Prevalence of pathogenic germline variants and indications for testing in a diverse community-based endometrial cancer cohort.

Germline pathogenic variants in homologous recombination deficiency genes (including BRCA1, BRCA2, ATM, BRIP1, RAD51C, RAD51D) and Lynch syndrome genes (including MSH6, PMS2, MLH1, EPCAM)

This community-based cohort study of diverse patients covered 10,233 women diagnosed with endometrial cancer between 2016 and 2022, of whom 1487 (14.5%) underwent germline testing. Among them, 251 (16.9%) carried a pathogenic variant: 64 (4.3%) related to homologous recombination deficiency and 134 (9.0%) to Lynch syndrome. After propensity score weighting, the estimated prevalence in the whole cohort was 11.9% (95% CI 9.6-14.6), including 1.7% Lynch syndrome and 4.7% homologous recombination deficiency-related variants. Testing at diagnosis identified 74% of carriers, including 89.6% of those with a Lynch variant but only 54.7% of those with a homologous recombination deficiency-related variant. Prevalence did not differ by race, but Lynch variants were more common in Asian patients.

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

The gap between 9.0% Lynch syndrome among tested patients and the 1.7% estimated in the whole cohort shows how much the crude prevalence overestimates risk when only 14.5% of women are tested; propensity score weighting corrects this bias for measured variables, not for others. Testing at diagnosis captures only 54.7% of homologous recombination deficiency-related variants, which questions the timing and indications of testing for these genes. The retrospective design and community recruitment do not limit the scope here: it is the proportion of women tested that sets the limits of the estimate.

Analysis by Dr Thibaut Benquey