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

Abstract

Background Men with familial prostate cancer (PCA) and African American men are at risk for developing PCA at younger ages. Genetic markers predicting early-onset PCA may provide clinically useful information to guide screening strategies for high-risk men. We evaluated clinical information from six polymorphisms associated with early-onset PCA in a longitudinal cohort of high-risk men enrolled in PCA early detection with significant African American participation. Methods Eligibility criteria include ages 35–69 with a family history of PCA or African American race. Participants undergo screening and biopsy per study criteria. Six markers associated with early-onset PCA (rs2171492 (7q32), rs6983561 (8q24), rs10993994 (10q11), rs4430796 (17q12), rs1799950 (17q21), and rs266849 (19q13)) were genotyped. Cox models were used to evaluate time to PCA diagnosis and PSA prediction for PCA by genotype. Harrell’s concordance index was used to evaluate predictive accuracy for PCA by PSA and genetic markers. Results 460 participants with complete data and ≥1 follow-up visit were included. 56% were African American. Among African American men, rs6983561 genotype was significantly associated with earlier time to PCA diagnosis (p=0.005) and influenced prediction for PCA by the PSA (p<0.001). When combined with PSA, rs6983561 improved predictive accuracy for PCA compared to 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 PCA risk assessment. Further study is warranted to validate these findings. Impact Genetic markers of early-onset PCA have potential to refine and personalize PCA early detection for high-risk men.

Racial differences in prostate cancer risk in young HIV-positive and HIV-negative men: a prospective cohort study

“…A recent study in the largest HIV cohort in North America found that while age at prostate cancer diagnosis was younger among HIV-infected subjects, the difference was not statistically significant (21); findings were inconclusive with respect to young-onset prostate cancer in groups by HIV status because age was examined in 10-year bins rather than comparing age of young-onset prostate cancer cases by HIV status. Young-onset prostate cancers diagnosed before age 55 are biologically and genetically distinct compared to prostate cancers diagnosed in older men (8, 22). Moreover, high-grade prostate cancers occurring before age 55 have a higher risk of cancer-specific mortality (23).…”

“…Prostate cancer presents some unique challenges in HIV-infected populations, including higher cancer-specific mortality rates in comparison to HIV-uninfected populations (3) and lower rates of prostate-specific antigen (PSA) screening in subpopulations, including racial and sexual minorities (4–6). Major established risk factors in the general population are older age, African American race, and family history of prostate cancer (7, 8); modifiable risk factors include androgen supplement use and obesity (9, 10). The influence of HIV-related factors on prostate cancer risk remains poorly defined (11).…”

“…Moreover, high-grade prostate cancers occurring before age 55 have a higher risk of cancer-specific mortality (23). PSA screenings have greatly improved early detection of prostate cancers (7, 24), and detection rates of young-onset prostate cancer have increased from 2.3% of total prostate cancers diagnosed in the early-PSA era (1988 to early 1990s) to 9–10% in the post-PSA era (8, 25). American Cancer Society (ACS) guidelines suggest screening at age 40 for men with multiple first-degree relatives with prostate cancer, age 45 for African Americans and men with a single first-degree relative diagnosed with prostate cancer at age < 65, and age 50 for men at average risk.…”

“…African American men are also at higher risk for more aggressive tumors, and higher prostate cancer-related mortality. Management of prostate cancer risk and outcomes in African American men is influenced by racial disparities in health care access, surveillance, treatment, and survival (5, 6, 8, 26, 27). African American men are disproportionately represented among HIV-infected men, a population more vulnerable to health care disparities in comparison to uninfected men (5, 27, 28).…”

ecancermedicalscience

“…There is a wealth of evidence implicating 8q24 variant alleles in the development of CaP; some of which state that there is a higher frequency amongst those of African ancestry [42] and with earlier time to prostate cancer [43]. There are several other CaP susceptibility loci identified through genome-wide association studies, with inconsistencies between ethnic groups [44].…”