Rare germline genetic variants and risk of aggressive prostate cancer

T. Nguyen-Dumont; Robert J. MacInnis; Jason A. Steen; Derrick Theys; Helen Tsimiklis; Fleur Hammet; Maryam Mahmoodi; Bernard J. Pope; Daniel J. Park; Khalid Mahmood; Gianluca Severi; Damien Bolton; Roger L. Milne; Graham G. Giles; Melissa C. Southey

doi:10.1002/ijc.33024

Rare germline genetic variants and risk of aggressive prostate cancer

T. Nguyen-Dumont, Robert J. MacInnis, Jason A. Steen, Derrick Theys, Helen Tsimiklis, Fleur Hammet, Maryam Mahmoodi, Bernard J. Pope, Daniel J. Park, Khalid Mahmood, Gianluca Severi, Damien Bolton, Roger L. Milne, Graham G. Giles, Melissa C. Southey

Medicine Monash Health

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

14 Citations (Scopus)

Abstract

Few genetic risk factors have been demonstrated to be specifically associated with aggressive prostate cancer (PrCa). Here, we report a case-case study of PrCa comparing the prevalence of germline pathogenic/likely pathogenic (P/LP) genetic variants in 787 men with aggressive disease and 769 with nonaggressive disease. Overall, we observed P/LP variants in 11.4% of men with aggressive PrCa and 9.8% of men with nonaggressive PrCa (two-tailed Fisher's exact tests, P =.28). The proportion of BRCA2 and ATM P/LP variant carriers in men with aggressive PrCa exceeded that observed in men with nonaggressive PrCa; 18/787 carriers (2.3%) and 4/769 carriers (0.5%), P =.004, and 14/787 carriers (0.02%) and 5/769 carriers (0.01%), P =.06, respectively. Our findings contribute to the extensive international effort to interpret the genetic variation identified in genes included on gene-panel tests, for which there is currently an insufficient evidence-base for clinical translation in the context of PrCa risk.

Original language	English
Pages (from-to)	2142-2149
Number of pages	8
Journal	International Journal of Cancer
Volume	147
Issue number	8
DOIs	https://doi.org/10.1002/ijc.33024
Publication status	Published - 15 Oct 2020

Keywords

aggressive prostate cancer
gene panel testing
germline genetic variants

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/ijc.33024

Cite this

Nguyen-Dumont, T., MacInnis, R. J., Steen, J. A., Theys, D., Tsimiklis, H., Hammet, F., Mahmoodi, M., Pope, B. J., Park, D. J., Mahmood, K., Severi, G., Bolton, D., Milne, R. L., Giles, G. G., & Southey, M. C. (2020). Rare germline genetic variants and risk of aggressive prostate cancer. International Journal of Cancer, 147(8), 2142-2149. https://doi.org/10.1002/ijc.33024

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abstract = "Few genetic risk factors have been demonstrated to be specifically associated with aggressive prostate cancer (PrCa). Here, we report a case-case study of PrCa comparing the prevalence of germline pathogenic/likely pathogenic (P/LP) genetic variants in 787 men with aggressive disease and 769 with nonaggressive disease. Overall, we observed P/LP variants in 11.4% of men with aggressive PrCa and 9.8% of men with nonaggressive PrCa (two-tailed Fisher's exact tests, P =.28). The proportion of BRCA2 and ATM P/LP variant carriers in men with aggressive PrCa exceeded that observed in men with nonaggressive PrCa; 18/787 carriers (2.3%) and 4/769 carriers (0.5%), P =.004, and 14/787 carriers (0.02%) and 5/769 carriers (0.01%), P =.06, respectively. Our findings contribute to the extensive international effort to interpret the genetic variation identified in genes included on gene-panel tests, for which there is currently an insufficient evidence-base for clinical translation in the context of PrCa risk.",

keywords = "aggressive prostate cancer, gene panel testing, germline genetic variants",

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AU - Hammet, Fleur

AU - Mahmoodi, Maryam

AU - Pope, Bernard J.

AU - Park, Daniel J.

AU - Mahmood, Khalid

AU - Severi, Gianluca

AU - Bolton, Damien

AU - Milne, Roger L.

AU - Giles, Graham G.

AU - Southey, Melissa C.

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N2 - Few genetic risk factors have been demonstrated to be specifically associated with aggressive prostate cancer (PrCa). Here, we report a case-case study of PrCa comparing the prevalence of germline pathogenic/likely pathogenic (P/LP) genetic variants in 787 men with aggressive disease and 769 with nonaggressive disease. Overall, we observed P/LP variants in 11.4% of men with aggressive PrCa and 9.8% of men with nonaggressive PrCa (two-tailed Fisher's exact tests, P =.28). The proportion of BRCA2 and ATM P/LP variant carriers in men with aggressive PrCa exceeded that observed in men with nonaggressive PrCa; 18/787 carriers (2.3%) and 4/769 carriers (0.5%), P =.004, and 14/787 carriers (0.02%) and 5/769 carriers (0.01%), P =.06, respectively. Our findings contribute to the extensive international effort to interpret the genetic variation identified in genes included on gene-panel tests, for which there is currently an insufficient evidence-base for clinical translation in the context of PrCa risk.

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Rare germline genetic variants and risk of aggressive prostate cancer

Abstract

Keywords

UN SDGs

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Precision Medicine for Prostate and Breast Cancer

Precision Public Health for major cancers - novel approaches to building the genetic, epigenetic and lifestyle knowledge base for assessing risk and prognosis

Cite this

Rare germline genetic variants and risk of aggressive prostate cancer

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Projects

Precision Medicine for Prostate and Breast Cancer

Precision Public Health for major cancers - novel approaches to building the genetic, epigenetic and lifestyle knowledge base for assessing risk and prognosis

Cite this