Abstract
Recent data suggests that African American men (AAM) with prostate cancer (PCa) exhibit
genetic alterations in highly penetrant germline genes, as well as low penetrant single
nucleotide polymorphisms. The importance of germline variants of uncertain significance
(VUS) remain poorly elucidated and given the elevated rates of VUS in AAM compared
to Caucasians with PCa, further studies are needed to facilitate potential reclassification
of VUS. Ongoing efforts to include AAM in genomics research is of paramount importance
in order to ensure applicability of discoveries across diverse populations and potentially
reduce PCa disparities as we embark on the era of precision medicine.
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References
- Cancer statistics, 2021.CA Cancer J Clin. 2021; 71: 7-33
- Cancer statistics for African Americans, 2019.CA Cancer J Clin. 2019; 69: 211-233
- Explaining racial differences in prostate cancer mortality.Cancer. 2012; 118: 4280-4289
- Novel biomarker signature that may predict aggressive disease in African American men with prostate cancer.J Clin Oncol. 2015; 33: 2789-2796
- African-American men and prostate cancer-specific mortality: a competing risk analysis of a large institutional cohort, 1989-2015.Cancer Med. 2018; 7: 2160-2171
- The impact of African ancestry on prostate cancer disparities in the Era of precision medicine.Genes (Basel). 2020; 11
- Highly penetrant hereditary cancer syndromes.Oncogene. 2004; 23: 6445-6470
- Familial risk and heritability of cancer among twins in nordic countries.JAMA. 2016; 315: 68-76
- Inherited DNA-repair gene mutations in men with metastatic prostate cancer.N Engl J Med. 2016; 375: 443-453
- Prevalence of germline variants in prostate cancer and implications for current genetic testing guidelines.JAMA Oncol. 2019; 5: 523-528
- Cancers associated with BRCA1 and BRCA2 mutations other than breast and ovarian.Cancer. 2015; 121: 269-275
- Prostate cancer incidence in males with Lynch syndrome.Genet Med. 2014; 16: 553-557
- Inherited mutations in men undergoing multigene panel testing for prostate cancer: emerging implications for personalized prostate cancer genetic evaluation.JCO Precision Oncol. 2017; : 1-17
- Rare germline mutations in the BRCA2 gene are associated with early-onset prostate cancer.Br J Cancer. 2007; 97: 826-831
- Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer.J Clin Oncol. 2013; 31: 1748-1757
- Risk of prostate cancer in lynch syndrome: a systematic review and meta-analysis.Cancer Epidem Biomar. 2014; 23: 437-449
- Elevated risk of prostate cancer among men with Lynch syndrome.J Clin Oncol. 2013; 31: 1713-1718
- Germline homeobox B13 (HOXB13) G84E mutation and prostate cancer risk in European descendants: a meta-analysis of 24 213 cases and 73 631 controls.Eur Urol. 2013; 64: 173-176
National Comprehensive Cancer Network. Prostate Cancer (Version 2.2021). https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf. Accessed March 29, 2021
National Comprehensive Cancer Network. Prostate Cancer Early Detection (1.2021). https://www.nccn.org/professionals/physician_gls/pdf/prostate_detection.pdf. Accessed March 29, 2021
- Germline mutations in ATM and BRCA1/2 are associated with grade reclassification in men on active surveillance for prostate cancer.Eur Urol. 2019; 75: 743-749
- DNA-repair defects and olaparib in metastatic prostate cancer.N Engl J Med. 2015; 373: 1697-1708
- Rucaparib in men with metastatic castration-resistant prostate cancer harboring a BRCA1 or BRCA2 gene alteration.J Clin Oncol. 2020; 38: 3763-3772
- Platinum-based chemotherapy in metastatic prostate cancer with DNA repair gene alterations.JCO Precis Oncol. 2020; 4: 355-366
- Pembrolizumab in men with heavily treated metastatic castrate-resistant prostate cancer.Cancer Med. 2019; 8: 4644-4655
- Diversity of enrollment in prostate cancer clinical trials: current status and future directions.Cancer Epidemiol Biomarkers Prev. 2020; 29: 1374-1380
- Racial/ethnic disparities in genomic sequencing.JAMA Oncol. 2016; 2: 1070-1074
- Genome-wide association studies in Africans and African Americans: expanding the framework of the genomics of human traits and disease.Public Health Genomics. 2015; 18: 40-51
- Clinical use of current polygenic risk scores may exacerbate health disparities.Nat Genet. 2019; 51: 584-591
- A review of prostate cancer Genome-Wide Association Studies (GWAS).Cancer Epidemiol Biomarkers Prev. 2018; 27: 845-857
- Prostate cancer susceptibility in men of African ancestry at 8q24.J Natl Cancer Inst. 2016; 108: 1-5
- Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men.Proc Natl Acad Sci U S A. 2006; 103: 14068-14073
- A common variant associated with prostate cancer in European and African populations.Nat Genet. 2006; 38: 652-658
- Genetic polymorphism and prostate cancer aggressiveness: a case-only study of 1,536 GWAS and candidate SNPs in African-Americans and European-Americans.Prostate. 2013; 73: 11-22
- Vitamin D receptor genetic polymorphisms are associated with PSA level, Gleason score and prostate cancer risk in African-American men.Anticancer Res. 2015; 35: 1549-1558
- Whole-exome sequencing of over 4100 men of African ancestry and prostate cancer risk.Hum Mol Genet. 2016; 25: 371-381
- A genetic score can identify men at high risk for prostate cancer among men with prostate-specific antigen of 1-3 ng/ml.Eur Urol. 2014; 65: 1184-1190
- Prostate cancer risk prediction using a polygenic risk score.Sci Rep. 2020; 10: 17075
- Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer.J Clin Oncol. 2013; 31: 1748-1757
- Germline mutations in ATM and BRCA1/2 distinguish risk for lethal and indolent prostate cancer and are associated with early age at death.Eur Urol. 2017; 71: 740-747
- Ethnic disparities among men with prostate cancer undergoing germline testing.Urol Oncol. 2020; 38 (80 e81-80 e87)
- Inherited DNA-repair gene mutations in African American men with prostate cancer.Oncotarget. 2020; 11: 440-442
- Rare germline mutations in African American men diagnosed with early-onset prostate cancer.Prostate. 2018; 78: 321-326
- Rare germline mutations in the BRCA2 gene are associated with early-onset prostate cancer.Br J Cancer. 2007; 97: 826-831
- Increased frequency of germline BRCA2 mutations associates with prostate cancer metastasis in a racially diverse patient population.Prostate Cancer Prostatic Dis. 2019; 22: 406-410
- Pathogenic variants in cancer predisposition genes and prostate cancer risk in men of African ancestry.JCO Precis Oncol. 2020; 4: 32-43
- Integrative clinical genomics of advanced prostate cancer.Cell. 2015; 162: 454
- Germline sequencing DNA repair genes in 5,545 men with aggressive and non-aggressive prostate cancer.J Natl Cancer Inst. 2021; 113: 616-625
- Response to olaparib in a PALB2 germline mutated prostate cancer and genetic events associated with resistance.Cold Spring Harb Mol Case Stud. 2019; 5: 1-9
- CHEK2 mutation and risk of prostate cancer: a systematic review and meta-analysis.Int J Clin Exp Med. 2015; 8: 15708-15715
- Updated insights into genetic contribution to prostate cancer predisposition: focus on HOXB13.Can J Urol. 2019; 26: 12-13
- HOXB13 is a susceptibility gene for prostate cancer: results from the International Consortium for Prostate Cancer Genetics (ICPCG).Human Genetics. 2013; 132: 5-14
- Elevated risk of prostate cancer among men with Lynch syndrome.J Clin Oncol. 2013; 31: 1713-1718
- Genetic testing for hereditary prostate cancer: current status and limitations.Cancer. 2018; 124: 3105-3117
- Inequities in multi-gene hereditary cancer testing: lower diagnostic yield and higher VUS rate in individuals who identify as Hispanic, African or Asian and Pacific Islander as compared to European.Fam Cancer. 2019; 18: 465-469
- Diversity and inclusion in genomic research: why the uneven progress?.J Community Genet. 2017; 8: 255-266
- Under the shadow of Tuskegee: African Americans and health care.Am J Public Health. 1997; 87: 1773-1778
- Community leaders' perspectives on engaging African Americans in biobanks and other human genetics initiatives.J Community Genet. 2013; 4: 483-494
- Strategies for enrollment of African Americans into cancer genetic studies.J Cancer Educ. 2015; 30: 108-115
- Barriers to the use of genetic testing: a study of racial and ethnic disparities.Genet Med. 2009; 11: 655-662
- Intentions to donate to a biobank in a national sample of African Americans.Public Health Genomics. 2014; 17: 173-182
- Factors affecting research participation in African American college students.Fam Med. 2008; 40: 46-51
American Urological Association. AUA 2019 Annual Census.https://www.auanet.org/research/research-resources/aua-census/census-results. Published 2019. Accessed April 3, 2021.
- Minority, underrepresented groups working to bring diversity to research: All of Us partners engage communities.The Nation's Health. 2019; 48: 17
- Assessing the effectiveness of the National Comprehensive Cancer Network genetic testing guidelines in identifying African American breast cancer patients with deleterious genetic mutations.Breast Cancer Res Treat. 2019; 178: 151-159
- Characterizing genetic risk at known prostate cancer susceptibility loci in African Americans.PLoS Genet. 2011; 7e1001387
- Genetic ancestry and prostate cancer susceptibility SNPs in Puerto Rican and African American men.Prostate. 2017; 77: 1118-1127
- 8q24 risk alleles in West African and Caribbean men.Prostate. 2012; 72: 1366-1373
- Prostate cancer risk associated loci in African Americans.Cancer Epidemiol Biomarkers Prev. 2009; 18: 2145-2149
- A comprehensive resequence-analysis of 250 kb region of 8q24.21 in men of African ancestry.Prostate. 2014; 74: 579-589
- Homologous repair of DNA damage and tumorigenesis:the BRCA connection.Oncogene. 2002; 21: 8981-8993
- The ATM protein kinase: regulating the cellular response to genotoxic stress, and more.Nat Rev Mol Cell Biol. 2013; 14: 197-210
- PALB2 functionally connects the breast cancer susceptibility proteins BRCA1 and BRCA2.Mol Cancer Res. 2009; 7: 1110
- CHEK2 Germline Variants in Cancer Predisposition: Stalemate Rather than Checkmate.Cells. 2020; 9: 2675
- Developmental patterning. The Hox code out on a limb.Curr Biol. 1994; 4: 1135-1137
- Germline mutations in HOXB13 and prostate-cancer risk.N Engl J Med. 2012; 366: 141-149
- Association between germline HOXB13 G84E mutation and risk of prostate cancer.J Natl Cancer Inst. 2012; 104: 1260-1262
Article info
Publication history
Published online: August 25, 2021
Accepted:
August 12,
2021
Received:
March 29,
2021
Footnotes
Declaration of Interests: The authors report the following financial interests.
KB: Stratify genomics – consultant.
Funding: None.
Identification
Copyright
© 2021 Elsevier Inc. All rights reserved.
