Incomplete Penetrance of Population-Based Genetic Screening Results in Electronic Health Record
G Elhanan et al, Frontiers in Genetics, April 2022
The clinical value of population-based genetic screening projects depends on the actions taken on the findings. The Healthy Nevada Project (HNP) is an all-comer genetic screening and research project based in northern Nevada. HNP participants with CDC Tier 1 findings of hereditary breast and ovarian cancer syndrome (HBOC), Lynch syndrome (LS), or familial hypercholesterolemia (FH) are notified and provided with genetic counseling. However, the HNP subsequently takes a “hands-off” approach: it is the responsibility of notified participants to share their findings with their healthcare providers, and providers are expected to implement the recommended action plans.
Paired Tumor-Germline Testing as a Driver in Better Cancer Care
JW Henson et al, JAMA Network Open, May 20, 2022
Paired tumor-germline testing can lead to better treatment choices. Hereditary cancer syndromes are caused by inactivated tumor suppressor genes. By comparison, activated oncogenes are poorly tolerated during embryonic development. Variant tumor suppressor genes and their inactive protein products are more challenging to target than are activated oncogenes. Attention thus turns from the gene itself to the aberrant downstream molecular pathway and subsequent effects of the pathway. Two notable examples are the use of checkpoint inhibitors to target high tumor mutation burdens from tumors related to a defective mismatch repair pathway (ie, Lynch syndrome when originating in germline) and poly adenosine diphosphate ribose polymerase inhibitors to exploit single-strand breaks from tumors related to the homologous repair/BRCA pathway (ie, hereditary breast and ovarian cancer syndrome when originating in germline).
Lynch syndrome; towards more personalized management?
J Llach et al, Best Practice & Research Clinical Gastroenterology, March 2022
Lynch syndrome is the most common inherited cause of colorectal (lifetime risk up to 70%) and endometrial cancer. The diagnosis of Lynch syndrome facilitates preventive measures aimed at reducing the incidence and mortality of cancer. Colonoscopic surveillance for colorectal cancer, aspirin, and prophylactic hysterectomy and bilateral salpo-oopherectomy for endometrial and/or ovarian cancer have demonstrated to effectively reduce cancer mortality in this population. However, the lifetime risk of each cancer in people with Lynch syndrome is gene-specific and may be modified by environmental factors. Furthermore, the benefits of surveillance strategies need to be balanced against the risk of over-diagnosis and be supported by evidence of improved outcomes
New generation of cancer-preventing vaccines could wipe out tumors before they form
J Kaiser, Science, April 7, 2022
Researchers are trying out several vaccine strategies. Some use so-called tumor antigens, molecular markers that are scarce on healthy cells but plentiful on cancer cells. The Lynch syndrome vaccine instead targets “neoantigens,” a potent type of antigen only found on tumor cells. Some deploy just a single antigen whereas others use a large number, in a bid to broadly shield against cancer. The best approach is unclear, and developers also face the difficult challenge of measuring success without waiting decades for healthy people to develop cancers.