What is hereditary colorectal cancer? About 75% of colorectal cancer patients have no corresponding family history of cancer and they are older (over 65 years old). This type of colorectal cancer is mostly determined by environmental factors and is called disseminated colorectal cancer. The remaining 25% of colorectal cancer patients mostly have corresponding family history, and there are even 5-10% of patients whose bowel cancer occurrence is related to heredity, and this type of colorectal cancer is called hereditary colorectal cancer. Ding Peirong, Department of Colorectal Medicine, Cancer Hospital of Sun Yat-sen University Hereditary colorectal cancer mainly includes: familial adenomatous polyposis (FAP) (1%), Lynch syndrome (Lynch syndrome) (3-5%), and some other types. FAP: polyps tend to appear around the age of 15 years Familial adenomatous polyposis is an autosomal dominant disorder characterized by a germline mutation in the APC gene located at the 5q21 locus. The main pathological change is the widespread appearance of tens to hundreds of polyps of various sizes in the large intestine, and in severe cases, the polyps can occur from the oral cavity to the rectum and anal canal, with the number of polyps reaching several thousand. Patients are not born with colon or rectal polyps. Most of the polyps appear around the age of 15, and the number of polyps is small at the beginning and increases with age. Familial adenomatous polyposis develops at an earlier age than common colorectal cancer. If left untreated, almost every case will develop colorectal cancer, and many patients will develop gastric and duodenal polyps, sclerofibromas, thyroid and brain tumors, osteomas, congenital retinal pigment epithelial hypertrophy, multiple dentition, and dermatomal cysts. Why should I be concerned about hereditary colorectal cancer? For patients themselves, patients with hereditary bowel cancer have a significantly increased risk of developing multiple primary colorectal cancers (bowel cancers in other locations) and multiple primary extraintestinal cancers (such as endometrial cancer, genitourinary tumors, and small bowel cancer). Determining whether a patient has hereditary bowel cancer can improve prognosis by guiding treatment and follow-up, and by early detection and management of recurrent bowel cancer or other related tumors. For the family members (first, second and third degree relatives) of patients with hereditary bowel cancer, the risk of developing bowel cancer and hereditary bowel cancer-related tumors is significantly higher than that of the general population, and the onset of the disease is younger. Case 1: A 74-year-old male patient was operated for a small intestinal mass 5 years ago; one year after the operation, he went to the hospital again for review because of abdominal pain and was found to have sigmoid colon cancer; during the operation again, he was found to have a mass in the transverse colon in addition to the sigmoid colon, and both were confirmed to be colon cancer after resection; one year after the second operation, the patient had abdominal pain again and was reviewed again and was found to have ascending colon cancer; the third operation was performed and resected; less than two years after the operation, the patient was found to have a cancer in the ascending colon. Less than two years after the operation, the patient was admitted to the hospital again because of abdominal pain and was found to have descending colon cancer, and finally the whole colon was removed. The patient later came to our hospital for screening of Lynch syndrome and was diagnosed with Lynch syndrome. The patient in this case is a typical patient with hereditary colorectal cancer (Lynch syndrome). If the patient had recognized this when the tumor was first discovered and had been closely followed up after surgery or had the whole colon removed prophylactically, it would have been possible to avoid the recurrence of bowel cancer. Case 2 A 26-year-old male patient came to the hospital with abdominal pain, and colonoscopy revealed ascending colon cancer, and CT examination revealed multiple implantation metastases in the abdominopelvic cavity; family history was followed up to find that his mother had colon cancer 7 years ago, which was cured by surgery outside the hospital. The patient was screened for Lynch syndrome and finally diagnosed with Lynch syndrome. However, because of the extensive metastases in the abdominal cavity, the patient was deprived of surgery and had to undergo palliative chemotherapy. This is a very regrettable event, which could have been avoided if her mother’s doctor had been aware of this hereditary bowel cancer at the time of consultation and recommended regular screening for her family. Case 3 Female 55-year-old patient with colon cancer found on physical examination. When we followed up the patient’s medical history, she had endometrial cancer 6 years ago; there was an obvious family history of endometrial cancer in her daughter and colon cancer in her nephew. We considered the patient highly suspicious as a patient with Lynch syndrome, which was confirmed by post-surgical genetic testing. The family was screened for high-risk cancers, and the youngest daughter was found to have colonic villous adenoma (precancerous lesion), given a colonoscopic polyp removal, and advised to repeat colonoscopy and other related tests in 1-2 years. This case is also a typical hereditary colorectal cancer because of timely diagnosis, timely detection and treatment of the precancerous lesion in her relative, and a different review plan for her than other patients with sporadic bowel cancer. Doubt: No one in the family has bowel cancer or other tumors, so why might she have hereditary bowel cancer herself? In a family, not every individual may have hereditary colon cancer, and not every generation will have someone with the disease. Moreover, there is always the first person in each family who has the disease (or the first person who is detected), and this person is clinically known as a presentee. In the absence of a history of bowel cancer or other related tumors in the family of the first-comer, the mutation in the first-comer may have occurred from the embryonic period and will be passed on to his offspring. As mentioned earlier, Lynch syndrome is caused by mutations in one or more of the MMR genes (MLH1, MSH2, MSH6, PMS2), and mutations in genes can be divided into genetic mutations (also known as germline mutations or germline mutations) and acquired mutations (also known as somatic mutations). The main difference between them is that the former is a mutation inherited from the parents, while the latter is a mutation that occurs later in the DNA of individual cells. If a somatic mutation (e.g., hypermethylation of a gene) causes bowel cancer, then the risk of the family having bowel cancer or other tumors is the same as in the general population.