Association Analysis of Driver Gene-Related Genetic Variants Identified Novel Lung Cancer Susceptibility Loci with 20,871 Lung Cancer Cases and 15,971 Controls

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Association Analysis of Driver Gene-Related Genetic Variants Identified Novel Lung Cancer Susceptibility Loci with 20,871 Lung Cancer Cases and 15,971 Controls

Wang, Yuzhuo (author): Nanjing Medical University,Jiangsu Cancer Hospital

Gorlova, Olga Y. (author): Dartmouth College,Baylor College of Medicine

Gorlov, Ivan P. (author): Baylor College of Medicine,Dartmouth College

Zhu, Meng (author): Jiangsu Cancer Hospital,Nanjing Medical University

Dai, Juncheng (author): Nanjing Medical University

Albanes, Demetrius (author): National Cancer Institute, USA

Lam, Stephen (author): British Columbia Cancer Agency

Tardon, Adonina (author): University of Oviedo

Chen, Chu (author): Fred Hutchinson Cancer Research Center,Harvard University,Vanderbilt University

Goodman, Gary E. (author): Swedish Medical Center

Bojesen, Stig E. (author): University of Copenhagen,Copenhagen University Hospital

Landi, Maria Teresa (author): National Cancer Institute, USA

Johansson, Mattias (author): International Agency for Research on Cancer, World Health Organization

Risch, Angela (author): German Center for Lung Research (DZL),University of Salzburg,German Cancer Research Centre

Wichmann, Heunz-Erich (author): Technical University of Munich,Helmholtz Zentrum München,Ludwig-Maximilian University of Munich

Bickeboller, Heike (author): University Medical Center Göttingen

Christiani, David C. (author)

Rennert, Gad (author): Technion - Israel Institute of Technology

Arnold, Susanne M. (author): University of Kentucky

Brennan, Paul (author): International Agency for Research on Cancer, World Health Organization

Field, John K. (author): University of Liverpool

Shete, Sanjay (author): University of Texas MD Anderson Cancer Center,Dartmouth-Hitchcock Medical Center

Le Marchand, Loic (author): University of Hawai'i at Hilo

Melander, Olle (author): Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups,Skåne University Hospital

Brunnstrom, Hans (author): Lund University,Lunds universitet,Förbättrad diagnostik och prognostik vid lungcancer och metastaser till lunga,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Improved diagnostics and prognostics of lung cancer and metastases to the lungs,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments

Liu, Geoffrey (author): Princess Margaret Hospital University of Toronto

Hung, Rayjean J. (author): Sinai Health System

Andrew, Angeline S. (author)

Kiemeney, Lambertus A. (author): Radboud University Medical Center

Zienolddiny, Shanbeh (author): National Institute of Occupational Health, Norway

Grankvist, Kjell (author): Umeå University,Umeå universitet,Klinisk kemi

Johansson, Mikael (author): Umeå University,Umeå universitet,Onkologi

Caporaso, Neil E. (author): National Cancer Institute, USA

Woll, Penella J. (author): University of Sheffield

Lazarus, Philip (author): Washington State University

Schabath, Matthew B. (author): H. Lee Moffitt Cancer Center & Research Institute

Aldrich, Melinda C. (author)

Stevens, Victoria L. (author): American Cancer Society

Ma, Hongxia (author): Nanjing Medical University

Jin, Guangfu (author): Nanjing Medical University

Hu, Zhibin (author): Nanjing Medical University

Amos, Christopher I. (author): Baylor College of Medicine

Shen, Hongbing (author): Nanjing Medical University

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(creator_code:org_t)

American Association for Cancer Research, 2020
2020
English.
In: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 29:7, s. 1423-1429

Related links:: http://dx.doi.org/10...; show more...; https://urn.kb.se/re...; https://doi.org/10.1...; https://lup.lub.lu.s...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

Background: A substantial proportion of cancer driver genes (CDG) are also cancer predisposition genes. However, the associations between genetic variants in lung CDGs and the susceptibility to lung cancer have rarely been investigated.Methods: We selected expression-related single-nucleotide polymorphisms (eSNP) and nonsynonymous variants of lung CDGs, and tested their associations with lung cancer risk in two large-scale genome-wide association studies (20,871 cases and 15,971 controls of European descent). Conditional and joint association analysis was performed to identify independent risk variants. The associations of independent risk variants with somatic alterations in lung CDGs or recurrently altered pathways were investigated using data from The Cancer Genome Atlas (TCGA) project.Results: We identified seven independent SNPs in five lung CDGs that were consistently associated with lung cancer risk in discovery (P < 0.001) and validation (P < 0.05) stages. Among these loci, rs78062588 in TPM3 (1q21.3) was a new lung cancer susceptibility locus (OR = 0.86, P = 1.65 x 10(-6)). Subgroup analysis by histologic types further identified nine lung CDGs. Analysis of somatic alterations found that in lung adenocarcinomas, rs78062588[C] allele (TPM3 in 1q21.3) was associated with elevated somatic copy number of TPM3 (OR = 1.16, P = 0.02). In lung adenocarcinomas, rs1611182 (HLA-A in 6p22.1) was associated with truncation mutations of the transcriptional misregulation in cancer pathway (OR = 0.66, P = 1.76 x 10(-3)).Conclusions: Genetic variants can regulate functions of lung CDGs and influence lung cancer susceptibility. Impact: Our findings might help unravel biological mechanisms underlying lung cancer susceptibility.

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By the author/editor: Wang, Yuzhuo; Gorlova, Olga Y.; Gorlov, Ivan P.; Zhu, Meng; Dai, Juncheng; Albanes, Demetri ...; show more...; Lam, Stephen; Tardon, Adonina; Chen, Chu; Goodman, Gary E.; Bojesen, Stig E.; Landi, Maria Ter ...; Johansson, Matti ...; Risch, Angela; Wichmann, Heunz- ...; Bickeboller, Hei ...; Christiani, Davi ...; Rennert, Gad; Arnold, Susanne ...; Brennan, Paul; Field, John K.; Shete, Sanjay; Le Marchand, Loi ...; Melander, Olle; Brunnstrom, Hans; Liu, Geoffrey; Hung, Rayjean J.; Andrew, Angeline ...; Kiemeney, Lamber ...; Zienolddiny, Sha ...; Grankvist, Kjell; Johansson, Mikae ...; Caporaso, Neil E ...; Woll, Penella J.; Lazarus, Philip; Schabath, Matthe ...; Aldrich, Melinda ...; Stevens, Victori ...; Ma, Hongxia; Jin, Guangfu; Hu, Zhibin; Amos, Christophe ...; Shen, Hongbing; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

Articles in the publication: Cancer Epidemiol ...

By the university: Umeå University; Lund University

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Association Analysis of Driver Gene-Related Genetic Variants Identified Novel Lung Cancer Susceptibility Loci with 20,871 Lung Cancer Cases and 15,971 Controls

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