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Updated: March 25, 2024 11:55 p.m. IST
Washington [US]March 25 (ANI): A gene linked to colorectal cancer appears to play a role in the development of other solid tumors, according to a study.
A study of more than 350,000 patient biopsy samples by researchers at the Johns Hopkins Kimmel Cancer Center, the Johns Hopkins Bloomberg School of Public Health, and the Medicine Foundation.
Scientists have known since the early 2000s that inheriting two mutant copies of the MUTYH gene increases the risk of colorectal cancer 93-fold and is a leading cause of the disease in people under 55 years of age. The current study, published online February 23 in JCO Precision Oncology, is the largest to date examining whether a single mutant copy of MUTYH influences cancer risk.
“We know that two missing copies of MUTYH greatly increase the risk of colon cancer, and it now appears that missing just one copy may slightly increase the risk of other types of cancer,” says the study’s lead author, Channing Paller, MD. . director of prostate cancer clinical research and associate professor of oncology at the Johns Hopkins University School of Medicine. He co-led the work with Emmanuel Antonarakis, MD, associate director of translational research at the Masonic Cancer Center and Clark Professor of Medicine at the University of Minnesota School of Medicine. He was at Johns Hopkins at the time the research was conducted.
The MUTYH gene encodes a critical enzyme in the base excision repair (BER) pathway, which repairs DNA damage in human cells. When the BER pathway is not working, routine DNA damage is not repaired, leading to additional DNA mutations or cell death.
Since 2021, Paller co-leads PROMISE, a genetic registry of patients with inherited mutations in prostate cancer. When one of her patients asked whether her MUTYH mutation, of which she had one defective copy instead of two, affected his aggressive prostate cancer, there was not enough data on MUTYH variants to answer the question, Paller says. Previous studies reached conflicting results on whether a single heterozygous MUTYH mutation could predispose a person to cancer.
Looking for an answer, Paller reached out to Foundation Medicine, a Massachusetts-based genomic profiling company that maintains one of the largest cancer genomic databases in the world. With researchers from Foundation Medicine; Alexandra Maertens, Ph.D., of the Center for Alternatives to Animal Testing at the Bloomberg School of Public Health; and others, the team applied an advanced algorithm to analyze genetic data from 354,366 solid tumor biopsies stored in the Foundation’s database.
Within that population of tumor samples, 5,991 had a functional version and a mutated version of MUTYH. Of them, 738 (about 12%) had lost their functional copy of the gene, leaving them with only the mutated copy. Those with a single mutated copy of MUTYH showed a genetic signature, like a fingerprint, of additional genetic mutations and a defective BER pathway. Individuals with that genetic signature had a modest increase in susceptibility to a subset of solid tumors, including adrenal gland cancers and pancreatic islet cell tumors. However, they did not have an increased risk of breast or prostate cancer, which resolved the original patient’s question.
The results suggested that MUTYH variants could be involved in a broader range of cancers than previously known, Paller said.
“The next question is whether this finding has therapeutic implications,” he said. “Can we target the BER pathway for potential drug sensitivities?” If so, doctors could add a new therapeutic approach to their arsenal of tools against solid cancers. (ME TOO)
