Individual and cumulative effects of GWAS susceptibility loci in lung cancer: associations after sub-phenotyping for COPD.

Epidemiological studies show that approximately 20-30% of chronic smokers develop chronic obstructive pulmonary disease (COPD) while 10-15% develop lung cancer. COPD pre-exists lung cancer in 50-90% of cases and has a heritability of 40-77%, much greater than for lung cancer with heritability of 15-...

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Autores principales:	Robert P Young, Raewyn J Hopkins, Chris F Whittington, Bryan A Hay, Michael J Epton, Gregory D Gamble
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d6ae38b81482452797811e4c240f763a
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spelling	oai:doaj.org-article:d6ae38b81482452797811e4c240f763a2021-11-18T06:59:15ZIndividual and cumulative effects of GWAS susceptibility loci in lung cancer: associations after sub-phenotyping for COPD.1932-620310.1371/journal.pone.0016476https://doaj.org/article/d6ae38b81482452797811e4c240f763a2011-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21304900/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Epidemiological studies show that approximately 20-30% of chronic smokers develop chronic obstructive pulmonary disease (COPD) while 10-15% develop lung cancer. COPD pre-exists lung cancer in 50-90% of cases and has a heritability of 40-77%, much greater than for lung cancer with heritability of 15-25%. These data suggest that smokers susceptible to COPD may also be susceptible to lung cancer. This study examines the association of several overlapping chromosomal loci, recently implicated by GWA studies in COPD, lung function and lung cancer, in (n = 1400) subjects sub-phenotyped for the presence of COPD and matched for smoking exposure. Using this approach we show; the 15q25 locus confers susceptibility to lung cancer and COPD, the 4q31 and 4q22 loci both confer a reduced risk to both COPD and lung cancer, the 6p21 locus confers susceptibility to lung cancer in smokers with pre-existing COPD, the 5p15 and 1q23 loci both confer susceptibility to lung cancer in those with no pre-existing COPD. We also show the 5q33 locus, previously associated with reduced FEV(1), appears to confer susceptibility to both COPD and lung cancer. The 6p21 locus previously linked to reduced FEV(1) is associated with COPD only. Larger studies will be needed to distinguish whether these COPD-related effects may reflect, in part, associations specific to different lung cancer histology. We demonstrate that when the "risk genotypes" derived from the univariate analysis are incorporated into an algorithm with clinical variables, independently associated with lung cancer in multivariate analysis, modest discrimination is possible on receiver operator curve analysis (AUC = 0.70). We suggest that genetic susceptibility to lung cancer includes genes conferring susceptibility to COPD and that sub-phenotyping with spirometry is critical to identifying genes underlying the development of lung cancer.Robert P YoungRaewyn J HopkinsChris F WhittingtonBryan A HayMichael J EptonGregory D GamblePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 2, p e16476 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Robert P Young Raewyn J Hopkins Chris F Whittington Bryan A Hay Michael J Epton Gregory D Gamble Individual and cumulative effects of GWAS susceptibility loci in lung cancer: associations after sub-phenotyping for COPD.
description	Epidemiological studies show that approximately 20-30% of chronic smokers develop chronic obstructive pulmonary disease (COPD) while 10-15% develop lung cancer. COPD pre-exists lung cancer in 50-90% of cases and has a heritability of 40-77%, much greater than for lung cancer with heritability of 15-25%. These data suggest that smokers susceptible to COPD may also be susceptible to lung cancer. This study examines the association of several overlapping chromosomal loci, recently implicated by GWA studies in COPD, lung function and lung cancer, in (n = 1400) subjects sub-phenotyped for the presence of COPD and matched for smoking exposure. Using this approach we show; the 15q25 locus confers susceptibility to lung cancer and COPD, the 4q31 and 4q22 loci both confer a reduced risk to both COPD and lung cancer, the 6p21 locus confers susceptibility to lung cancer in smokers with pre-existing COPD, the 5p15 and 1q23 loci both confer susceptibility to lung cancer in those with no pre-existing COPD. We also show the 5q33 locus, previously associated with reduced FEV(1), appears to confer susceptibility to both COPD and lung cancer. The 6p21 locus previously linked to reduced FEV(1) is associated with COPD only. Larger studies will be needed to distinguish whether these COPD-related effects may reflect, in part, associations specific to different lung cancer histology. We demonstrate that when the "risk genotypes" derived from the univariate analysis are incorporated into an algorithm with clinical variables, independently associated with lung cancer in multivariate analysis, modest discrimination is possible on receiver operator curve analysis (AUC = 0.70). We suggest that genetic susceptibility to lung cancer includes genes conferring susceptibility to COPD and that sub-phenotyping with spirometry is critical to identifying genes underlying the development of lung cancer.
format	article
author	Robert P Young Raewyn J Hopkins Chris F Whittington Bryan A Hay Michael J Epton Gregory D Gamble
author_facet	Robert P Young Raewyn J Hopkins Chris F Whittington Bryan A Hay Michael J Epton Gregory D Gamble
author_sort	Robert P Young
title	Individual and cumulative effects of GWAS susceptibility loci in lung cancer: associations after sub-phenotyping for COPD.
title_short	Individual and cumulative effects of GWAS susceptibility loci in lung cancer: associations after sub-phenotyping for COPD.
title_full	Individual and cumulative effects of GWAS susceptibility loci in lung cancer: associations after sub-phenotyping for COPD.
title_fullStr	Individual and cumulative effects of GWAS susceptibility loci in lung cancer: associations after sub-phenotyping for COPD.
title_full_unstemmed	Individual and cumulative effects of GWAS susceptibility loci in lung cancer: associations after sub-phenotyping for COPD.
title_sort	individual and cumulative effects of gwas susceptibility loci in lung cancer: associations after sub-phenotyping for copd.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/d6ae38b81482452797811e4c240f763a
work_keys_str_mv	AT robertpyoung individualandcumulativeeffectsofgwassusceptibilitylociinlungcancerassociationsaftersubphenotypingforcopd AT raewynjhopkins individualandcumulativeeffectsofgwassusceptibilitylociinlungcancerassociationsaftersubphenotypingforcopd AT chrisfwhittington individualandcumulativeeffectsofgwassusceptibilitylociinlungcancerassociationsaftersubphenotypingforcopd AT bryanahay individualandcumulativeeffectsofgwassusceptibilitylociinlungcancerassociationsaftersubphenotypingforcopd AT michaeljepton individualandcumulativeeffectsofgwassusceptibilitylociinlungcancerassociationsaftersubphenotypingforcopd AT gregorydgamble individualandcumulativeeffectsofgwassusceptibilitylociinlungcancerassociationsaftersubphenotypingforcopd
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Individual and cumulative effects of GWAS susceptibility loci in lung cancer: associations after sub-phenotyping for COPD.

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