Introduction:
Hereditary nonpolyposis colorectal cancer is an acquired condition that causes colon and rectum malignancies. People with this condition are at high risk of developing uterus, ovary, stomach, and liver cancer. It causes symptoms like blood in stools, constipation, a decrease in the size of the stool, and abdominal cramps. First, tests like genetic testing and colonoscopy diagnose it. Then, it is treated by removing the polyps through endoscopic therapy or surgical removal.
What Is Hereditary Nonpolyposis Colorectal Cancer?
Hereditary nonpolyposis colorectal cancer occurs in people who have inherited the gene, increasing the risk of getting cancers in many parts of the body but the colon and rectal. This condition is transferred from the parents to their offspring.
Nonpolyposis refers to the occurrence of colon cancer only when small counts of polyps are present or no polyps are present. This condition is also called Lynch syndrome.
This condition also causes cancer in other body parts like the small intestine, liver, stomach, pancreas, gallbladder, ovary, uterus, and endometrium.
What Causes Hereditary Nonpolyposis Colorectal Cancer?
Mutations in the gene that repairs our DNA (deoxyribonucleic acid) cause hereditary nonpolyposis colorectal cancer. The genes MLH1 (mutL homolog), MSH2 (mutS homolog 2), MSH6 (mutS homolog 6), PMS2 (postmeiotic segregation increased 2), and EPCAM (epithelial cellular adhesion molecule). These genes repair the errors when the DNA is replicated for cell division.
EPCAM gene variations are not directly involved in DNA variation repair. However, since it lies close to the MSH2 gene, it inactivates the MSH2 gene and leads to the build-up of DNA errors leading to cancer.
These genes are called mismatch repair genes, as they work together to repair the errors during DNA replication. Variations in any one of the genes fail to fix the DNA errors, and there is an increase in abnormal cell division. This leads to cancer formation. For example, the variations in MLH1 and MSH2 genes cause a 70 % to 80 % increased risk of cancer in a person. Conversely, MSH6 and PMS2 have relatively low chances of developing cancer, about 25 % to 60 %.
What Are the Symptoms of Hereditary Nonpolyposis Colorectal Cancer?
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Blood in stool.
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Abdominal cramps.
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Persistent constipation.
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Reduced stool size, which is persistent for an extended period.
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Diarrhea irrespective of dietary changes or an illness.
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Abdominal bloating.
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Gas pain.
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Abdominal fullness with or without cramps.
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Unexplained weight loss.
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Vomiting.
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Lack of energy and feeling tired.
What Tests Are Used to Find Hereditary Nonpolyposis Colorectal Cancer?
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Family History: The physician must gather a complete family history before deciding on other diagnostic procedures. A few criteria are mentioned below that need to be fulfilled to conclude the diagnosis of this condition.
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Amsterdam I:
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Three relatives should be detected with colorectal cancer.
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One colorectal cancer case should be detected in a relative at 50 years or below.
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One relative with colorectal cancer should be a first-degree relation like a sibling, parent, or child to the other two people with colorectal cancer.
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Colorectal cancer happens in two successive generations.
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Amsterdam II:
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Two hereditary nonpolyposis colorectal cancer-associated cancers like uterine cancer, renal pelvis cancer, small intestine cancer, and endometrial cancer.
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One relative with hereditary colorectal cancer is the first degree to the other two persons with cancer.
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One relative with colorectal cancer should be diagnosed before the age of 50.
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Hereditary nonpolyposis colorectal cancer runs in two successive generations.
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Hereditary Nonpolyposis Colorectal Cancer Like:
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It involves families who have individuals with two colorectal cancer and one uterine cancer or two relatives with advanced precancerous polyps and colorectal cancer.
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One case of uterine or colorectal cancer in the close circle should be diagnosed before 50 years.
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One relative with hereditary colorectal cancer is a first-degree relative to the other two with colorectal cancer or polyps.
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Hereditary colorectal cancer occurs in two successive generations.
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If these criteria are met, the diagnostic tests should be performed quickly.
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Genetic Testing: Genetic testing is done by obtaining a blood sample from the patient with a family history of hereditary nonpolyposis colorectal cancer. The test reveals if there is a mutation present or not. If there is a gene mutation, further investigations like colonoscopy can be performed for a final diagnosis.
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Colonoscopy: A long flexible tube-like structure with a camera and a light is inserted into the anus to view the colon and the rectum through a monitor outside. It is the best approach to view if polyps or cancer is present in the colon and rectum. The patient undergoing this procedure will be given anesthesia (a sleep medication) so that the patient may not feel pain or discomfort.
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Microsatellite Instability Testing: This test is considered to check if the tumor occurrence is due to defective mismatch repair genes.
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Biopsy: A small tissue of the colon polyp is removed with the help of a colonoscopy and is viewed under a microscope to detect any pathological changes. This is a confirmatory test that reveals the presence of a malignancy.
How to Treat Hereditary Nonpolyposis Colorectal Cancer?
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Colonoscopy: If the polyp size is small, it will be removed while performing the colonoscopy.
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Surgery: Surgical removal will be considered if the polyp size is relatively big and cannot be removed.
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Total Proctocolectomy With Brooke Ileostomy: The colon and the rectum are completely removed in this procedure. The ileum, the last part of the small intestine, is made as an artificial opening. This procedure is considered when the cancer is invasive, and there is improper functioning of the anal sphincter or in elderly patients where the anal sphincter function is reduced.
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Colectomy With Ileorectostomy: The colon is removed, leaving the whole rectum or a part of the rectum. The small intestine is attached to the upper part of the rectum. This procedure is done in patients who have few polyps in the rectum or no polyps in the rectum. However, continuous monitoring is required to look for polyps in the rectum.
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Restorative Proctocolectomy: The colon and the rectum are entirely removed. The final part of the small intestine ileum is attached to the most distal portion of the rectal mucosa, and an ileal pouch is created. This pouch collects the digestive waste products and stores them for the time being until elimination from the body.
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What Is the Prevalence of Hereditary Nonpolyposis Colorectal Cancer?
Hereditary nonpolyposis colorectal cancer is prevalent in people of both genders. However, females are at high risk of developing cancer in the reproductive systems, like uterine cancer, ovarian cancer, and endometrial cancer.
What Is the Effect of Surgery on Patients With Hereditary Nonpolyposis Colorectal Cancer?
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Surgery does not affect the lifestyle of the patient.
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Sexual life is also not affected.
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Females planning for pregnancy can consult a physician and plan for pregnancy after a year, as the abdominal scar needs time to heal.
What Is the Prognosis of Hereditary Nonpolyposis Colorectal Cancer?
The five-year survival rate of patients with hereditary nonpolyposis colorectal cancer is around 60%.
Conclusion
Hereditary nonpolyposis colorectal cancer is an acquired condition resulting from impairment in the gene that repairs DNA replication. When there is an error in the matchmaking repair genes responsible for fixing the error caused by DNA replication, an accumulation of multiplied error DNA leads to cancer. It causes symptoms like stomach pain, cramps, blood in stools, reduced size of stools, vomiting, and unexplained weight loss. It is found by performing tests like colonoscopy, genetic testing, and microsatellite instability testing. It is best treated with surgical removal of the colon and rectum entirely if the tumor is invasive and the terminal part of the small intestine is attached to create an artificial opening to excrete the feces outside the body. In addition, there are a few variations in the surgical techniques depending on the nature and location of the tumor. Though this condition can be life-threatening if not detected and treated early, invasive surgical procedures can resolve the situation. However, early genetic testing detection can prevent the disease's severity and be monitored with frequent colorectal screenings.
