Genetic Variation and Recurrent Haplotypes on Chromosome 6q23-25 Risk Locus in Familial Lung Cancer
Year: 2021
Type: article
Study design: Observational Study
Abstract: Although lung cancer is known to be caused by environmental factors, it has also been shown to have genetic components, and the genetic etiology of lung cancer remains understudied. We previously identified a lung cancer risk locus on 6q23-25 using microsatellite data in families with a history of lung cancer. To further elucidate that signal, we performed targeted sequencing on nine of our most strongly linked families. Two-point linkage analysis of the sequencing data revealed that the signal was heterogeneous and that different families likely had different risk variants. Three specific haplotypes were shared by some of the families: 6q25.3-26 in families 42 and 44, 6q25.2-25.3 in families 47 and 59, and 6q24.2-25.1 in families 30, 33, and 35. Region-based logarithm of the odds scores and expression data identified the likely candidate genes for each haplotype overlap: ARID1B at 6q25.3, MAP3K4 at 6q26, and UTRN (6q24.1) and PHACTR2 (6q24.2). Further annotation was used to zero in on potential risk variants in those genes. All four genes are good candidate genes for lung cancer risk, having been linked to either lung cancer specifically or other cancers. However, this is the first time any of these genes has been implicated in germline risk. Functional analysis of these four genes is planned for future work. Significance: This study identifies four genes associated with lung cancer risk, which could help guide future lung cancer prevention and treatment approaches.
Source: Cancer Research
Authors: Anthony M. Musolf, Claire L. Simpson, Bilal A. Moiz, Claudio W. Pikielny, Candace D. Middlebrooks, Diptasri Mandal, Mariza de Andrade, Michael D. Cole, Colette Gaba, Ping Yang, Ming You, Yafang Li, Elena Y. Kupert, Marshall W. Anderson, Ann G. Schwartz, Susan M. Pinney, Christopher I. Amos, Joan E. Bailey-Wilson
Institutions: National Institutes of Health, National Human Genome Research Institute, University of Tennessee Health Science Center, Dartmouth College, Louisiana State University, Louisiana State University Health Sciences Center New Orleans, Mayo Clinic, University of Toledo, Mayo Clinic in Arizona, Medical College of Wisconsin, Baylor College of Medicine, Wayne State University, The Barbara Ann Karmanos Cancer Institute, University of Cincinnati
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: U.S. Department of Health and Human Services, Cancer Prevention and Research Institute of Texas, National Institutes of Health, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Cancer Institute, National Institute of Environmental Health Sciences
Awards: G1026249616, Recruitment of Established Investigators, G2420381388, Alpha-1 AD Carriers and Lung Cancer Risk, G316775309, Genetic Epidemiology of Lung Cancer, Fernald Community Cohort: Research Resource for Environmental Epidemiology, Center for Environmental Genetics, Sequencing Familial Lung Cancer, G4573876698, G477050727, Genetic Epidemiology of Cancer, Genetic Determinants of Lung Cancer Survival, G6458097836, DEVELOPMENT OF LUNG CANCER EPIDEMIOLOGY RESEARCH, G7263408359, G9000254095, Baylor College of Medicine Cancer Center - Cancer Center Support Grant, CANCER CENTER SUPPORT GRANT
OpenAlex ID: W3153633985