Skip to Main Content

An official website of the United States government

Clonal hematopoiesis and risk of prostate cancer in large samples of European ancestry men.

About this Publication
Title
Clonal hematopoiesis and risk of prostate cancer in large samples of European ancestry men.
Pubmed ID
36018819 (View this publication on the PubMed website)
Digital Object Identifier
Publication
Hum Mol Genet. 2023 Jan 13; Volume 32 (Issue 3): Pages 489-495
Authors
Wang A, Xu Y, Yu Y, Nead KT, Kim T, Xu K, Dadaev T, Saunders E, Sheng X, Wan P, Pooler L, Xia LY, Chanock S, Berndt SI, Gapstur SM, Stevens V, Albanes D, Weinstein SJ, Gnanapragasam V, Giles GG, ...show more Nguyen-Dumont T, Milne RL, Pomerantz MM, Schmidt JA, Stopsack KH, Mucci LA, Catalona WJ, Hetrick KN, Doheny KF, MacInnis RJ, Southey MC, Eeles RA, Wiklund F, Kote-Jarai Z, de Smith AJ, Conti DV, Huff C, Haiman CA, Darst BF
Affiliations
  • Department of Population and Public Health Sciences, Center for Genetic Epidemiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
  • Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77230, USA.
  • The Institute of Cancer Research, London, SM2 5NG, UK.
  • National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • American Cancer Society, Atlanta, GA 30303, USA.
  • Division of Urology, Department of Surgery, University of Cambridge, Cambridge, CB2 0QQ, UK.
  • Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria 3004, Australia.
  • Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Victoria 3168, Australia.
  • Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK.
...show more
  • Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
  • Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
  • Department of Genetic Medicine, Center for Inherited Disease Research, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
  • Karolinska Institute, Solna 171 77, Sweden.
Abstract

Little is known regarding the potential relationship between clonal hematopoiesis (CH) of indeterminate potential (CHIP), which is the expansion of hematopoietic stem cells with somatic mutations, and risk of prostate cancer, the fifth leading cause of cancer death of men worldwide. We evaluated the association of age-related CHIP with overall and aggressive prostate cancer risk in two large whole-exome sequencing studies of 75 047 European ancestry men, including 7663 prostate cancer cases, 2770 of which had aggressive disease, and 3266 men carrying CHIP variants. We found that CHIP, defined by over 50 CHIP genes individually and in aggregate, was not significantly associated with overall (aggregate HR = 0.93, 95% CI = 0.76-1.13, P = 0.46) or aggressive (aggregate OR = 1.14, 95% CI = 0.92-1.41, P = 0.22) prostate cancer risk. CHIP was weakly associated with genetic risk of overall prostate cancer, measured using a polygenic risk score (OR = 1.05 per unit increase, 95% CI = 1.01-1.10, P = 0.01). CHIP was not significantly associated with carrying pathogenic/likely pathogenic/deleterious variants in DNA repair genes, which have previously been found to be associated with aggressive prostate cancer. While findings from this study suggest that CHIP is likely not a risk factor for prostate cancer, it will be important to investigate other types of CH in association with prostate cancer risk.

Related CDAS Studies
Related CDAS Projects