Pierre-Antoine Dugué1,2, James G Dowty2, Jihoon E Joo3, Ee M Wong3,4, Enes Makalic2, Daniel F Schmidt2,5, Dallas R English1,2, John L Hopper2, John Pedersen6, Gianluca Severi1,2,7, Robert J MacInnis1,2, Roger L Milne1,2,4, Graham G Giles1,2, Melissa C Southey3,4. 1. Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Victoria, Australia. 2. Centre for Epidmiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia. 3. Genetic Epidemiology Laboratory, Department of Clinical Pathology, The University of Melbourne, Victoria, Australia. 4. Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia. 5. Faculty of Information Technology, Monash University, Victoria, Australia. 6. TissuPath, Mount Waverley, Australia. 7. Centre de Recherche en Épidémiologie et Santé des Populations (CESP, Inserm U1018), Université Paris-Saclay, UPS, UVSQ, Gustave Roussy, Villejuif, France.
Abstract
BACKGROUND: DNA methylation can mimic the effects of germline mutations in cancer predisposition genes. Recently, we identified twenty-four heritable methylation marks associated with breast cancer risk. As breast and prostate cancer share genetic risk factors, including rare, high-risk mutations (eg, in BRCA2), we hypothesized that some of these heritable methylation marks might also be associated with the risk of prostate cancer. METHODS: We studied 869 incident prostate cancers (430 aggressive and 439 non-aggressive) and 869 matched controls nested within a prospective cohort study. DNA methylation was measured in pre-diagnostic blood samples using the Illumina Infinium HM450K BeadChip. Conditional logistic regression models, adjusted for prostate cancer risk factors and blood cell composition, were used to estimate odds ratios and 95% confidence intervals for the association between the 24 methylation marks and the risk of prostate cancer. RESULTS: Five methylation marks within the VTRNA2-1 promoter region (cg06536614, cg00124993, cg26328633, cg25340688, and cg26896946), and one in the body of CLGN (cg22901919) were associated with the risk of prostate cancer. In stratified analyses, the five VTRNA2-1 marks were associated with the risk of aggressive prostate cancer. CONCLUSIONS: This work highlights a potentially important new area of investigation for prostate cancer susceptibility and adds to our knowledge about shared risk factors for breast and prostate cancer.
BACKGROUND: DNA methylation can mimic the effects of germline mutations in cancer predisposition genes. Recently, we identified twenty-four heritable methylation marks associated with breast cancer risk. As breast and prostate cancer share genetic risk factors, including rare, high-risk mutations (eg, in BRCA2), we hypothesized that some of these heritable methylation marks might also be associated with the risk of prostate cancer. METHODS: We studied 869 incident prostate cancers (430 aggressive and 439 non-aggressive) and 869 matched controls nested within a prospective cohort study. DNA methylation was measured in pre-diagnostic blood samples using the Illumina Infinium HM450K BeadChip. Conditional logistic regression models, adjusted for prostate cancer risk factors and blood cell composition, were used to estimate odds ratios and 95% confidence intervals for the association between the 24 methylation marks and the risk of prostate cancer. RESULTS: Five methylation marks within the VTRNA2-1 promoter region (cg06536614, cg00124993, cg26328633, cg25340688, and cg26896946), and one in the body of CLGN (cg22901919) were associated with the risk of prostate cancer. In stratified analyses, the five VTRNA2-1 marks were associated with the risk of aggressive prostate cancer. CONCLUSIONS: This work highlights a potentially important new area of investigation for prostate cancer susceptibility and adds to our knowledge about shared risk factors for breast and prostate cancer.
Authors: Saara Marttila; Leena E Viiri; Pashupati P Mishra; Brigitte Kühnel; Pamela R Matias-Garcia; Leo-Pekka Lyytikäinen; Tiina Ceder; Nina Mononen; Wolfgang Rathmann; Juliane Winkelmann; Annette Peters; Mika Kähönen; Nina Hutri-Kähönen; Markus Juonala; Katriina Aalto-Setälä; Olli Raitakari; Terho Lehtimäki; Melanie Waldenberger; Emma Raitoharju Journal: Clin Epigenetics Date: 2021-07-22 Impact factor: 6.551
Authors: Pierre-Antoine Dugué; Chenglong Yu; Timothy McKay; Ee Ming Wong; Jihoon Eric Joo; Helen Tsimiklis; Fleur Hammet; Maryam Mahmoodi; Derrick Theys; John L Hopper; Graham G Giles; Roger L Milne; Jason A Steen; James G Dowty; Tu Nguyen-Dumont; Melissa C Southey Journal: Int J Mol Sci Date: 2021-03-03 Impact factor: 5.923