Gastroenterology

As cancer death rates drop overall; doctors have noted a frightening anomaly: deaths from colorectal cancer in people under 55 appear to be creeping up. According to the American Cancer Society, deaths in this younger group increased by 1 percent between 2007 and 2016. A new study led by Salk Institute scientists suggests that high-fat diets fuel colorectal cancer growth by upsetting the balance of bile acids in the intestine and triggering a hormonal signal that lets potentially cancerous cells thrive.

Tumor progression

The findings, which appeared in Cell on February 21, 2019, could explain why colorectal cancer, which can take decades to develop; is being seen in younger people growing up at a time when higher-fat diets are common. “This study provides a new way to lower inflammation, restore intestinal health and to dramatically reduced tumor progression,” says Professor Ronald Evans, director of the Gene Expression Laboratory, Howard Hughes Medical Institute investigator and holder of Salk’s March of Dimes Chair in Molecular and Developmental Biology.

The research, conducted in a mouse model, suggests how lifestyle and genetics converge. The researchers found that animals with an APC mutation, the most common genetic mutation found in humans with colorectal cancer; developed cancer faster when fed a high-fat diet.

Gene Expression

“It could be that when you’re genetically prone to get colon cancer; something like a high-fat diet is the second hit;” says study co-author Ruth Yu, a staff researcher in the Gene Expression Laboratory at Salk.

The intestine and colon (commonly lump together as the “gut”) are hard-working organs. As you eat, your gut needs to constantly regenerate its lining to undo the damage done by digestive acids. To do this, the gut houses a population of stem cells that can replenish lining cells when needed.

Hormonal signals

Scientists have found that colorectal cancers often originate from mutations in these stem cells. The most common colorectal cancer-linked mutation is in a gene called APC, which normally acts as a “tumor suppressor” gene because it controls how often cells divide. Mutations in the APC gene can remove that control and allow cells to divide rapidly and become cancerous.
Over the last four decades, Evans and his colleagues have investigated the roles of bile acids. (30 types of bile acids float around in the gut to help digest food and absorb cholesterol, fats and fat-soluble nutrients.) Among the lab’s discoveries was the revelation that bile acids send hormonal signals to intestinal stem cells through a protein called the Farnesoid X receptor (FXR). because For the new study, the researchers uncovered how high-fat diets affect that hormonal signaling.