Genes associated with genetic and rare lung diseases and the risk of lung cancer

We investigated whether markers, genes or terms of the Human Phenotype Ontology associated with genetic or rare diseases (GARDs) that affect airway or lung function are associated with lung cancer. Genes of interest were extracted from GARD (Genetic and Rare Diseases Information Center), OMIM (Online Mendelian Inheritance in Man®), ORPHANET and Monarch Initiative. Individual SNP, gene level and gene-set analyses were performed for 52,207 SNPs, 1,677 genes or for 620 terms of the Human Phenotype Ontology. The analysis included 14,068 lung cancer cases and 12,390 cancer-free control subjects of European descent from the International Lung Cancer Consortium ILCCO. The marker rs56113850 (OR=0.893, 95%CI: 0.862-0.924) was associated with lung cancer (p=1.2x10-10). This marker is located in CYP2A6 as well as in an enhancer region of LTBP4, which is associated with cutis laxa. A suggestive significant association was observed for two markers associated with the DMD gene, which is linked to Duchenne muscular dystrophy. The gene sets "Abnormal circulating adrenocorticotropin concentration" and "Central nervous system neoplasm" were found to be significantly enriched with GARD genes, and can therefore be considered to be associated with lung cancer. Genes associated with genetic and rare lung diseases do not generally appear to carry risk factors for lung cancer. However, genes associated with the hypothalamic-pituitary-adrenal axis show some, but rather weak or complex, associations with lung cancer. Tests at the gene level provide extremely inhomogeneous results, even when applied to the same data.

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Publication Details

Journal
BMC Cancer
Published
2026-04-01
DOI
https://doi.org/10.1186/s12885-026-15934-2
Primary Topic
Genomics and Rare Diseases
Type
article
Field-Weighted Citation Impact
0.00

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article

Genes associated with genetic and rare lung diseases and the risk of lung cancer

Gary E. Goodman, Penella J. Woll, Shanbeh Zienolddiny, Angela Cox et al.
BMC Cancer
Genomics and Rare Diseases
article

Genes associated with genetic and rare lung diseases and the risk of lung cancer

Gary E. Goodman, Penella J. Woll, Shanbeh Zienolddiny, Angela Cox, Angeline S. Andrew, Melinda C. Aldrich, Albert Rosenberger, Angela Risch, Susanne M. Arnold, Michael P.A. Davies, R. Hung, L. A. Kiemeney, Heike Bickeböller, Stig E. Bojesen, Jennifer A. Doherty, Philip Lazarus, N Caporaso, Demetrios Albanes, Loïc Le Marchand, David C. Christiani, Geoffrey Liu, Guillermo Fernández‐Tardón, Gad Rennert, John K. Field, Paul Brennan, Adonina Tardon, Sanjay S. Shete, Christopher I. Amos, Maria Teresa Landi, Stephen Lam, Fiona Taylor, Matthew B. Schabath
article en

Abstract

We investigated whether markers, genes or terms of the Human Phenotype Ontology associated with genetic or rare diseases (GARDs) that affect airway or lung function are associated with lung cancer. Genes of interest were extracted from GARD (Genetic and Rare Diseases Information Center), OMIM (Online Mendelian Inheritance in Man®), ORPHANET and Monarch Initiative. Individual SNP, gene level and gene-set analyses were performed for 52,207 SNPs, 1,677 genes or for 620 terms of the Human Phenotype Ontology. The analysis included 14,068 lung cancer cases and 12,390 cancer-free control subjects of European descent from the International Lung Cancer Consortium ILCCO. The marker rs56113850 (OR=0.893, 95%CI: 0.862-0.924) was associated with lung cancer (p=1.2x10-10). This marker is located in CYP2A6 as well as in an enhancer region of LTBP4, which is associated with cutis laxa. A suggestive significant association was observed for two markers associated with the DMD gene, which is linked to Duchenne muscular dystrophy. The gene sets "Abnormal circulating adrenocorticotropin concentration" and "Central nervous system neoplasm" were found to be significantly enriched with GARD genes, and can therefore be considered to be associated with lung cancer. Genes associated with genetic and rare lung diseases do not generally appear to carry risk factors for lung cancer. However, genes associated with the hypothalamic-pituitary-adrenal axis show some, but rather weak or complex, associations with lung cancer. Tests at the gene level provide extremely inhomogeneous results, even when applied to the same data.

BMC CancerVol. 26(1)
Dartmouth College (US), University of Hawaiʻi at Mānoa (US), University of Copenhagen (DK), National Institutes of Health (US), University of Hawaii System (US), National Institute of Occupational Health (NO), The University of Texas MD Anderson Cancer Center (US), Harvard University (US), University of British Columbia (CA), University of Kentucky (US), Radboud University Nijmegen (NL), University of Liverpool (GB), University of New Mexico (US), Washington State University Spokane (US), University of Salzburg (AT), University of Toronto (CA), Lunenfeld-Tanenbaum Research Institute (CA), University of Utah (US), Huntsman Cancer Institute (US), Roy Castle Lung Cancer Foundation (GB), Markey Cancer Center (US), Gentofte Hospital (DK), Princess Margaret Cancer Centre (CA), Radboud University Medical Center (NL), Moffitt Cancer Center (US), Massachusetts General Hospital (US), Swedish Medical Center (US), Cancer Center of Hawaii (US), Carmel Medical Center (IL), Public Health Ontario (CA), Sinai Health System (CA), National Cancer Institute (US), New Mexico Cancer Center (US), Duro Felguera (Spain) (ES), Centre international de recherche sur le cancer (FR), University of Hawaii Cancer Center, UNM Comprehensive Cancer Center, University of Göttingen (DE), Vanderbilt University Medical Center (US), Umeå University (SE), University of Sheffield (GB)
Georg-August-Universität Göttingen
Good health and well-being
Openalex Percentile: Top 28%
Genomics and Rare Diseases
DOIOpen Access PDFOpenAlex
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