{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T20:45:30Z","timestamp":1786653930425,"version":"build-2736575974"},"reference-count":40,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"8","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Glob Oncol"],"published-print":{"date-parts":[[2026,8]]},"abstract":"\n PURPOSE<\/jats:title>\n \n Homologous recombination repair (HRR) pathway defects are critical drivers of hereditary cancers, yet population-specific prevalence data from India remain limited. Current testing practices disproportionately focus on\n BRCA1\/2<\/jats:italic>\n , potentially underidentifying patients with other HRR gene variants who could benefit from targeted therapies.\n <\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n A retrospective observational cohort study was conducted, analyzing 950 consecutive patients who underwent next generation sequencing-based germline testing at the Cancer Genetics Clinic, Mahamana Pandit Madanmohan Malaviya Cancer Centre, Varanasi. The core HRR panel included\n BRCA1<\/jats:italic>\n ,\n BRCA2<\/jats:italic>\n ,\n PALB2<\/jats:italic>\n ,\n RAD51C<\/jats:italic>\n ,\n RAD51D<\/jats:italic>\n ,\n ATM<\/jats:italic>\n ,\n CHEK2<\/jats:italic>\n ,\n BRIP1<\/jats:italic>\n ,\n BARD1<\/jats:italic>\n ,\n RAD50<\/jats:italic>\n ,\n NBN<\/jats:italic>\n ,\n MRE11<\/jats:italic>\n , and\n FANCC<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Of 950 patients analyzed, 364 (38.3%) harbored variants in HRR genes, with 266 (28%) carrying pathogenic\/likely pathogenic (P\/LP) variants\n . BRCA1<\/jats:italic>\n was the most frequently altered gene (182\/266, 68.4% of P\/LP variants), followed by\n BRCA2<\/jats:italic>\n (37\/266, 13.9%). Combined BRCA1\/2 genetic variants accounted for 219\/266 (82.3 17%) of all P\/LP variants. Non-\n BRCA<\/jats:italic>\n HRR genes contributed 47\/266 (17.6%) P\/LP variants, with\n PALB2<\/jats:italic>\n being the most common (14\/266, 5.2%). The study identified 98 variants of uncertain significance across the HRR genes.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSION<\/jats:title>\n \n This large Indian cohort demonstrates a high prevalence of HRR gene alterations, with significant contribution from non-\n BRCA<\/jats:italic>\n genes. These findings support the implementation of comprehensive HRR gene panels in Indian populations and highlight the therapeutic implications for poly (ADP-ribose) polymerase inhibitor and platinum-based treatment strategies.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1200\/go-25-00640","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T19:59:14Z","timestamp":1786651154000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Uncovering Hereditary Risk: Germline Homologous Recombination Repair Variant Spectrum in a Large North Indian Cancer Cohort (INSIGHT-HRR)"],"prefix":"10.1200","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6006-2631","authenticated-orcid":true,"given":"Akhil","family":"Kapoor","sequence":"first","affiliation":[{"name":"Medical Oncology, Mahamana Pandit Madanmohan Malaviya Cancer Centre & Homi Bhabha Cancer Hospital, Tata Memorial Centre, Homi Bhabha National 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