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Autor
Amos, Christopher I 1 Amundadottir, Laufey T 1 Beesley, Jonathan 1 Bishop, Timothy 1 Bondy, Melissa L 1 Brennan, Paul 1 Brossard, Myriam 1 Brown, Kevin M 1 Chanock, Stephen J 1 Chen, Hongjie 1 Cheng, Iona C 1 Christiani, David C 1 Dennis, Joe 1 Diergaarde, Brenda 1 Easton, Douglas 1 Eeles, Rosalind A 1 Feng, Helian 1 Gaborieau, Valerie 1 Gharahkhani, Puya 1 Gockel, Ines 1
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Organizace
BPC3 1 Breast Cancer Association Consortium (BCAC) 1 CAPS 1 CRUK 1 Colon Cancer Family Registry Study (CCFR) 1 Colorectal Transdisciplinary Study (CORECT) 1 Endometrial Cancer Association Consortium (E... 1 Esophageal Cancer GWAS Consortium 1 Genetics and Epidemiology of Colorectal Canc... 1 Glioma International Case Control Consortium... 1 Head-Neck Cancer GWAS Consortium 1 International Lung Cancer Consortium (ILCCO) 1 Melanoma GWAS Consortium 1 Ovarian Cancer Association Consortium (OCAC) 1 PEGASUS 1 PRACTICAL consortium 1 Pancreatic Cancer Case-Control Consortium (P... 1 Pancreatic Cancer Cohort Consortium (PanScan) 1 Renal Cancer GWAS Consortium 1
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Pracoviště
Biostatistics Unit The Cyprus Institute of N... 1 Bristol Dental School University of Bristol ... 1 Cancer Genetics Unit Royal Marsden NHS Found... 1 Center for Bioinformatics and Functional Gen... 1 Center for Human Genetics University Hospita... 1 Centre for Cancer Genetic Epidemiology Depar... 1 College of Medicine and Health Sciences Unit... 1 Comprehensive Clinical Trials Unit Universit... 1 Cyprus School of Molecular Medicine Nicosia ... 1 Department of Biostatistics Harvard T H Chan... 1 Department of Computational Medicine David G... 1 Department of Environmental Health Harvard T... 1 Department of Environmental Medicine and Pub... 1 Department of Environmental and Occupational... 1 Department of Epidemiology Gillings School o... 1 Department of Epidemiology Harvard T H Chan ... 1 Department of Epidemiology University of Was... 1 Department of Epidemiology and Biostatistics... 1 Department of Epidemiology and Biostatistics... 1 Department of Epidemiology and Population He... 1
- Formát
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NLK
Directory of Open Access Journals
od 2020
PubMed Central
od 2020
ROAD: Directory of Open Access Scholarly Resources
od 2020
PubMed
34355204
DOI
10.1016/j.xhgg.2021.100041
Knihovny.cz E-zdroje
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.
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