Prostate-Related Germline Variant Frequencies Detected in a Cohort of Men With Metastatic Prostate Cancer in Northern...

Although prostate cancer is generally associated with favorable outcomes, metastatic disease remains incurable. Additionally, a subset of individuals with high-risk or metastatic disease are likely to harbor at least one germline variant in known prostate cancer association genes. Because of differences in cohort selection and sequencing strategies, the prevalence of germline variants in global populations is unclear.

A whole-exome sequencing (WES) approach was used to explore germline variants in a cohort of patients with metastatic prostate cancer from India. In total, 276 individuals treated at the All India Institute of Medical Sciences in New Delhi, India, were prospectively and consecutively recruited. Blood specimens underwent standard WES and bioinformatic analysis to determine the prevalence of pathogenic and likely pathogenic (PV/LPV) prostate cancer variants, which were then assessed for associations with clinical features.

In total, PV/LPVs were detected in 11% of individuals across eight genes linked to prostate cancer, most frequently in BRCA2 (3.98%). The distribution reflects previously published findings from other global cohorts, although frequencies in the prevalence of specific variants differ slightly. No relationship between variant status and clinical features were detected, although analysis of a larger cohort may show otherwise.

These results indicate that germline screening for prostate cancer following existing guidelines yield similar variant detection frequencies when focusing on individuals with metastatic disease in the Indian context. In summary, some men are more likely to develop an advanced form of metastatic prostate cancer than others because of differences in their genes, known as variants. This study looked at the how many of these variants are in a group of patients from India. We found that the number of variants in this group was similar to those from other parts of the world, including more found in a gene called BRCA2.