Polygenic Risk Score Modifies Prostate Cancer Risk of Pathogenic Variants in Men of African Ancestry

被引：0

作者：

Hughley, Raymond W. ^{[1
]}

Matejcic, Marco ^{[1
]}

Song, Ziwei ^{[2
]}

Sheng, Xin ^{[1
]}

Wan, Peggy ^{[1
]}

Xia, Lucy ^{[1
]}

Hart, Steven N. ^{[3
]}

Hu, Chunling ^{[4
]}

Yadav, Siddhartha ^{[5
]}

Lubmawa, Alexander ^{[6
]}

Kiddu, Vicky ^{[6
]}

Asiimwe, Frank ^{[7
]}

Amanya, Colline ^{[8
]}

Mutema, George ^{[9
]}

Job, Kuteesa ^{[10
]}

Ssebakumba, Mbaaga K. ^{[10
]}

Ingles, Sue A. ^{[1
]}

Hamilton, Ann S. ^{[2
]}

Couch, Fergus J. ^{[3
,4
]}

Watya, Stephen ^{[6
,8
]}

Conti, David V. ^{[1
]}

Darst, Burcu F. ^{[1
,11
]}

Haiman, Christopher A. ^{[1
,12
]}

机构：

[1] Univ Southern Calif, Ctr Genet Epidemiol, Keck Sch Med, Dept Populat & Publ Hlth Sci, Los Angeles, CA USA

[2] Univ Southern Calif, Keck Sch Med, Dept Populat & Publ Hlth Sci, Los Angeles, CA USA

[3] Mayo Clin, Dept Quantitat Hlth Sci, Rochester, MN USA

[4] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA

[5] Mayo Clin, Dept Oncol, Rochester, MN USA

[6] Uro Care, Kampala, Uganda

[7] Mulago Hosp, Kampala, Uganda

[8] Makerere Univ, Coll Hlth Sci, Kampala, Uganda

[9] SurgPath, Kampala, Uganda

[10] Kagando Hosp, Kasese, Uganda

[11] Fred Hutchinson Canc Ctr, Publ Hlth Sci, Seattle, WA USA

[12] Univ Southern Calif, 1450 Biggy St, Los Angeles, CA 90033 USA

来源：

CANCER RESEARCH COMMUNICATIONS | 2023年 / 3卷 / 12期

关键词：

AMERICAN MEN; MUTATIONS;

D O I：

10.1158/2767-9764.CRC-23-0022

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Prostate cancer risk is influenced by rare and common germline variants. We examined the aggregate association of rare germline pathogenic/likely pathogenic/deleterious (P/LP/D) variants in ATM, BRCA2, PALB2, and NBN with a polygenic risk score (PRS) on prostate cancer risk among 1,796 prostate cancer cases (222 metastatic) and 1,424 controls of African ancestry. Relative to P/LP/D non-carriers at average genetic risk (33%-66% of PRS), men with low (0%-33%) and high (66%-100%) PRS had Odds Ratios (ORs) for overall prostate cancer of 2.08 [95% confidence interval (CI) = 0.58-7.49] and 18.06 (95% CI = 4.24-76.84) among P/LP/D carriers and 0.57 (95% CI = 0.46-0.71) and 3.02 (95% CI = 2.53-3.60) among non-carriers, respectively. The OR for metastatic prostate cancer was 2.73 (95% CI = 0.24-30.54) and 28.99 (95% CI = 4.39-191.43) among P/LP/D carriers and 0.54 (95% CI = 0.31-0.95) and 3.22 (95% CI = 2.20-4.73) among non-carriers, for men with low and high PRS, respectively. Lifetime absolute risks of overall prostate cancer increased with PRS (low to high) from 9.8% to 51.5% in P/LP/D carriers and 5.5% to 23.9% in non-carriers. Lifetime absolute risks of metastatic prostate cancer increased with PRS from 1.9% to 18.1% in P/LP/D carriers and 0.3% to 2.2% in non-carriers These findings suggest that assessment of prostate cancer risk for rare variant carriers should include PRS status.Significance: These findings highlight the importance of considering rare and common variants to comprehensively assess prostate cancer risk in men of African ancestry.

引用

页码：2544 / 2550

页数：7

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