Large-scale cross-cancer fine-mapping of the 5p15.33 region reveals multiple independent signals.
View/ Open
Date
2021-07-08Author
Chen, H
Majumdar, A
Wang, L
Kar, S
Brown, KM
Feng, H
Turman, C
Dennis, J
Easton, D
Michailidou, K
Simard, J
Breast Cancer Association Consortium (BCAC),
Bishop, T
Cheng, IC
Huyghe, JR
Schmit, SL
Colorectal Transdisciplinary Study (CORECT),
Colon Cancer Family Registry Study (CCFR),
Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO),
O'Mara, TA
Spurdle, AB
Endometrial Cancer Association Consortium (ECAC),
Gharahkhani, P
Schumacher, J
Jankowski, J
Gockel, I
Esophageal Cancer GWAS Consortium,
Bondy, ML
Houlston, RS
Jenkins, RB
Melin, B
Glioma International Case Control Consortium (GICC),
Lesseur, C
Ness, AR
Diergaarde, B
Olshan, AF
Head-Neck Cancer GWAS Consortium,
Amos, CI
Christiani, DC
Landi, MT
McKay, JD
International Lung Cancer Consortium (ILCCO),
Brossard, M
Iles, MM
Law, MH
MacGregor, S
Melanoma GWAS Consortium,
Beesley, J
Jones, MR
Tyrer, J
Winham, SJ
Ovarian Cancer Association Consortium (OCAC),
Klein, AP
Petersen, G
Li, D
Wolpin, BM
Pancreatic Cancer Case-Control Consortium (PANC4),
Pancreatic Cancer Cohort Consortium (PanScan),
Eeles, RA
Haiman, CA
Kote-Jarai, Z
Schumacher, FR
PRACTICAL consortium,
CRUK,
BPC3,
CAPS,
PEGASUS,
Brennan, P
Chanock, SJ
Gaborieau, V
Purdue, MP
Renal Cancer GWAS Consortium,
Pharoah, P
Hung, RJ
Amundadottir, LT
Kraft, P
Pasaniuc, B
Lindström, S
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Breast Cancer Association Consortium (BCAC)
Colorectal Transdisciplinary Study (CORECT)
Colon Cancer Family Registry Study (CCFR)
Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO)
Endometrial Cancer Association Consortium (ECAC)
Esophageal Cancer GWAS Consortium
Glioma International Case Control Consortium (GICC)
Head-Neck Cancer GWAS Consortium
International Lung Cancer Consortium (ILCCO)
Melanoma GWAS Consortium
Ovarian Cancer Association Consortium (OCAC)
Pancreatic Cancer Case-Control Consortium (PANC4)
Pancreatic Cancer Cohort Consortium (PanScan)
PRACTICAL consortium
CRUK
BPC3
CAPS
PEGASUS
Renal Cancer GWAS Consortium
Research team
Cancer Genomics
Oncogenetics
Language
eng
Date accepted
2021-06-04
Citation
HGG advances, 2021, 2 (3), pp. 100041 - ?
Publisher
ELSEVIER
Except where otherwise noted, this item's license is described
as
http://creativecommons.org/licenses/by/4.0/
Related items
Showing items related by title, author, creator and subject.
-
Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.
Fehringer, G; Kraft, P; Pharoah, PD; Eeles, RA; Chatterjee, N; et al. (AMER ASSOC CANCER RESEARCH, 2016-09-01)Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, ... -
Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.
Schumacher, FR; Al Olama, AA; Berndt, SI; Benlloch, S; Ahmed, M; et al. (NATURE PORTFOLIO, 2018-07-01)Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 ... -
Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers.
Zhang, YD; Hurson, AN; Zhang, H; Choudhury, PP; Easton, DF; et al. (NATURE PORTFOLIO, 2020-07-03)Genome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse summary-level data from GWAS of ...