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

Anqi Wang¹, Yili Xu¹, Yao Yu², Kevin T Nead², TaeBeom Kim², Keren Xu¹, Tokhir Dadaev³, Ed Saunders³, Xin Sheng¹, Peggy Wan¹, Loreall Pooler¹, Lucy Y Xia¹, Stephen Chanock⁴, Sonja I Berndt⁴, Susan M Gapstur⁵, Victoria Stevens⁵, Demetrius Albanes⁴, Stephanie J Weinstein⁴, Vincent Gnanapragasam⁶, Graham G Giles^{7

8

9}, Tu Nguyen-Dumont^{8

10}, Roger L Milne^{7

8

9}, Mark M Pomerantz¹¹, Julie A Schmidt^{12

13}, Konrad H Stopsack¹⁴, Lorelei A Mucci¹⁴, William J Catalona¹⁵, Kurt N Hetrick¹⁶, Kimberly F Doheny¹⁶, Robert J MacInnis^{7

9}, Melissa C Southey^{7

8

10}, Rosalind A Eeles^{4

17}, Fredrik Wiklund¹⁸, Zsofia Kote-Jarai³, Adam J de Smith¹, David V Conti¹, Chad Huff², Christopher A Haiman¹, Burcu F Darst^{1

19}

Affiliations

¹ Department of Population and Public Health Sciences, Center for Genetic Epidemiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
² Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77230, USA.
³ The Institute of Cancer Research, London, SM2 5NG, UK.
⁴ National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
⁵ American Cancer Society, Atlanta, GA 30303, USA.
⁶ Division of Urology, Department of Surgery, University of Cambridge, Cambridge, CB2 0QQ, UK.
⁷ Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria 3004, Australia.
⁸ Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Victoria 3168, Australia.
⁹ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Victoria 3010, Australia.
¹⁰ Department of Clinical Pathology, The University of Melbourne, Victoria 3010, Australia.
¹¹ Dana-Farber Cancer Institute, Boston, MA 02215, USA.
¹² Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK.
¹³ Department of Clinical Epidemiology, Department of Clinical Medicine, Aarhus University Hospital and Aarhus University, Aarhus N, DK-8200, Denmark.
¹⁴ Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
¹⁵ Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
¹⁶ Department of Genetic Medicine, Center for Inherited Disease Research, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
¹⁷ The Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK.
¹⁸ Karolinska Institute, Solna 171 77, Sweden.
¹⁹ Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.

PMID: 36018819
PMCID: PMC9851740
DOI: 10.1093/hmg/ddac214

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

Anqi Wang et al. Hum Mol Genet. 2023.

. 2023 Jan 13;32(3):489-495.

doi: 10.1093/hmg/ddac214.

Authors

Affiliations

¹ Department of Population and Public Health Sciences, Center for Genetic Epidemiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
² Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77230, USA.
³ The Institute of Cancer Research, London, SM2 5NG, UK.
⁴ National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
⁵ American Cancer Society, Atlanta, GA 30303, USA.
⁶ Division of Urology, Department of Surgery, University of Cambridge, Cambridge, CB2 0QQ, UK.
⁷ Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria 3004, Australia.
⁸ Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Victoria 3168, Australia.
⁹ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Victoria 3010, Australia.
¹⁰ Department of Clinical Pathology, The University of Melbourne, Victoria 3010, Australia.
¹¹ Dana-Farber Cancer Institute, Boston, MA 02215, USA.
¹² Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK.
¹³ Department of Clinical Epidemiology, Department of Clinical Medicine, Aarhus University Hospital and Aarhus University, Aarhus N, DK-8200, Denmark.
¹⁴ Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
¹⁵ Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
¹⁶ Department of Genetic Medicine, Center for Inherited Disease Research, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
¹⁷ The Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK.
¹⁸ Karolinska Institute, Solna 171 77, Sweden.
¹⁹ Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.

PMID: 36018819
PMCID: PMC9851740
DOI: 10.1093/hmg/ddac214

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.

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Figures

**Figure 1**
Manhattan plots of associations between CHIP genes and age at blood draw in the UK Biobank.

See this image and copyright information in PMC

References

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

Affiliations

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

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical