Colon cancer

Colon cancer
Blausen Medical Communications, Inc. · CC BY 3.0 · source
Name	Colon cancer
Field	Oncology, Gastroenterology, Pathology
Synonyms	Colorectal carcinoma (when including rectal disease)
Onset	Typically adults over 50, variable
Risks	Hereditary syndromes, inflammatory bowel disease, lifestyle factors
Diagnosis	Colonoscopy, biopsy, imaging, molecular testing
Treatment	Surgery, chemotherapy, radiation, targeted therapy, immunotherapy

Colon cancer Colon cancer is a malignant neoplasm arising from the large intestine epithelium, most often from adenomatous polyps. It is a leading cause of cancer morbidity and mortality worldwide, with management involving multidisciplinary teams across surgery, medical oncology, radiation oncology, and pathology.

Signs and symptoms

Patients commonly present with changes in bowel habits, visible hematochezia, iron-deficiency anemia, abdominal pain, and unexplained weight loss. Clinical presentations may also include bowel obstruction and perforation, with findings such as palpable abdominal mass and altered stool caliber prompting evaluation by specialists from Royal College of Surgeons, American College of Gastroenterology, European Society for Medical Oncology, National Comprehensive Cancer Network, and World Health Organization. Red flag symptoms lead to urgent referral pathways used by systems like the NHS and Centers for Disease Control and Prevention protocols.

Causes and risk factors

Major inherited risks include pathogenic variants in APC associated with familial adenomatous polyposis, germline mutations in MLH1, MSH2, MSH6, PMS2 and EPCAM causing Lynch syndrome, and mutations in MUTYH leading to MUTYH-associated polyposis. Acquired risks include chronic inflammation from Ulcerative colitis and Crohn's disease as treated in centers like Mayo Clinic and Cleveland Clinic, dietary patterns described by epidemiologists at Harvard T.H. Chan School of Public Health, smoking history documented by Surgeon General of the United States reports, and alcohol exposure studied by International Agency for Research on Cancer. Age, obesity, and diabetes are additional contributors emphasized in guidelines from American Cancer Society and population cohorts such as the Framingham Heart Study.

Pathophysiology

Carcinogenesis typically follows the adenoma-carcinoma sequence driven by successive genetic and epigenetic alterations in pathways regulated by APC, the Wnt signaling pathway, KRAS, TP53, and mismatch repair genes implicated in microsatellite instability observed in studies from Dana-Farber Cancer Institute and Johns Hopkins Hospital. Alternative serrated pathway lesions involve BRAF mutations described in literature from Memorial Sloan Kettering Cancer Center. Tumor microenvironment interactions with stromal cells, tumor-associated macrophages, and immune checkpoints such as PD-1/PD-L1 are central to progression and therapeutic response, with translational research contributions from National Institutes of Health and the European Molecular Biology Laboratory.

Diagnosis

Definitive diagnosis requires visualization and histologic confirmation via colonoscopic biopsy performed following protocols from American Society for Gastrointestinal Endoscopy and staging workup using computed tomography from vendors like GE Healthcare and Siemens Healthineers. Molecular testing for mismatch repair deficiency and RAS/BRAF mutation status, guided by College of American Pathologists recommendations and panels developed at MSKCC, informs prognosis and therapy selection. Ancillary tests such as fecal immunochemical testing promoted by World Gastroenterology Organisation and carcinoembryonic antigen measured in clinical laboratories at institutions like Johns Hopkins assist in surveillance.

Staging and prognosis

Staging uses the TNM framework promulgated by the American Joint Committee on Cancer and Union for International Cancer Control, integrating tumor invasion depth, nodal involvement, and distant metastases often detected in liver via magnetic resonance imaging or lung via chest CT. Prognostic estimates incorporate stage alongside biomarkers such as microsatellite instability status defined in studies from European Society for Medical Oncology and mutational profiles cataloged in databases like The Cancer Genome Atlas. Survival outcomes reported by registries including Surveillance, Epidemiology, and End Results Program and European Cancer Information System underpin guideline recommendations.

Treatment

Curative-intent management for localized disease centers on surgical resection performed by colorectal surgeons trained in programs at Royal College of Surgeons of England and American Board of Surgery, often followed by adjuvant chemotherapy regimens such as FOLFOX or CAPOX based on trials from cooperative groups like European Organisation for Research and Treatment of Cancer and North Central Cancer Treatment Group. Locally advanced rectosigmoid tumors may incorporate neoadjuvant chemoradiation coordinated with radiation oncology units at MD Anderson Cancer Center. Metastatic disease treatment includes systemic chemotherapy, targeted agents against EGFR or VEGF pathways developed by pharmaceutical consortia including Roche and Bristol Myers Squibb, and immunotherapy for mismatch repair–deficient tumors approved through regulatory agencies like Food and Drug Administration and European Medicines Agency. Local ablative therapies for liver metastases utilize interventional radiology platforms from Society of Interventional Radiology guidelines.

Prevention and screening

Screening reduces incidence and mortality through tests such as colonoscopy, flexible sigmoidoscopy, fecal immunochemical testing, and multitarget stool DNA assays endorsed by U.S. Preventive Services Task Force, American Cancer Society, and Canadian Task Force on Preventive Health Care. Population programs implemented by public health agencies including NHS England and Public Health England and research from Centers for Disease Control and Prevention have informed age-based screening initiation and intervals. Primary prevention strategies emphasize modulation of diet informed by World Cancer Research Fund reports, tobacco cessation promoted by World Health Organization, alcohol reduction policies supported by Global Alcohol Policy Alliance, weight management programs from National Institutes of Health, and surveillance of high-risk families via hereditary cancer clinics at centers like University of Texas MD Anderson Cancer Center.

Category:Gastrointestinal cancers