Candidate pathway analysis of surfactant proteins identifies CTSH and SFTA2 that influences lung cancer risk

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Candidate pathway analysis of surfactant proteins identifies CTSH and SFTA2 that influences lung cancer risk

Luyapan, Jennifer (författare): Quantitative Biomedical Science Program, Geisel School of Medicine, Dartmouth College, Hanover, United States; Department of Biomedical Data Science, Geisel School of Medicine, Dartmouth College, United States

Bossé, Yohan (författare): Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec City, Canada; Department of Molecular Medicine, Laval University, Quebec City, Canada

Li, Zhonglin (författare): Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec City, Canada

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Xiao, Xiangjun (författare): Department of Medicine, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, United States

Rosenberger, Albert (författare): Institut für Genetische Epidemiologie, Georg-August-Universität Göttingen, Niedersachsen, Gottingen, Germany

Hung, Rayjean J. (författare): Prosserman Centre for Population Health Research, Lunenfeld-Tanenbuaum Research Institute, Sinai Health System, ON, Toronto, Canada

Lam, Stephen (författare): Department of Integrative Oncology, British Columbia Cancer Agency, BC, Vancouver, Canada

Zienolddiny, Shanbeh (författare): Department of Toxicology, National Institute of Occupational Health, Oslo, Norway

Liu, Geoffrey (författare): Princess Margaret Cancer Centre, Princess Margaret Research Institute, Epidemiology Division, ON, Toronto, Canada

Kiemeney, Lambertus A. (författare): Department for Health Evidence, Radboud University Medical Center, Nijmegen, Netherlands

Chen, Chu (författare): Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Center, WA, Seattle, United States

McKay, James (författare): International Agency for Research on Cancer (IARC/WHO), Genomic Epidemiology Branch Lyon 69008, France

Johansson, Mattias (författare): International Agency for Research on Cancer (IARC/WHO), Genomic Epidemiology Branch Lyon 69008, France

Johansson, Mikael (författare): Umeå universitet,Onkologi

Tardon, Adonina (författare): Health Research Institute of the Principality of Asturias, University of Oviedo and CIBERSP, Asturias, Oviedo, Spain

Fernandez-Tardon, Guillermo (författare): Health Research Institute of the Principality of Asturias, University of Oviedo and CIBERSP, Asturias, Oviedo, Spain

Brennan, Paul (författare): Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig Maximillians University, Bavaria, Munich, Germany

Field, John K. (författare): Molecular and Clinical Cancer Medicine, Roy Castle Lung Cancer Research Programme, University of Liverpool Institute of Translational Medicine, Liverpool, United Kingdom

Davies, Michael P. (författare): Molecular and Clinical Cancer Medicine, Roy Castle Lung Cancer Research Programme, University of Liverpool Institute of Translational Medicine, Liverpool, United Kingdom

Woll, Penella J. (författare): Academic Unit of Clinical Oncology, University of Sheffield, Sheffield, United Kingdom

Cox, Angela (författare): Department of Oncology and Metabolism, University of Sheffield, Sheffield, United Kingdom

Taylor, Fiona (författare): Department of Oncology and Metabolism, University of Sheffield, Sheffield, United Kingdom

Arnold, Susanne M. (författare): Division of Medical Oncology, Cancer Center, University of Kentucky, Lexington, United States

Lazarus, Philip (författare): Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, WA, Spokane, United States

Grankvist, Kjell (författare): Umeå universitet,Klinisk kemi

Landi, Maria T. (författare): Division of Cancer Epidemiology and Genetics, National Cancer Institute, MD, Bethesda, United States

Christiani, David C. (författare): Department of Environmental Health, Harvard School of Public Health, Boston, United States; Department of Medicine, Massachusetts General Hospital, Boston, United States

MacKenzie, Todd A. (författare): Quantitative Biomedical Science Program, Geisel School of Medicine, Dartmouth College, Hanover, United States; Department of Biomedical Data Science, Geisel School of Medicine, Dartmouth College, United States

Amos, Christopher I. (författare): Quantitative Biomedical Science Program, Geisel School of Medicine, Dartmouth College, Hanover, United States; Department of Biomedical Data Science, Geisel School of Medicine, Dartmouth College, United States; Department of Medicine, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, United States

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Oxford University Press, 2023
2023
Engelska.
Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 32:18, s. 2842-2855

Relaterad länk:: https://urn.kb.se/re...; visa fler...; https://doi.org/10.1...; visa färre...

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Pulmonary surfactant is a lipoprotein synthesized and secreted by alveolar type II cells in lung. We evaluated the associations between 200,139 single nucleotide polymorphisms (SNPs) of 40 surfactant-related genes and lung cancer risk using genotyped data from two independent lung cancer genome-wide association studies. Discovery data included 18,082 cases and 13,780 controls of European ancestry. Replication data included 1,914 cases and 3,065 controls of European descent. Using multivariate logistic regression, we found novel SNPs in surfactant-related genes CTSH [rs34577742 C > T, odds ratio (OR) = 0.90, 95% confidence interval (CI) = 0.89-0.93, P = 7.64 × 10-9] and SFTA2 (rs3095153 G > A, OR = 1.16, 95% CI = 1.10-1.21, P = 1.27 × 10-9) associated with overall lung cancer in the discovery data and validated in an independent replication data-CTSH (rs34577742 C > T, OR = 0.88, 95% CI = 0.80-0.96, P = 5.76 × 10-3) and SFTA2 (rs3095153 G > A, OR = 1.14, 95% CI = 1.01-1.28, P = 3.25 × 10-2). Among ever smokers, we found SNPs in CTSH (rs34577742 C > T, OR = 0.89, 95% CI = 0.85-0.92, P = 1.94 × 10-7) and SFTA2 (rs3095152 G > A, OR = 1.20, 95% CI = 1.14-1.27, P = 4.25 × 10-11) associated with overall lung cancer in the discovery data and validated in the replication data-CTSH (rs34577742 C > T, OR = 0.88, 95% CI = 0.79-0.97, P = 1.64 × 10-2) and SFTA2 (rs3095152 G > A, OR = 1.15, 95% CI = 1.01-1.30, P = 3.81 × 10-2). Subsequent transcriptome-wide association study using expression weights from a lung expression quantitative trait loci study revealed genes most strongly associated with lung cancer are CTSH (PTWAS = 2.44 × 10-4) and SFTA2 (PTWAS = 2.32 × 10-6).

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Candidate pathway analysis of surfactant proteins identifies CTSH and SFTA2 that influences lung cancer risk

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