Citations 3
Genome-wide analyses characterize shared heritability among cancers and identify novel cancer susceptibility regions
Lindström, Sara , Wang, Lu , Feng, Helian , Huo, Sijia , Harrison, Tabitha A. , Turman, Constance , Chen, Hongjie , Bammler, Theo K. , Gallinger, Steve, Gruber, Stephen B. , Moreno, Vı́ctor , Offit, Kenneth , O’Mara, Tracy A. , Tomlinson, Ian, Gharahkhani, Puya , MacGregor, Stuart , Schumacher, Johannes , Bondy, Melissa L. , Houlston, Richard S. , Jenkins, Robert B. , Melin, Beatrice , Wrensch, Margaret , Brennan, Paul , Johansson, Mattias , McKay, James , Aldrich, Melinda C. , Landi, Maria Teresa , Bishop, D. Timothy , Iles, Mark M. , Law, Matthew H. , Wolpin, Brian M. , Petersen, Gloria M. , Purdue, Mark P. , Scélo, Ghislaine , Kar, Siddhartha , Hung, Rayjean J, Kraft, Peter , Lissowska, Jolanta , Simard, Jacques , Dörk, Thilo , John, Esther M. , Carracedo, Ãngel , Huang, Wen‐Yi , Vodička, Pavel , Taylor, Jack A. , Lessel, Davor , Kurian, Allison W. , Hung, Rayjean J. , Kundaje, Anshul , Zhong, Jun , Turman, Constance , Chen, Hongjie , Gruber, Stephen B , Marchand, Loïc Le , Moreno, Victor , Offit, Kenneth , Gharahkhani, Puya , MacGregor, Stuart , Schumacher, Johannes , Houlston, Richard S , Brennan, Paul , Johansson, Mattias , Iles, Mark M , Law, Matthew H , Amundadottir, Laufey , Klein, Alison P , Petersen, Gloria, Chanock, Stephen Jacob , Kar, Siddhartha , Kraft, Peter , Dörk, Thilo , Lissowska, Jolanta , John, Esther M , Hung, Rayjean J , Harrison, Tabitha A , O'Mara, Tracy A , Lessel, Davor , Bishop, D Timothy , Huang, Wen-Yi , Taylor, Jack A , Simard, Jacques , Kurian, Allison W , Kundaje, Anshul , Vodicka, Pavel , Zhong, Jun , Majumdar, Arunabha , MacDonald, James W. , Mancuso, Nicholas , Gunter, Marc J. , Marchand, Loı̈c Le , Vivo, Immaculata De , Spurdle, Amanda B. , Fitzgerald, Rebecca C. , Gockel, Ines , Jankowski, Janusz , Barnholtz‐Sloan, Jill S. , Christiani, David C. , Amos, Christopher I. , Tardón, Adonina , Démenais, Florence , Goldstein, Alisa M. , Kanetsky, Peter A. , Ámundadóttir, Laufey T. , Stolzenberg‐Solomon, Rachael Z. , Klein, Alison P. , Risch, Harvey A. , Pharoah, Paul D.P. , Paşaniuc, Bogdan
JNCI: Journal of the National Cancer Institute | March 17, 2023 | Volume: 115 | Issue: 6 | Pages: 712-732
Abstract Background The shared inherited genetic contribution to risk of different cancers is not fully known. In this study, we leverage results from 12 cancer genome-wide association studies (GWAS) to quantify pairwise genome-wide genetic correlations across cancers and identify novel cancer susceptibility loci. Methods We collected GWAS summary statistics for 12 solid cancers based on 376 759 participants with cancer and 532 864 participants without cancer of European ancestry. The included cancer types were breast, colorectal, endometrial, esophageal, glioma, head and neck, lung, melanoma, ovarian, pancreatic, prostate, and renal cancers. We conducted cross-cancer GWAS and transcriptome-wide association studies to discover novel cancer susceptibility loci. Finally, we assessed the extent of variant-specific pleiotropy among cancers at known and newly identified cancer susceptibility loci. Results We observed widespread but modest genome-wide genetic correlations across cancers. In cross-cancer GWAS and transcriptome-wide association studies, we identified 15 novel cancer susceptibility loci. Additionally, we identified multiple variants at 77 distinct loci with strong evidence of being associated with at least 2 cancer types by testing for pleiotropy at known cancer susceptibility loci. Conclusions Overall, these results suggest that some genetic risk variants are shared among cancers, though much of cancer heritability is cancer-specific and thus tissue-specific. The increase in statistical power associated with larger sample sizes in cross-disease analysis allows for the identification of novel susceptibility regions. Future studies incorporating data on multiple cancer types are likely to identify additional regions associated with the risk of multiple cancer types.
Rare germline variants in PALB2 and BRCA2 in familial and sporadic chordoma
Xia, Bing , Biswas, Kajal , Gomes, Thiago T. , Riedel‐Topper, Maximilian, Southon, Eileen, Reid, Susan, Stauffer, Stacey , Zhou, Weiyin , Yepes, Sally , Brodie, Seth A. , Vogt, Aurélie , Freedman, Neal D. , Hicks, Belynda , Parry, Dilys M. , Carvalho, Marcelo A. , Yang, Xiaohong R. , Sharan, Shyam K , Yang, Xiaohong R , Freedman, Neal D , Foo, Tzeh Keong , Kang, Zhihua , Huo, Yanying , Zhu, Bin , Koka, Hela , Jones, Kristine , Carter, Brian, Yeager, Meredith , Chanock, Stephen Jacob , Couch, Fergus J. , Monteiro, Álvaro N.A. , Goldstein, Alisa M. , Sharan, Shyam K.
Human Mutation | June 28, 2022 | Volume: 43 | Issue: 10 | Pages: 1396-1407
Variants Associated with Susceptibility to Pancreatic Cancer and Melanoma Do Not Reciprocally Affect Risk
Wu, Lang , Yang, Xiaohong R. , Rabe, Kari G. , Arslan, Alan A. , Canzian, Federico , Wolpin, Brian M. , Ámundadóttir, Laufey T. , Petersen, Gloria M. , Goldstein, Alisa M, Yang, Xiaohong Rose, Stolzenberg-Solomon, Rachael, Goldstein, Alisa M. , Yu, Herbert , Stolzenberg‐Solomon, Rachael Z. , Chaffee, Kari G. , Amundadottir, Laufey , Arslan, Alan A , Canzian, Federico
Cancer Epidemiology, Biomarkers & Prevention | March 19, 2014 | Volume: 23 | Issue: 6 | Pages: 1121-1124
Abstract Background: Melanoma cases may exist in pancreatic cancer kindreds, whereas there is increased risk of pancreatic cancer in familial melanoma. The two cancers may share genetic susceptibility variants in common. Methods: Three dbGaP (datasets in Genotypes and Phenotypes)-deposited GWAS (genome-wide association study) datasets (MD Anderson melanoma, PanScan 1, and PanScan 2 for pancreatic cancer) were used. Thirty-seven melanoma susceptibility variants in 22 genomic regions from published GWAS, plus melanoma-related genes and pathways were examined for pancreatic cancer risk in the PanScan datasets. Conversely, nine known pancreatic cancer susceptibility variants were examined for melanoma risk in the MD Anderson dataset. Results: In the PanScan data, initial associations were found with melanoma susceptibility variants in NCOA6 [rs4911442; OR, 1.32; 95% confidence interval (CI), 1.03–1.70; P = 0.03], YWHAZP5 (rs17119461; OR, 2.62; 95% CI, 1.08–6.35; P = 0.03), and YWHAZP5 (rs17119490; OR, 2.62; 95% CI, 1.08–6.34; P = 0.03), TYRP1 (P = 0.04), and IFNA13 (P = 0.04). In the melanoma dataset, two pancreatic cancer susceptibility variants were associated: NR5A2 (rs12029406; OR, 1.39; 95% CI, 1.01–1.92; P = 0.04) and CLPTM1L-TERT (rs401681; OR, 1.16; 95% CI, 1.01–1.34; P = 0.04). None of these associations remained significant after correcting for multiple comparisons. Conclusion: Reported variants of melanoma genes and pathways do not play a role in pancreatic cancer predisposition. Reciprocally, pancreatic cancer susceptibility variants are not associated with melanoma risk. Impact: Known melanoma-related genes and pathways, as well as GWAS-derived susceptibility variants of melanoma and pancreatic cancer, do not explain the shared genetic etiology of these two cancers. Cancer Epidemiol Biomarkers Prev; 23(6); 1121–4. ©2014 AACR.