Colorectal cancer

Colorectal cancer begins in the mucosal lining of the large intestine and is most often an adenocarcinoma arising from glandular epithelium.¹ The colon absorbs water and forms stool, while the rectum stores stool before elimination; tumors in these sites can therefore produce overlapping but sometimes distinct symptoms.

Many tumors evolve from precancerous polyps through accumulated alterations in pathways involving genes such as APC, KRAS, and TP53. The conventional adenoma-carcinoma sequence is not the only route: serrated lesions can follow a molecular pathway associated with abnormal DNA methylation and may be harder to recognize endoscopically. Cancer cells can invade the bowel wall, nearby lymph nodes, and distant organs, especially the liver and lungs.²

Age, inherited susceptibility, chronic intestinal inflammation, and several lifestyle-related exposures shape colorectal cancer risk.³ Risk is increased by a personal or family history of colorectal cancer or advanced polyps, familial adenomatous polyposis, Lynch syndrome, inflammatory bowel disease, smoking, alcohol consumption, obesity, and diets associated with low fiber and high processed-meat intake.

Early disease may cause no symptoms. Possible warning signs include blood in stool, iron-deficiency anemia, persistent changes in bowel habits, abdominal pain, and unexplained weight loss; these findings can also have noncancerous causes. Screening is intended for people without symptoms and can detect both cancer and removable precursors. Available approaches include colonoscopy, stool-based tests, and flexible sigmoidoscopy; recommended starting ages and intervals depend on national guidance and individual risk.^{3 4}

A diagnosis requires examination of tissue obtained during colonoscopy or another biopsy procedure.¹ Pathologists establish tumor type and grade, while staging evaluates invasion through the bowel wall, regional lymph nodes, and distant metastases. Testing for mismatch-repair deficiency or microsatellite instability is clinically useful because it can identify Lynch syndrome and predict benefit from some immune-based treatments.

Localized disease is generally treated with surgical removal of the tumor and regional lymph nodes; chemotherapy is added in selected stages or when recurrence risk is substantial. Rectal cancer may require combinations of radiation, chemotherapy, and surgery. Advanced disease can be treated with systemic chemotherapy, targeted drugs directed at selected molecular alterations, and immunotherapy for some mismatch-repair-deficient tumors.^{5 6} Care is increasingly guided by molecular profiling rather than anatomy alone.

Colorectal cancer is biologically diverse, and its less common forms and pathways affect prevention and treatment.

• Inherited disease: Lynch syndrome is the most common inherited colorectal cancer syndrome, while familial adenomatous polyposis can produce hundreds to thousands of adenomatous polyps and a very high lifetime risk without preventive management.²
• Inflammatory disease: Long-standing ulcerative colitis or Crohn disease involving the colon raises risk, but surveillance timing depends on disease duration, extent, inflammation, and other factors.
• Young-onset disease: Diagnosis before age 50 has increased in several high-income countries even while screening has reduced incidence in older adults; symptoms in younger people should not be dismissed solely because of age.
• Unusual spread: Some rectal tumors spread through pelvic structures, whereas colon cancers commonly metastasize first to the liver through portal blood flow. This anatomy helps determine imaging, surgery, and systemic treatment.

Adenoma

A gland-forming polyp that can become malignant but is not itself cancer.

Colonoscopy

Endoscopic examination of the entire colon and rectum, allowing biopsy or polyp removal.

Microsatellite instability

A molecular pattern caused by defective DNA mismatch repair and associated with some colorectal cancers.

Staging

Assessment of how far a cancer has spread, including the bowel wall, lymph nodes, and distant organs.