An integrative multi-omics analysis to identify candidate DNA methylation biomarkers related to prostate cancer risk
Authors: Wu Lang , Yang Yaohua , Guo Xingyi , Shu Xiao-Ou , Cai Qiuyin , Shu Xiang , Li Bingshan , Tao Ran , Wu Chong , Nikas Jason B. , Sun Yanfa , Zhu Jingjing , Roobol Monique J. , Giles Graham G. , Brenner Hermann , John Esther M. , Clements Judith , Grindedal Eli Marie , Park Jong Y. , Stanford Janet L. , Kote-Jarai Zsofia , Haiman Christopher A. , Eeles Rosalind A. , Zheng Wei , Long Jirong ,   The PRACTICAL consortium, Eeles Rosalind A. , Henderson Brian E. , Haiman Christopher A. , Kote-Jarai Zsofia , Schumacher Fredrick R. , Easton Douglas , Benlloch Sara , Olama Ali Amin Al , Muir Kenneth , Berndt Sonja I. , Conti David V. , Wiklund Fredrik , Chanock Stephen , Gapstur Susan M. , Stevens Victoria L. , Tangen Catherine M. , Batra Jyotsna , Clements Judith , Gronberg Henrik , Pashayan Nora , Schleutker Johanna , Albanes Demetrius , Weinstein Stephanie , Wolk Alicja , West Catharine , Mucci Lorelei , Cancel-Tassin Géraldine , Koutros Stella , Sorensen Karina Dalsgaard , Grindedal Eli Marie , Neal David E. , Hamdy Freddie C. , Donovan Jenny L. , Travis Ruth C. , Hamilton Robert J. , Ingles Sue Ann , Rosenstein Barry S. , Lu Yong-Jie , Giles Graham G. , Kibel Adam S. , Vega Ana , Kogevinas Manolis , Penney Kathryn L. , Park Jong Y. , Stanford Janet L. , Cybulski Cezary , Nordestgaard Børge G. , Brenner Hermann , Maier Christiane , Kim Jeri , John Esther M. , Teixeira Manuel R. , Neuhausen Susan L. , De Ruyck Kim , Razack Azad , Newcomb Lisa F. , Gamulin Marija , Kaneva Radka , Usmani Nawaid , Claessens Frank , Townsend Paul A. , Dominguez Manuela Gago , Roobol Monique J. , Menegaux Florence , Khaw Kay-Tee , Cannon-Albright Lisa , Pandha Hardev , Thibodeau Stephen N. , Hunter David J. , Blot William J. , Riboli Elio ,   CRUK Consortium, Eeles Rosalind A. , Kote-Jarai Zsofia , West Catharine , Neal David E. , Hamdy Freddie C. , Donovan Jenny L. , Travis Ruth C. , Riboli Elio ,   BPC3 Consortium, Henderson Brian E. , Haiman Christopher A. , Schumacher Fredrick R. , Berndt Sonja I. , Chanock Stephen , Gapstur Susan M. , Stevens Victoria L. , Albanes Demetrius , Weinstein Stephanie , Mucci Lorelei , Koutros Stella , Travis Ruth C. , Penney Kathryn L. , Hunter David J. , Riboli Elio ,   CAPS Consortium, Wiklund Fredrik , Gronberg Henrik ,   PEGASUS Consortium, Berndt Sonja I. , Chanock Stephen , Albanes Demetrius , Weinstein Stephanie , Koutros Stella 
Published: August 2020

It remains elusive whether some of the associations identified in genome-wide association studies of prostate cancer (PrCa) may be due to regulatory effects of genetic variants on CpG sites, which may further influence expression of PrCa target genes. To search for CpG sites associated with PrCa risk, here we establish genetic models to predict methylation (N = 1,595) and conduct association analyses with PrCa risk (79,194 cases and 61,112 controls). We identify 759 CpG sites showing an association, including 15 located at novel loci. Among those 759 CpG sites, methylation of 42 is associated with expression of 28 adjacent genes. Among 22 genes, 18 show an association with PrCa risk. Overall, 25 CpG sites show consistent association directions for the methylation-gene expression-PrCa pathway. We identify DNA methylation biomarkers associated with PrCa, and our findings suggest that specific CpG sites may influence PrCa via regulating expression of candidate PrCa target genes.