bosse, Yohan, Landi, Maria Teresa, Gui, Jiang, Xiao, Xiangjun, Qian, David, Joubert, Philippe, Lamontagne, Maxime, Li, Yafang, Gorlov, Ivan, de Biasi, Mariella, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Wu, Xifeng, Mckay, James, Zong, Xuchen, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Shen, Hongbing, Hong, Yun-Chul, Yuan, Jian-Min, Bertazzi, Pier A., Pesatori, Angela C., Ye, Yuanqing, Diao, Nancy, Su, Li, Zhang, Ruyang, Brhane, Yonathan, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Dai, Juncheng, Hu, Zhibin, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Doherty, Jennifer, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Brueske, Irene, Manz, Judith, 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, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Koh, Woon-Puay, Gao, Yu-Tang, Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, Ma'en, Timens, Wim, Zhu, Bin, Song, Lei, Artigas, Maria Soler, Tobin, Martin D., Wain, Louise V., Gu, Fangyi, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Tyndale, Rachel F., Wei, Wei-Qi, Chanock, Stephen, Brennan, Paul, and Amos, Christopher I.

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.

Published
2018
Full Text
View/download PDF

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