Laura Gross

Assessing the Clinical Role of Genetic Markers of Early-Onset Prostate Cancer among High-Risk Men Enrolled in Prostate Cancer Early Detection

Background: Men with familial prostate cancer and African American men are at risk for developing prostate cancer at younger ages. Genetic markers predicting early-onset prostate cancer may provide clinically useful information to guide screening strategies for high-risk men. We evaluated clinical information from six polymorphisms associated with early-onset prostate cancer in a longitudinal cohort of high-risk men enrolled in prostate cancer early detection with significant African American participation. Methods: Eligibility criteria include ages 35 to 69 with a family history of prostate cancer or African American race. Participants undergo screening and biopsy per study criteria. Six markers associated with early-onset prostate cancer [rs2171492 (7q32), rs6983561 (8q24), rs10993994 (10q11), rs4430796 (17q12), rs1799950 (17q21), and rs266849 (19q13)] were genotyped. Cox models were used to evaluate time to prostate cancer diagnosis and prostate-specific antigen (PSA) prediction for prostate cancer by genotype. Harrells concordance index was used to evaluate predictive accuracy for prostate cancer by PSA and genetic markers. Results: Four hundred and sixty participants with complete data and ≥1 follow-up visit were included. Fifty-six percent were African American. Among African American men, rs6983561 genotype was significantly associated with earlier time to prostate cancer diagnosis (P = 0.005) and influenced prediction for prostate cancer by the PSA (P < 0.001). When combined with PSA, rs6983561 improved predictive accuracy for prostate cancer compared with PSA alone among African American men (PSA = 0.57 vs. PSA + rs6983561 = 0.75, P = 0.03). Conclusions: Early-onset marker rs6983561 adds potentially useful clinical information for African American men undergoing prostate cancer risk assessment. Further study is warranted to validate these findings. Impact: Genetic markers of early-onset prostate cancer have potential to refine and personalize prostate cancer early detection for high-risk men. Cancer Epidemiol Biomarkers Prev; 21(1); 53–60. ©2011 AACR.

Interest in genomic SNP testing for prostate cancer risk: a pilot survey.

BackgroundAdvancements in genomic testing have led to the identification of single nucleotide polymorphisms (SNPs) associated with prostate cancer. The clinical utility of SNP tests to evaluate prostate cancer risk is unclear. Studies have not examined predictors of interest in novel genomic SNP tests for prostate cancer risk in a diverse population.MethodsConsecutive participants in the Fox Chase Prostate Cancer Risk Assessment Program (PRAP) (n = 40) and unselected men from surgical urology clinics (n = 40) completed a one-time survey. Items examined interest in genomic SNP testing for prostate cancer risk, knowledge, impact of unsolicited findings, and psychosocial factors including health literacy.ResultsKnowledge of genomic SNP tests was low in both groups, but interest was higher among PRAP men (p < 0.001). The prospect of receiving unsolicited results about ancestral genomic markers increased interest in testing in both groups. Multivariable modeling identified several predictors of higher interest in a genomic SNP test including higher perceived risk (p = 0.025), indicating zero reasons for not wanting testing (vs ≥1 reason) (p = 0.013), and higher health literacy (p = 0.016).ConclusionsKnowledge of genomic SNP testing was low in this sample, but higher among high-risk men. High-risk status may increase interest in novel genomic tests, while low literacy may lessen interest.

Validation of association of genetic variants at 10q with prostate‐specific antigen (PSA) levels in men at high risk for prostate cancer

To validate six previously identified markers among men at increased risk of prostate cancer (African‐American men and those with a family history of prostate cancer) enrolled in the Prostate Cancer Risk Assessment Program (PRAP), a prostate cancer screening study.

Inherited Mutations in Men Undergoing Multigene Panel Testing for Prostate Cancer: Emerging Implications for Personalized Prostate Cancer Genetic Evaluation

PurposeMultigene panels are commercially available for the evaluation of prostate cancer (PCA) predisposition, which necessitates tailored genetic counseling (GC) for men. Here we describe emerging results of Genetic Evaluation of Men, prospective multigene testing study in PCA to inform personalized genetic counseling, with emerging implications for referrals, cancer screening, and precision therapy.Patients and MethodsEligibility criteria for men affected by or at high risk for PCA encompass age, race, family history (FH), and PCA stage/grade. Detailed demographic, clinical, and FH data were obtained from participants and medical records. Multigene testing was conducted after GC. Mutation rates were summarized by eligibility criteria and compared across FH data. The 95% CI of mutation prevalence was constructed by using Poisson distribution.ResultsOf 200 men enrolled, 62.5% had PCA. Eleven (5.5%; 95% CI, 3.0% to 9.9%) had mutations; 63.6% of mutations were in DNA repair genes. FH of breast cancer was si...

Validation of Association of Genetic Variants at 10q with PSA Levels in Men at High Risk for Prostate Cancer

To validate six previously identified markers among men at increased risk of prostate cancer (African‐American men and those with a family history of prostate cancer) enrolled in the Prostate Cancer Risk Assessment Program (PRAP), a prostate cancer screening study.

Understanding of multigene test results among males undergoing germline testing for inherited prostate cancer: Implications for genetic counseling

Genetic testing (GT) for prostate cancer (PCA) is rising, with limited insights regarding genetic counseling (GC) needs of males. Genetic Evaluation of Men (GEM) is a prospective multigene testing study for inherited PCA. Men undergoing GC were surveyed on knowledge of cancer risk and genetics (CRG) and understanding of personal GT results to identify GC needs.

Effects of a randomized trial comparing standard and enhanced counseling for men at high risk of prostate cancer as a function of race and monitoring style

Despite conflicting guidelines, a significant subset of high-risk men decide to undergo routine prostate cancer screening. Yet, there is a scarcity of available programs, and no studies evaluating interventions to support men in dealing with the psychosocial impact of screening. In this study, one of the first to explore the responses of high-risk men enrolling in a Prostate Cancer Risk Assessment Program (N = 128), patients underwent a prostate cancer risk counseling visit immediately followed by either a cognitive–affective preparation session designed to help them process the information they received or a general health education session. All men in this self-selected sample chose to participate in prostate cancer screening. Men were assessed 3 weeks and 6 months post-counseling. The impact of the enhanced counseling condition on knowledge, perceived risk, expectancies, and intrusive ideation was a function of racial and coping style group. Implications for tailored interventions to maximize preparedness for risk and screening counseling are discussed.

Validation of association of genetic variants at 10q with prostate-specific antigen (PSA) levels in men at high risk for prostate cancer: Genetic correction of PSA in men at high-risk for PCA

To validate six previously identified markers among men at increased risk of prostate cancer (African‐American men and those with a family history of prostate cancer) enrolled in the Prostate Cancer Risk Assessment Program (PRAP), a prostate cancer screening study.

Abstract B13: Lessons learned from implementing a prostate cancer risk assessment program for underserved high-risk men: The Prostate REACH Project

Background: Prostate cancer disproportionately affects Black men. Black men are 60% more likely to be diagnosed with prostate cancer and 2.4 times more likely to die from prostate cancer compared to White men. Therefore, prostate cancer risk assessment programs are important to assess risk, discuss risks and benefits of screening, and provide screening services. However, Black men may encounter barriers to participation in these programs such as lack of health insurance, difficulty with travel to clinic, and challenges with navigating the medical system. To address these barriers, the Prostate Cancer Risk, Education and Assessment in the Community with Help (REACH) project was developed as a community-based extension of a comprehensive prostate cancer risk assessment program (PRAP) at Fox Chase Cancer Center (FCCC). This is a pilot project to evaluate the feasibility and acceptability of a community-based risk assessment program. Methods: Developing the REACH project infrastructure included: 1) choosing a clinic site; 2) establishing patient access procedures; 3) establishing navigator services; 4) developing procedures for subsidy fund use; and 5) recruitment and promotion. Given the challenges of establishing a community site, we chose to utilize our mobile mammography van as the screening venue. Evaluation measures included recruitment and participation rates, utilization of patient navigation services, as well as patient satisfaction. A self-administered survey assessed the distance travelled to receive screening services, whether or not they utilized patient navigator services, the importance of having a community screening site in their decision to participate (5-point Likert scale), the importance of having a patient navigator to assist (5-point Likert scale), satisfaction with any patient navigation services provided (5-point Likert scale), and overall satisfaction with the program (5-point Likert scale). Results: As of April 2011, 35 men have called regarding the program. Of these, 20 were eligible and 13 men have received prostate cancer risk assessment services through Prostate REACH. Twelve participants were screened on the van and one patient at the FCCC PRAP clinic. The majority of participants are Black men. The mean age at enrollment is 48.6 years (range 36–64 years). Approximately 69% of participants received patient navigation services. The patient navigator contacted each participant on average three times to address barriers. Insurance issues were the most common barrier (88%) addressed by the navigator. Support issues (emotional and caregiver) also were addressed. All participants completed the user survey following their screening. Nearly 70% of men travelled five miles or less to be screened, and 54% reported that they utilized patient navigation services (slightly under the 69% who actually did receive some navigation). The majority of participants thought having a community screening location and a patient navigator was important for participation. The majority of participants were quite a bit to extremely satisfied with the overall REACH program (Mean=4.85, SD=0.38). Conclusions: The REACH experience highlights specific implementation challenges faced in expanding access to prostate cancer risk assessment to underserved men. Patient navigation services may be essential to participation among underserved populations. Future research should explore various recruitment strategies to increase participation. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B13.