Cancer is rarely detected in the right-sided colon because genes’ function of ejecting tumour cells and other foreign substances there is as strong as in the small intestine, which has a powerful immune system, a Japanese research team recently announced.
It is known that colorectal cancer occurs in the left-sided colorectum at an incident rate of some 80% while the small intestine and the right colon are almost cancer-free, reports The Japan Times.
Through endoscopic intestinal step biopsies and exhaustive genetic analysis, the group of researchers from the National Cancer Centre and Osaka University found that the expression of genes related to xenobiotic stimulus and antimicrobial peptide is high in the right colon.
The finding suggests that foreign substances not digested or absorbed in the small intestine undergo metabolism in the right colon, said Yutaka Saito, endoscopy division head at the National Cancer Centre Hospital, and colleagues.
In their study, which covered both colorectal cancer patients and healthy people, the researchers also confirmed differences in gene expression in the normal mucosa in patients compared with healthy controls. In particular, those having tumours showed a considerable variation in gene expression in non-tumour tissues, even in the terminal ileum distant from the tumour site.
The results imply cancer-predisposing conditions in seemingly normal tissues, they said.
Furthermore, the study revealed abnormality in gene expression in the terminal ileum, where T cells, which play a centre role in the immune response system, are activated, of patients with advanced colorectal cancer.
The researchers think that control of the terminal ileum may lead to the prevention of the cancer.
Pointing out that colorectal cancer is the most common type of cancer among Japanese people, Shinichi Yachida, professor at the university and the corresponding author, said: “Pre-emptive medicine that can bring presymptomatic people back into good health is necessary.”
He also expressed hope that a novel colorectal cancer treatment focusing on the small intestine’s immune system will be developed.
The research findings were published in the online version of Molecular Cancer.
Study details
Variability in non-tumour areas of colorectal cancer patients as revealed by endoscopic intestinal step biopsies
Shoko Ikuta, Yutaka Saito, So Takata et al.
Published in Molecular Cancer on 7 November 2024
Abstract
A comprehensive endoscopic small and large intestinal untargeted step biopsy procedure was conducted to compare gene expression between the normal intestinal mucosa of healthy individuals and that of patients with colorectal tumours. From 78 participants (healthy individuals [n = 17], patients with colorectal conventional adenomas [n = 6], patients with Tis–T1 colorectal cancer [n = 41], patients with T2–4 colorectal cancer [n = 14]), biopsies of normal mucosa of the terminal ileum, right-sided colon (cecum and ascending colon), and left-sided colorectum (descending colon, sigmoid colon, and rectum) were obtained using a lower gastrointestinal endoscope. RNA was extracted from all samples, and total transcriptome sequencing was performed. Transcriptome data from 388 samples was analyzed. DNA was also extracted from tumour biopsy tissues and analysed for whole-exome sequencing. In healthy individuals, gene expression differed significantly among the terminal ileum, right-sided colon, and left-sided colorectum, presumably linked to embryological factors. There were differences in gene expression in the normal mucosa in colorectal cancer patients, compared to healthy controls. Patients with tumours, especially T2–4 colorectal cancer, showed considerable variation in gene expression in non-tumour tissues, even in the terminal ileum distant from the tumour site. Based on endoscopic biopsies, the results imply cancer-predisposing conditions in seemingly normal tissues. The present study points to the importance of small intestine and cancer-predisposing conditions in the colon of colorectal cancer patients, with possible implications for developing novel immunotherapy and other therapeutic modalities.
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