Batra Atul, Cockburn Jessica G, Mittal Abhenil, Bernardino Rui M, Sildva Tiiu, Wettstein Marian Severin, Seth Amlesh, Nayak Brusabhanu, Bakhshi Sameer, Sahoo Ranjit K, Kumar Akash, Jain Rishabh, Kaushal Seema, Singh Mayank, Gund Sneha, Chowdhary Sunakshi, Lakhani Karina, Patel Krishna, Kim Raymond H, Akbari Mohammad R, Fleshner Neil Eric
Department of Medical Oncology, Dr BRA-IRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON.
JCO Precis Oncol. 2025 Jul;9:e2500130. doi: 10.1200/PO-25-00130. Epub 2025 Jul 10.
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 .
尽管前列腺癌总体预后良好，但转移性疾病仍无法治愈。此外，一部分高危或转移性疾病患者可能在已知的前列腺癌相关基因中至少携带一种种系变异。由于队列选择和测序策略的差异，全球人群中种系变异的患病率尚不清楚。
采用全外显子组测序（WES）方法，对一组来自印度的转移性前列腺癌患者的种系变异进行探索。总共前瞻性且连续招募了276名在印度新德里全印度医学科学研究所接受治疗的个体。对血液样本进行标准的WES和生物信息学分析，以确定致病性和可能致病性（PV/LPV）前列腺癌变异的患病率，然后评估其与临床特征的相关性。
在与前列腺癌相关的8个基因中，共11%的个体检测到PV/LPV，最常见于BRCA2（3.98%）。该分布反映了先前其他全球队列发表的结果，尽管特定变异的患病率频率略有不同。未检测到变异状态与临床特征之间的关系，尽管对更大队列的分析可能会有不同结果。
这些结果表明，在印度背景下，针对转移性疾病患者遵循现有指南进行前列腺癌种系筛查时，变异检测频率相似。总之，由于基因差异（即变异），一些男性比其他男性更易患晚期转移性前列腺癌。本研究观察了一组印度患者中这些变异的数量。我们发现该组变异数量与世界其他地区相似，包括在一个名为 的基因中发现的更多变异。
