Influence of family history on penetrance of hereditary cancers in a population setting.
Leigh Jackson et al. EClinicalMedicine 2023 11 102159
From the abstract: "Women with a pathogenic BRCA1 or BRCA2 variant had an increased risk of breast cancer that was higher in those with a first-degree family history (relative hazard 10.3 and 7.8, respectively) than those without (7.2 and 4.7). Penetrance to age 60 was also higher in those with a family history (44.7%, CI 32.2-59.3 and 24.1%, CI 17.5-32.6) versus those without (22.8%, CI 15.9-32.0 and 17.9%, CI 13.8-23.0). A similar pattern was seen in Lynch syndrome: individuals with a pathogenic MLH1, MSH2 or MSH6 variant had an increased risk of colorectal cancer that was significantly higher in those with a family history (relative hazard 35.6, 48.0 and 9.9) "
Combined population genomic screening for three high-risk conditions in Australia: a modelling study
P Lacaze et al, e Clin Medicine, November 2023
From the abstract: "This modeling study assessed the impact of offering combined genomic screening for hereditary breast and ovarian cancer, Lynch syndrome and familial hypercholesterolaemia to all young adults in Australia, compared with the current practice of clinical criteria-based testing for each condition separately. Our findings suggest that offering combined genomic screening for high-risk conditions to young adults would be cost-effective in the Australian public healthcare system, at currently realistic testing costs. "
Neoplasia risk in patients with Lynch syndrome treated with immune checkpoint blockade.
Emily C Harrold et al. Nat Med 2023 10 (10) 2458-2463
From the abstract: "Metastatic and localized mismatch repair-deficient (dMMR) tumors are exquisitely sensitive to immune checkpoint blockade (ICB). The ability of ICB to prevent dMMR malignant or pre-malignant neoplasia development in patients with Lynch syndrome (LS) is unknown. Of 172 cancer-affected patients with LS who had received =1 ICB cycles, 21 (12%) developed subsequent malignancies after ICB exposure, 91% (29/32) of which were dMMR, with median time to development of 21?months (interquartile range, 6–38). "
Public attitudes challenge clinical practice on genetic risk disclosure in favour of healthcare-provided direct dissemination to relatives
A Rosen et al, EJHG, July 20, 2023
Germline genetic testing often has implications not only for the individual patient but also for their genetic relatives. This is especially true for high-penetrance pathogenic variants associated with conditions such as familial hypercholesterolemia and hereditary cancer risk syndromes like Lynch syndrome and the hereditary breast and ovarian cancer syndrome. For these conditions, targeted prevention programs are available, and cascade screening is cost-effective. It is therefore highly relevant to find effective strategies to disclose information from the genetic investigation to healthy relatives at risk. Informing relatives at risk enables equitable access to pre-test genetic counselling and a possibility for them to make an informed decision about genetic testing as well as prevention.