Colorectal cancer is one of the most common digestive tract malignant tumors. The public generally thinks it is a disease of the elderly. However, in recent years, colorectal cancer has shown a significant trend of younger people.

Recently, a new study by Ma Yanlei, a professor at Fudan University Affiliated Cancer Hospital, revealed for the first time that young people with bowel cancer younger than 50 years old (early-onset bowel cancer) and elderly people with bowel cancer older than 50 years old (delayed bowel cancer). ), there are significant differences in gut flora, metabolic profiles, bacterial enzyme gene profiles, etc., and a diagnostic model is developed based on the "bacteria-metabolite-bacterial enzyme gene combination" markers. Early screening and accurate detection of young people at high risk of bowel cancer and patients will further promote the transformation and application of microbiota-based diagnostic strategies in the first-line clinical practice. The results were recently published online in Gut.

Don't miss the "window period" of early diagnosis

In recent years, bowel cancer has shown a significant trend of younger age. According to estimates by the American Cancer Center, if this trend continues, the incidence of bowel cancer among young people will double in the next 15 years, and 20% of bowel cancers will occur in people under the age of 50.

In 2013, for the first time in Shanghai, community colorectal cancer screening was included in public health services, but mainly for the elderly. Colorectal cancer in young people is usually detected after symptoms (change in bowel habits, blood in the stool, diarrhea, alternating diarrhea and constipation, local abdominal pain, etc.) .

"Although colonoscopy is a 'sharp tool' for detecting colon cancer, the benefits of widespread use of colonoscopy for early screening among young people may not outweigh the risks, and overdiagnosis may cause unnecessary economic burdens." Ma Yanlei told the China Science Journal , "Among the colorectal cancer patients in China, young people aged 20 to 34 accounted for 1% of the total number of patients; people aged 35 to 49 accounted for 6.8% of the total number of patients."

Exploring the development of better risk prediction tools to assist in the early identification of such high-risk young colorectal cancer patients and establishing better screening strategies has become the focus of current research on the clinical diagnosis of young colorectal cancer.

Mapping the microbiota and metabolite profiles of intestinal cancer in youth

The gut microbiota is an important microenvironment related to the health of the human gut. At present, many studies have confirmed that intestinal microecological disturbance is a key environmental factor in the occurrence and development of colorectal cancer, and the intestinal microbiota of the elderly population is significantly different from that of the young population.

Are there pathogenic bacteria profiles and metabolite profiles with diagnostic value in young patients with bowel cancer? Are these microbiota and metabolites important factors in the induction of intestinal cancer in youth?

In response to these problems, Ma Yanlei's team took 4 years to compare a total of 549 Chinese young and elderly patients with colorectal cancer with age-matched healthy people, conducted fecal metagenomic and metabolomics sequencing analysis, and constructed a model based on multi-omics characteristics. A random forest model was used to identify bowel cancer in young adults.

Using a large-sample cohort, the researchers mapped the gut microbiota and metabolite profiles of young Chinese colon cancer patients for the first time in the world. The results showed that the intestinal flora of young colorectal cancer patients was severely imbalanced, and the fecal microbial diversity was significantly decreased. In terms of the composition of the flora and metabolic profiles, the young colorectal cancer was also significantly different from the elderly colorectal cancer.

The study also found that the multi-omic features of colorectal cancer in youth were mainly characterized by pathogenic bacteria enrichment, red meat diet-related bacteria enrichment, and increased metabolism of tryptophan, bile acid, and choline; Activation of reaction pathways composed of alkali metabolites and bacterial choline metabolizing enzymes may be potential intervention targets for the development of intestinal cancer in young adults. Older colorectal cancer is characterized by enrichment of Fusobacterium nucleatum, excessive consumption of short-chain fatty acids, and a shift in acetate/acetaldehyde metabolism to acetyl-CoA metabolism.

Provide strategies and directions for early screening and diagnosis

To evaluate the multi-omics label classification ability of young colorectal cancer, the researchers constructed a random forest classifier model, and confirmed that the prediction model based on the combined markers of metagenomic, metabolome and bacterial enzyme genes has the ability to distinguish young colorectal cancer patients from healthy people. It has strong potential and can be used for early screening of bowel cancer in young people in the future.

"Based on the study of young people's intestinal cancer, intestinal flora spectrum and multi-omics characteristics, some health tips can be put forward for the prevention of intestinal cancer in young people." Ma Yanlei added, "First of all, we should avoid high-risk factors, quit smoking, and eat as little fried food as possible. , high cholesterol, high fat foods. In addition, we must change bad eating habits, increase the intake of dietary fiber and vitamins, appropriately increase physical exercise and maintain a happy mood.”

The study believes that it is very important for young people to improve their awareness and ability to prevent bowel cancer. On the one hand, they should develop healthy eating habits in their daily lives; on the other hand, if they usually have abdominal discomfort or change in bowel habits and stool shape , should go to the hospital in time, and actively carry out colorectal cancer screening.

"Early detection of colorectal cancer or precancerous lesions has a significant effect on improving the quality of life of colorectal cancer patients and improving the therapeutic effect." Ma Yanlei said, "This work aims to understand the pathogenesis of colorectal cancer in young people and explore the early screening of colorectal cancer suitable for young people. , early diagnosis methods provide a new perspective and direction."

Related paper information: http://dx.doi.org/10.1136/gutjnl-2022-327156

(Original title "In recent years, bowel cancer has shown a significant trend of younger age, "a "weapon" for early screening of youth bowel cancer")