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A recent study, conducted by researchers at the Johns Hopkins Kimmel Cancer Center, the Johns Hopkins Bloomberg School of Public Health, and Foundation Medicine, indicates that a gene commonly linked to colorectal cancer may also contribute to the development of other solid tumors. This large-scale analysis, encompassing over 350,000 patient biopsy samples, represents the most extensive investigation to date into the potential impact of a single mutated copy of the MUTYH gene on cancer risk. While inheriting two mutated copies of MUTYH has long been associated with a significant increase in colorectal cancer risk, the study sheds new light on the broader implications of this gene in cancer development. MUTYH encodes a vital enzyme involved in the base excision repair (BER) pathway, responsible for repairing DNA damage in human cells. Dysfunction in this pathway can lead to the accumulation of DNA mutations or cell death, potentially contributing to cancer development. Despite previous conflicting findings, this study underscores the importance of further research into the role of MUTYH mutations in cancer predisposition. In pursuit of answers, Paller collaborated with Foundation Medicine, a leading genomic profiling company, and a team of researchers, including Alexandra Maertens, Ph.D., from the Center for Alternatives to Animal Testing at the Bloomberg School of Public Health. Together, they employed an advanced algorithm to analyze genetic data from 354,366 solid tumor biopsies stored in the Foundation database. Among these samples, 5,991 exhibited one functional and one mutated version of the MUTYH gene, with 738 individuals losing their functional copy. Those with a single mutated copy displayed a distinct genetic signature indicating additional mutations and a defective BER pathway, leading to a modest increase in susceptibility to certain solid tumors like adrenal gland cancers and pancreatic islet cell tumors. However, they did not show an elevated risk of breast or prostate cancer, answering the original patient's query. These findings suggest that MUTYH variants may be implicated in a wider spectrum of cancers than previously recognized, prompting consideration of therapeutic implications. Paller underscores the need to explore whether targeting the BER pathway could reveal drug sensitivities, potentially offering a new therapeutic avenue against solid cancers for doctors to incorporate into their treatment strategies. Additional study co-authors hailed from Cardiff University School of Medicine in the United Kingdom and the University of Minnesota Masonic Cancer Center in Minneapolis. The research received support from various sources, including Department of Defense funding from the Congressionally Directed Medical Research Programs (grant W81XWH-22-2-0024), the National Institutes of Health (grant P30CA006973), and Advancing Cancer Treatment. Paller discloses her roles as a consultant or adviser for Dendreon, Omnitura, Exelixis, and AstraZeneca, along with receiving research funding from Lilly (Inst) and travel expenses from Bayer. Maertens declares ownership interests in Pfizer.