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

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.

A global approach to improving penile cancer care.

Rare tumours such as penile carcinoma have been largely neglected by the urology scientific community in favour of more common - and, therefore, more easily fundable - diseases. Nevertheless, penile cancer represents a rising burden for health-care systems around the world, because a lack of widespread expertise, ineffective centralization of care and absence of research funds have hampered our ability to improve the global care of these patients. Moreover, a dichotomy has arisen in the field of penile cancer, further impeding care: the countries that are mainly supporting research on this topic through the development of epidemiological studies and design of clinical trials are not the countries that have the highest prevalence of the disease. This situation means that randomized controlled trials in developed countries often do not meet the minimum accrual and are intended to close before reaching their end points, whereas trials are almost completely absent in those areas with the highest disease prevalence and probability of successful recruitment, such as Africa, South America and South Asia. The scientific and organizational inaction that arises owing to this mismatch translates into a burdensome cost for our patients. A global effort to gather experts and pull together scientific data from around the world may be the best way to boost clinical research, to change clinical practice and, ultimately, to improve care for patients and their families.