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Large-scale cross-cancer fine-mapping of the 5p15.33 region reveals multiple independent signals
H. Chen, A. Majumdar, L. Wang, S. Kar, KM. Brown, H. Feng, C. Turman, J. Dennis, D. Easton, K. Michailidou, J. Simard, Breast Cancer Association Consortium (BCAC), T. Bishop, IC. Cheng, JR. Huyghe, SL. Schmit, Colorectal Transdisciplinary Study...
Status minimální Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články
Grantová podpora
R01 CA139020
NCI NIH HHS - United States
P30 ES010126
NIEHS NIH HHS - United States
U19 CA203654
NCI NIH HHS - United States
UG1 CA189974
NCI NIH HHS - United States
U01 CA137088
NCI NIH HHS - United States
U19 CA148537
NCI NIH HHS - United States
R01 CA201407
NCI NIH HHS - United States
U19 CA148112
NCI NIH HHS - United States
R01 CA154823
NCI NIH HHS - United States
U19 CA148065
NCI NIH HHS - United States
P50 CA127001
NCI NIH HHS - United States
R03 CA123546
NCI NIH HHS - United States
R01 CA059045
NCI NIH HHS - United States
U19 CA148127
NCI NIH HHS - United States
U10 CA037429
NCI NIH HHS - United States
U01 CA182883
NCI NIH HHS - United States
R01 CA134958
NCI NIH HHS - United States
U01 CA194393
NCI NIH HHS - United States
P50 CA062924
NCI NIH HHS - United States
R01 CA244588
NCI NIH HHS - United States
R21 CA182821
NCI NIH HHS - United States
19167
Cancer Research UK - United Kingdom
U01 CA167551
NCI NIH HHS - United States
UM1 CA182883
NCI NIH HHS - United States
001
World Health Organization - International
16561
Cancer Research UK - United Kingdom
U01 CA247283
NCI NIH HHS - United States
NV18-03-00199
MZ0
CEP - Centrální evidence projektů
NLK
Directory of Open Access Journals
od 2020
PubMed Central
od 2020
ROAD: Directory of Open Access Scholarly Resources
od 2020
- Publikační typ
- časopisecké články MeSH
Genome-wide association studies (GWASs) have identified thousands of cancer risk loci revealing many risk regions shared across multiple cancers. Characterizing the cross-cancer shared genetic basis can increase our understanding of global mechanisms of cancer development. In this study, we collected GWAS summary statistics based on up to 375,468 cancer cases and 530,521 controls for fourteen types of cancer, including breast (overall, estrogen receptor [ER]-positive, and ER-negative), colorectal, endometrial, esophageal, glioma, head/neck, lung, melanoma, ovarian, pancreatic, prostate, and renal cancer, to characterize the shared genetic basis of cancer risk. We identified thirteen pairs of cancers with statistically significant local genetic correlations across eight distinct genomic regions. Specifically, the 5p15.33 region, harboring the TERT and CLPTM1L genes, showed statistically significant local genetic correlations for multiple cancer pairs. We conducted a cross-cancer fine-mapping of the 5p15.33 region based on eight cancers that showed genome-wide significant associations in this region (ER-negative breast, colorectal, glioma, lung, melanoma, ovarian, pancreatic, and prostate cancer). We used an iterative analysis pipeline implementing a subset-based meta-analysis approach based on cancer-specific conditional analyses and identified ten independent cross-cancer associations within this region. For each signal, we conducted cross-cancer fine-mapping to prioritize the most plausible causal variants. Our findings provide a more in-depth understanding of the shared inherited basis across human cancers and expand our knowledge of the 5p15.33 region in carcinogenesis.
Biostatistics Unit The Cyprus Institute of Neurology and Genetics Nicosia Cyprus
Bristol Dental School University of Bristol Bristol UK
Cancer Genetics Unit Royal Marsden NHS Foundation Trust London UK
Center for Human Genetics University Hospital of Marburg Marburg Germany
College of Medicine and Health Sciences United Arab Emirates University Al Ain Abu Dhabi UAE
Comprehensive Clinical Trials Unit University College London London UK
Cyprus School of Molecular Medicine Nicosia Cyprus
Department of Biostatistics Harvard T H Chan School of Public Health Boston MA USA
Department of Environmental and Occupational Health Sciences University of Washington Seattle WA USA
Department of Environmental Health Harvard T H Chan School of Public Health Boston MA USA
Department of Epidemiology and Biostatistics Case Western Reserve University Cleveland OH USA
Department of Epidemiology and Population Health Stanford University Palo Alto CA USA
Department of Epidemiology Harvard T H Chan School of Public Health Boston MA USA
Department of Epidemiology University of Washington Seattle WA USA
Department of Health Science Research Mayo Clinic Rochester MN USA
Department of Mathematics Indian Institute of Technology Hyderabad Kandi Telangana India
Department of Medical Oncology Dana Farber Harvard Cancer Center Boston MA USA
Department of Oncology University of Cambridge Cambridge UK
Department of Preventive Medicine University of Southern California Los Angeles CA USA
Department of Radiation Sciences Umeå University Umeå Sweden
Division of Genetics and Epidemiology The Institute of Cancer Research London UK
Genomic Medicine Institute Lerner Research Institute Cleveland Clinic Cleveland OH USA
Institute for Clinical and Translational Research Baylor College of Medicine Houston TX USA
International Agency for Research on Cancer World Health Organization Lyon France
Leeds Institute for Data Analytics University of Leeds Leeds UK
Leeds Institute of Cancer and Pathology University of Leeds Leeds UK
Oncogenetics Team Division of Genetics and Epidemiology The Institute of Cancer Research London UK
Public Health Sciences Division Fred Hutchinson Cancer Research Center Seattle WA USA
Seidman Cancer Center University Hospitals Cleveland OH USA
Statistical Genetics QIMR Berghofer Medical Research Institute Brisbane Australia
UNC Lineberger Comprehensive Cancer Center Chapel Hill NC USA
Citace poskytuje Crossref.org
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