![The Gut Microbiome and Colon Cancer Development]()
Risk factors for colorectal cancer—including genetic predisposition, genotoxic factors, and prolonged exposure to chronic inflammation—are known to be influenced by microbes in the gut.
In a study published online on June 7 in Cellular and Molecular Gastroenterology and Hepatology, Winfried Edelmann, Ph.D., Elena Tosti, Ph.D., and colleagues showed that onset of inflammation-associated colon cancers is associated with defects in DNA mismatch repair. Such defects trigger a 50- to 1,000-fold increase in mutation rates and cause Lynch Syndrome, the most common inherited form of colon cancer. Focusing on intestinal epithelial cells in a mouse model, the researchers found that the loss of both mismatch repair and TGFBR2 tumor suppressor genes leads to colorectal cancers with molecular features closely resembling human inflammation-associated colon tumors. Colon-cancer development in the mice was found to be strongly controlled by the composition of the gut microbiome, which in turn was influenced by the TGFBR2 status of the tumors. This study provides new insights into the development of inflammation-associated colon cancers with DNA mismatch repair deficiency.
Dr. Edelmann is professor of cell biology and of genetics and is the Joseph and Gertrud Buchler Chair in Transgenic Medicine at Einstein. Dr. Tosti is an associate of cell biology at Einstein.
Posted on: Thursday, June 30, 2022