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

Anqi Wang; Yili Xu; Yao Yu; Kevin T. Nead; Tae Beom Kim; Keren Xu; Tokhir Dadaev; Ed Saunders; Xin Sheng; Peggy Wan; Loreall Pooler; Lucy Y. Xia; Stephen Chanock; Sonja I. Berndt; Susan M. Gapstur; Victoria Stevens; Demetrius Albanes; Stephanie J. Weinstein; Vincent Gnanapragasam; Graham G. Giles; Tu Nguyen-Dumont; Roger L. Milne; Mark M. Pomerantz; Julie A. Schmidt; Konrad H. Stopsack; Lorelei A. Mucci; William J. Catalona; Kurt N. Hetrick; Kimberly F. Doheny; Robert J. MacInnis; Melissa C. Southey; Rosalind A. Eeles; Fredrik Wiklund; Zsofia Kote-Jarai; Adam J. Smith; David V. Conti; Chad Huff; Christopher A. Haiman; Burcu F. Darst

doi:10.1093/hmg/ddac214

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

Anqi Wang, Yili Xu, Yao Yu, Kevin T. Nead, Tae Beom Kim, Keren Xu, Tokhir Dadaev, Ed Saunders, Xin Sheng, Peggy Wan, Loreall Pooler, Lucy Y. Xia, Stephen Chanock, Sonja I. Berndt, Susan M. Gapstur, Victoria Stevens, Demetrius Albanes, Stephanie J. Weinstein, Vincent Gnanapragasam, Graham G. GilesTu Nguyen-Dumont, Roger L. Milne, Mark M. Pomerantz, Julie A. Schmidt, Konrad H. Stopsack, Lorelei A. Mucci, William J. Catalona, Kurt N. Hetrick, Kimberly F. Doheny, Robert J. MacInnis, Melissa C. Southey, Rosalind A. Eeles, Fredrik Wiklund, Zsofia Kote-Jarai, Adam J. Smith, David V. Conti, Chad Huff, Christopher A. Haiman, Burcu F. Darst

School of Medicine

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	489-495
Number of pages	7
Journal	Human molecular genetics
Volume	32
Issue number	3
DOIs	https://doi.org/10.1093/hmg/ddac214
State	Published - Feb 1 2023

ASJC Scopus subject areas

Genetics(clinical)
Genetics
Molecular Biology

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Wang, A., Xu, Y., Yu, Y., Nead, K. T., Kim, T. B., Xu, K., Dadaev, T., Saunders, E., Sheng, X., Wan, P., Pooler, L., Xia, L. Y., Chanock, S., Berndt, S. I., Gapstur, S. M., Stevens, V., Albanes, D., Weinstein, S. J., Gnanapragasam, V., ... Darst, B. F. (2023). Clonal hematopoiesis and risk of prostate cancer in large samples of European ancestry men. Human molecular genetics, 32(3), 489-495. https://doi.org/10.1093/hmg/ddac214

Wang, A, Xu, Y, Yu, Y, Nead, KT, Kim, TB, 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, 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, Smith, AJ, Conti, DV, Huff, C, Haiman, CA & Darst, BF 2023, 'Clonal hematopoiesis and risk of prostate cancer in large samples of European ancestry men', Human molecular genetics, vol. 32, no. 3, pp. 489-495. https://doi.org/10.1093/hmg/ddac214

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title = "Clonal hematopoiesis and risk of prostate cancer in large samples of European ancestry men",

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.",

author = "Anqi Wang and Yili Xu and Yao Yu and Nead, {Kevin T.} and Kim, {Tae Beom} and Keren Xu and Tokhir Dadaev and Ed Saunders and Xin Sheng and Peggy Wan and Loreall Pooler and Xia, {Lucy Y.} and Stephen Chanock and Berndt, {Sonja I.} and Gapstur, {Susan M.} and Victoria Stevens and Demetrius Albanes and Weinstein, {Stephanie J.} and Vincent Gnanapragasam and Giles, {Graham G.} and Tu Nguyen-Dumont and Milne, {Roger L.} and Pomerantz, {Mark M.} and Schmidt, {Julie A.} and Stopsack, {Konrad H.} and Mucci, {Lorelei A.} and Catalona, {William J.} and Hetrick, {Kurt N.} and Doheny, {Kimberly F.} and MacInnis, {Robert J.} and Southey, {Melissa C.} and Eeles, {Rosalind A.} and Fredrik Wiklund and Zsofia Kote-Jarai and Smith, {Adam J.} and Conti, {David V.} and Chad Huff and Haiman, {Christopher A.} and Darst, {Burcu F.}",

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doi = "10.1093/hmg/ddac214",

language = "English (US)",

volume = "32",

pages = "489--495",

journal = "Human molecular genetics",

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T1 - Clonal hematopoiesis and risk of prostate cancer in large samples of European ancestry men

AU - Wang, Anqi

AU - Xu, Yili

AU - Yu, Yao

AU - Nead, Kevin T.

AU - Kim, Tae Beom

AU - Xu, Keren

AU - Dadaev, Tokhir

AU - Saunders, Ed

AU - Sheng, Xin

AU - Wan, Peggy

AU - Pooler, Loreall

AU - Xia, Lucy Y.

AU - Chanock, Stephen

AU - Berndt, Sonja I.

AU - Gapstur, Susan M.

AU - Stevens, Victoria

AU - Albanes, Demetrius

AU - Weinstein, Stephanie J.

AU - Gnanapragasam, Vincent

AU - Giles, Graham G.

AU - Nguyen-Dumont, Tu

AU - Milne, Roger L.

AU - Pomerantz, Mark M.

AU - Schmidt, Julie A.

AU - Stopsack, Konrad H.

AU - Mucci, Lorelei A.

AU - Catalona, William J.

AU - Hetrick, Kurt N.

AU - Doheny, Kimberly F.

AU - MacInnis, Robert J.

AU - Southey, Melissa C.

AU - Eeles, Rosalind A.

AU - Wiklund, Fredrik

AU - Kote-Jarai, Zsofia

AU - Smith, Adam J.

AU - Conti, David V.

AU - Huff, Chad

AU - Haiman, Christopher A.

AU - Darst, Burcu F.

PY - 2023/2/1

Y1 - 2023/2/1

N2 - 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.

AB - 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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ER -

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

Abstract

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