Colon cancers

Colon cancers 

Updated: 02/29/2024

© Jun Wang, MD, PhD

General features
  • Predominantly adenocarcinomas
  • #2 cause of cancer deaths in US after lung cancer
  • Most are sporadic cases, some have familial risk
Risk factors
  • Older age, obesity, physical inactivity, family history of colorectal neoplasia
  • Diet: High in red meat, animal fat, low fiber and overall low fruit/vegetable
  • Ulcerative colitis, Crohn’s disease, schistosomiasis
  • Polyposis syndrome and associated genetic abnormalities
Familial adenomatous polyposis and variants (APC or MUTYH gene)
Juvenile polyposis (SMAD4, BMPR1A)
Sessile serrated adenoma (KRAS, BRAF, etc)
Cowden syndrome (PTEN genes)
Peutz-Jeghers syndrome (STK11 gene)
Lynch syndrome and variants (MSH2, MLH1, PMS1, PMS2, MSH3 and MSH6 genes)
Pathogenesis
With MSI: commonly with activating mutation of BRAF
Without MSI: commonly activating KRAS mutation

Clinical presentations
  • May be asymptomatic
  • Right sided: Anemia, weakness and fatigue
  • Left sided: Changes in bowel habits (diarrhea or constipation) 
  • Elevated CEA
Radiologic finding
Key morphological features
Intramucosal carcinoma
  • Malignant change confined to mucosa
  • Invasive or in situ
  • Rarely metastasize to lymph nodes
  • Treatments: Polypectomy with clear margin, endoscopic mucosal resection
Genetic abnormalities
  • Microsatellite-instability mutations
  • CpG island hypermethylation
  • BRAF activation
  • KRAS
  • SMAD4

Treatment
  • Surgery, adjuvant therapy, neoadjuvant therapy
  • Worse prognosis if signet ring cells present


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