Prevalence of Suspected Hereditary Cancer Syndromes and Germline Mutations Among a Diverse Cohort of Probands Reporting a Family History of Prostate Cancer: Toward Informing Cascade Testing for Men.

BACKGROUND: Prostate cancer (PCa) is increasingly recognized as part of hereditary cancer syndromes (HCSs). HCS prevalence among diverse probands seeking genetic evaluation with PCa family history (FHx) has not been reported and has implications for cascade genetic testing. OBJECTIVE: To evaluate the rates of HCSs among probands reporting PCa FHx and germline mutations among probands. DESIGN, SETTING, AND PARTICIPANTS: A prospective genetic testing database queried for individuals with PCa FHx. Pedigrees analyzed for three HCSs: hereditary breast and ovarian cancer (HBOC), hereditary PCa, and Lynch syndrome. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Associations between HCS overall, and with plausible link to PCA FHx and race evaluated using Fisher\u27s exact test. Germline mutation rates described among probands with a suspicion of an HCS connected with PCa FHx. RESULTS AND LIMITATIONS: A total of 345 probands reported PCa FHx: 53 African American (AA) and 292 Caucasian (Wh). Overall, 220 probands (63.8%) met the criteria for at least one HCS with a potential link to PCa FHx (75.5% AA; 61.6% Wh). HBOC linked to PCa FHx was identified in a higher percentage of AA than Wh probands (90.2% vs 74.6%, p=0.04). Among probands who underwent genetic testing with any HCS potentially linked to PCa FHx (n=169), 19.5% had germline mutations identified; five AA probands had germline mutations (all in BRCA1/2), while 28 Wh probands had mutations in a spectrum of genes. CONCLUSIONS: A significant percentage of AA probands with PCa FHx meet the criteria for HCSs, with HBOC identified at the highest rate. Although limited in sample size, our findings implicate BRCA mutations in AA families with HCSs linked with PCa, underscoring the need for greater enrollment of AA participants in genetic studies. PATIENT SUMMARY: Hereditary cancer syndromes potentially linked to prostate cancer are common in patients reporting a family history of prostate cancer. African-American patients may need special attention with regard to testing for hereditary breast and ovarian cancer syndrome, which may impact men with prostate cancer in these families

Knowledge and practice regarding prostate cancer germline testing among urologists: Gaps to address for optimal implementation

BACKGROUND: Germline testing is recommended for all men with metastatic prostate cancer (PCa), and for some with localized PCa meeting specific histologic or family history criteria. Germline genetic evaluation has important implications for PCa prognosis and management, as well as implications for family members and cancer screening. Despite the importance of germline evaluation, its utilization in urologic practice is unknown. MATERIALS AND METHODS: We conducted a 32-item survey of U.S. urologists to examine knowledge of germline testing guidelines and practice patterns. It was shared through email to 6 American Urological Association sections, the Veterans Affairs Urology Mailgroup, and social media. RESULTS: Among 132 total respondents from diverse practice settings across the U.S., 12% perform germline testing, 44% refer to a genetic counselor, 11% do both, and 33% do not test/refer. Only 4% had formal education in genetics. While 98% ask about PCa family history, only 76% and 52% ask about breast and ovarian cancer. When presented with hypothetical case scenarios where germline testing is indicated, many respondents indicated they would not offer genetic counseling or testing. Younger age (p = 0,03), academic practice (p = 0.04), and specializing in PCa/oncology (p = 0.007) were significantly associated with performing or referring for germline testing. Specializing in PCa/oncology was significantly associated with recommending germline testing for all case scenarios involving metastatic PCa (p = 0.0009) CONCLUSION: Our results suggest significant gaps in knowledge of germline testing and alignment of practice with national guidelines among urologists. Germline testing education and facilitation of genetic evaluation in urologic practice is warranted

The effect of neighborhood social environment on prostate cancer development in black and white men at high risk for prostate cancer

INTRODUCTION: Neighborhood socioeconomic (nSES) factors have been implicated in prostate cancer (PCa) disparities. In line with the Precision Medicine Initiative that suggests clinical and socioenvironmental factors can impact PCa outcomes, we determined whether nSES variables are associated with time to PCa diagnosis and could inform PCa clinical risk assessment. MATERIALS AND METHODS: The study sample included 358 high risk men (PCa family history and/or Black race), aged 35-69 years, enrolled in an early detection program. Patient variables were linked to 78 nSES variables (employment, income, etc.) from previous literature via geocoding. Patient-level models, including baseline age, prostate specific antigen (PSA), digital rectal exam, as well as combined models (patient plus nSES variables) by race/PCa family history subgroups were built after variable reduction methods using Cox regression and LASSO machine-learning. Model fit of patient and combined models (AIC) were compared; p-values RESULTS: In combined models, nSES variables were significantly associated with time to PCa diagnosis. Workers mode of transportation and low income were significant in White men with a PCa family history. Homeownership (%owner-occupied houses with \u3e3 bedrooms) and unemployment were significant in Black men with and without a PCa family history, respectively. The 5-year predicted probability of PCa was higher in men with a high neighborhood score (weighted combination of significant nSES variables) compared to a low score (e.g., Baseline PSA level of 4ng/mL for men with PCa family history: White-26.7% vs 7.7%; Black-56.2% vs 29.7%). DISCUSSION: Utilizing neighborhood data during patient risk assessment may be useful for high risk men affected by disparities. However, future studies with larger samples and validation/replication steps are needed

Global Patterns of Prostate Cancer Incidence, Aggressiveness, and Mortality in Men of African Descent

Prostate cancer (CaP) is the leading cancer among men of African descent in the USA, Caribbean, and Sub-Saharan Africa (SSA). The estimated number of CaP deaths in SSA during 2008 was more than five times that among African Americans and is expected to double in Africa by 2030. We summarize publicly available CaP data and collected data from the men of African descent and Carcinoma of the Prostate (MADCaP) Consortium and the African Caribbean Cancer Consortium (AC3) to evaluate CaP incidence and mortality in men of African descent worldwide. CaP incidence and mortality are highest in men of African descent in the USA and the Caribbean. Tumor stage and grade were highest in SSA. We report a higher proportion of T1 stage prostate tumors in countries with greater percent gross domestic product spent on health care and physicians per 100,000 persons. We also observed that regions with a higher proportion of advanced tumors reported lower mortality rates. This finding suggests that CaP is underdiagnosed and/or underreported in SSA men. Nonetheless, CaP incidence and mortality represent a significant public health problem in men of African descent around the world

HOXB13 and other high penetrant genes for prostate cancer.

Cancer initiation and progression is the result of an accumulation of mutations in key tumor suppressor genes, mismatch repair genes, or oncogenes, which impact cancer cell growth, death, and differentiation. Mutations occurring in cancer tissue are termed somatic; whereas, heritable mutations that may be passed onto subsequent generations occur in germline DNA. It is these germline mutations that can lead to cancer family syndromes whereby family members carrying a deleterious germline mutation have an increased susceptibility to certain cancer phenotypes. Common features of hereditary cancer syndromes include early age-of-onset, multiple affected generations, rare tumor types, and/or multiple primary malignancies. Approximately, 5%-10% of all common cancers, including prostate cancer, have a hereditary component and are attributable to highly penetrant germline mutations.1 Across all cancer types, known cancer susceptibility syndromes number \u3e100; however, it is important to note that mutations in high-penetrance genes explain only a fraction of heritable cancers.2 Well-known examples of hereditary cancer syndromes include Lynch (HNPCC), Cowden (PHTS), Li-Fraumeni, and Hereditary Breast and Ovarian Cancer (HBOC) syndromes, which are attributable to mutations in mismatch repair genes, PTEN, p53, and BRCA1/2, respectively

HOXB13 and other high penetrant genes for prostate cancer

Cancer initiation and progression is the result of an accumulation of mutations in key tumor suppressor genes, mismatch repair genes, or oncogenes, which impact cancer cell growth, death, and differentiation. Mutations occurring in cancer tissue are termed somatic; whereas, heritable mutations that may be passed onto subsequent generations occur in germline DNA. It is these germline mutations that can lead to cancer family syndromes whereby family members carrying a deleterious germline mutation have an increased susceptibility to certain cancer phenotypes. Common features of hereditary cancer syndromes include early age-of-onset, multiple affected generations, rare tumor types, and/or multiple primary malignancies. Approximately, 5%–10% of all common cancers, including prostate cancer, have a hereditary component and are attributable to highly penetrant germline mutations.1 Across all cancer types, known cancer susceptibility syndromes number >100; however, it is important to note that mutations in high-penetrance genes explain only a fraction of heritable cancers.2 Well-known examples of hereditary cancer syndromes include Lynch (HNPCC), Cowden (PHTS), Li-Fraumeni, and Hereditary Breast and Ovarian Cancer (HBOC) syndromes, which are attributable to mutations in mismatch repair genes, PTEN, p53, and BRCA1/2, respectively.

Exploring Asian Indian and Pakistani Views about Cancer and Participation in Cancer Research: An Assessment of a Culturally Tailored Educational Intervention

This study was designed to deliver a culturally tailored educational intervention to improve knowledge, attitudes, and perceptions about cancer risk and preventive screening routines within the Asian Indian and Pakistani (AIP) population in the United States. Within this population, cancer is a leading cause of mortality yet screening rates remain low compared to other racial and ethnic groups. In addition, this sub-group has been largely underrepresented in clinical research. Twenty-nine participants were recruited to participate in a longitudinal survey that assessed changes in knowledge, attitudes, and perceptions of cancer risk and screenings over three data collection points (baseline, endpoint, and follow-up) after the delivery of an educational intervention. Data was analyzed for means, frequencies, and differences using SPSS. Only those that completed surveys at all three-time points were included in analysis. Twenty-three participants, 12 female and 10 male participants of AIP descent, averaging 46 (±11.93) years of age, completed the study. While there was no significant improvement in overall knowledge, participants showed significant improvement in knowledge of when screening for breast cancer should begin (