BUFFALO, NY- August 26, 2024 – A new #editorial was #published in Oncotarget's Volume 15 on July 10, 2024, entitled, “Genotype matters: Personalized screening recommendations for germline CHEK2 variants.” Recognized as a moderate-risk gene, CHEK2—responsible for encoding the CHK2 protein, which plays a crucial role in the repair of DNA double-strand breaks—is associated with a 20–40% lifetime risk of breast cancer (BC) by age 85. While CHEK2 pathogenic variants (PVs) were previously linked to an increased risk of colorectal cancer (CRC), two recent studies have not observed this association. In their recent work, researchers Adela Rodriguez Hernandez, Rochelle Scheib, Judy E. Garber, Huma Q. Rana and Brittany L. Bychkovsky from Dana-Farber Cancer Institute and Harvard Medical School in Boston, found that a CHEK2 PV does not increase the CRC risk compared with controls (odds ratio 0.62 (0.51–0.76), p < .001). The cancer risks associated with CHEK2 PVs vary depending on the variant type, and risk management strategies should reflect this variability. The CHEK2 c.1100del is the most studied truncating variant and has been crucial to our understanding of the cancer phenotype. Cancer risks seem to be higher with truncating variants compared to missense variants. “In our study, we postulated that these differences were driven by three common low-risk (LR) missense variants: p.I157T, p.S428F, and p.T476M, all of which have a BC odds ratio of <1.4.” In summary, CHEK2 is recognized as a moderate-risk gene for breast cancer. Further large-scale, prospective studies are needed to clarify its potential associations with prostate, kidney, and thyroid cancers, as well as to establish appropriate screening measures. DOI - https://doi.org/10.18632/oncotarget.28604 Correspondence to - Brittany L. Bychkovsky - brittany_bychkovsky@dfci.harvard.edu Video short - https://www.youtube.com/watch?v=KYHCdGz8c3I Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28604 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, CHEK2, pathogenic or likely pathogenic variants, germline About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM