A Decade of Hereditary Cancer Genetic Testing Results in Asian Indian population: Retrospective Study.

Germline multigene NGS panels complemented by MLPA, revealing a recurrent BRCA1 founder variant (c.68_69delAG) and predominance of MMR genes (MLH1, MSH2, MSH6) in colorectal and endometrial cancers.

Large datasets describing germline variant distribution across India have been lacking. This retrospective analysis covers 23,070 individuals tested at a Bangalore laboratory between 2016 and 2025 with validated multigene NGS panels, plus MLPA for copy number variant detection in a subset, grouped as breast (n = 10,486), ovarian (n = 3,990), colorectal (n = 1,275), prostate (n = 765) and endometrial cancer (n = 541) and asymptomatic individuals (n = 2,775). Overall diagnostic yield was 23.85%, highest in colorectal (42%) and ovarian cancer (31.6%), followed by endometrial (22.6%), breast (20.2%) and prostate cancer (8.6%), reaching 18.9% in asymptomatic individuals with a positive family history and 24.2% in breast cancers diagnosed at 50 years or younger. BRCA1 and BRCA2 predominated in breast and ovarian cancer, MMR genes (MLH1, MSH2, MSH6) in colorectal and endometrial cancer and BRCA2 in prostate cancer, with the BRCA1 founder variant c.68_69delAG identified in 358 individuals, ahead of a canonical splice-site variant c.5074+1G>A (n = 123) and a nonsense variant c.3607C>T (n = 44). Reanalysis of variants of uncertain significance and unsolved cases raised the yield by roughly 5 percentage points on average, and the decline in yield with increasing age leads the authors to favour universal over guideline-based testing.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

What this cohort specifically adds is not the overall yield, which is expected for a referred population, but the demonstration that a handful of recurrent BRCA1 variants accounts for a substantial share of positive results, opening the way to a cheap targeted first-line test in India and the South Asian diaspora before full panel testing. The caveat is methodological: these are commercial laboratory data without verified phenotype or clinical follow-up and with major referral bias, so the case for universal testing rests on a simple decline in yield with age rather than on a comparison of strategies. The 5-point gain from reanalysis of variants of uncertain significance is the figure most directly transferable to our own practice.

Analysis by Dr Thibaut Benquey