A high-fat diet rich in animal fats such as meat switches on a regeneration signal in colon cancer cells known as YAP1, encouraging the disease to spread to the liver, according to a new study. In South Korea, the number of colorectal cancer patients under 50 has risen 65.7% over five years, prompting the government to revise its screening system.
An MIT research team has identified the cellular pathway through which a high-fat diet promotes the spread of colorectal cancer to the liver, according to a paper recently published in the journal Science, medical sources said on the 1st. MIT professor Omer Yilmaz, Harvard Medical School professor Nilay Sethi and Alpaslan Tasdogan, a professor at University Hospital Essen in Germany, served as co-corresponding authors, while MIT postdoctoral researcher Swagata Goswami was among the first authors.
Most colorectal cancer deaths result from metastasis beyond the colon, and the liver is the most common site. According to the research team, up to one-third of patients in the United States diagnosed at stage 2 or 3, before metastasis, relapse with metastatic disease after surgery.
In mouse experiments, a high-fat diet activated an enzyme that produces ceramide, a fat molecule, and ceramide helped YAP1 move into the cell nucleus. YAP1 is a protein used to repair damaged intestinal tissue, and cancer cells appropriate that repair function to escape the primary site, the researchers said. When the ceramide-producing gene or YAP1 was suppressed, liver metastasis fell sharply.
The association also appeared in human data. An analysis of gene expression data from colorectal cancer patients found that the higher a patient's body mass index, the higher the expression of YAP1-related genes, and patients with high expression of those genes had lower survival rates.
The team said there are no dietary recommendations yet that can be applied directly to patients after diagnosis. It also cited drug selectivity as a limitation, because ceramide is needed in normal tissue as well. The researchers plan to develop drugs that inhibit the DEGS1 and DEGS2 enzymes.
In South Korea, the increase among younger people is pronounced. According to cancer registration statistics on the Korean Statistical Information Service, the number of colorectal cancer patients under 50 rose from 3,130 in 2018 to 5,187 in 2023. Among those in their 20s and 30s, the figure climbed from 864 to 1,948, an increase of more than 125%.
Park Go-woon, a professor of colorectal surgery at Soonchunhyang University Bucheon Hospital, said the trend reflects a combination of eating habits, drinking, smoking, lack of exercise, obesity and genetic factors. Research seeking the causes of early-onset colorectal cancer in gut microbes was also presented at an American Society of Clinical Oncology event in Singapore in June this year, but a causal link has not yet been established. Even so, the overall incidence rate of colorectal cancer, adjusted for population structure, shows no clear upward or downward trend, according to e-Narajipyo, the government's national statistics indicator portal.
As of 2023, there were 340,064 people living with colorectal cancer, or 12.4%, ranking fourth after thyroid, stomach and breast cancer. Screening participation is low. The colorectal cancer screening rate in 2024 was 40.3%, below that for liver cancer at 74.6%, breast cancer at 63.5% and stomach cancer at 63.2%. The government is pushing a plan to introduce colonoscopy as the primary test in the national screening program from 2028 and to widen the eligible age range to 45 to 74.
The findings come with the caveat that they are based on animal experiments. Other animal studies have reported that a short period on a high-fat diet in the early stages of the disease suppressed peritoneal metastasis. Results on the relationship between diet and metastasis vary with experimental conditions, so interpretation requires caution.
