Colorectal Cancer
Sandra Van Schaeybroeck, Mark Lawler, Brian Johnston, Manuel Salto-Tellez, Jack Lee, Paula Loughlin, Richard Wilson and Patrick G. Johnston
Summary of Key Points
Epidemiology
• Colorectal cancer (CRC) is the second most common cancer in women and the third most common cancer in men worldwide.
• Within economically developed countries, the lifetime risk of developing CRC is 1 in 20.
• Because of increased screening rates, the incidence of CRC is declining for men and women in the United States.
• The incidence is 15 times higher in adults older than age 50 years, compared with those younger than age 50 years.
• Inherited genetic syndromes (hereditary nonpolyposis colorectal cancer [HNPCC] and familial adenomatous polyposis [FAP]: fewer than 10% of cases) and inflammatory bowel disease (IBD) in concert with dietary and environmental exposures increases risk for CRC.
• The 5-year overall survival rate has greatly improved in the last 2 decades, and is now approximately 65%, with variations across racial and ethnic subgroups.
Screening and Prevention of CRC
• High level of physical activity decreases the risk of CRC by up to 50%.
• Diets high in fiber and low in red, processed meat may alter risk of CRC.
• Calcium/vitamin D supplementation might have preventive effects.
• Aspirin and cyclooxygenase (COX)-2 inhibitors may prevent polyps and CRC, but are only recommended in high-risk patients.
• Premenopausal hormone replacement therapy reduces the incidence of CRC, but increases the risk of breast cancer and cardiovascular complications.
• There are mixed results in studies of the effects of statins on CRC risk.
• Colonoscopy is the mainstay of screening and a useful tool in the diagnosis of CRC. Sigmoidoscopy may reduce CRC incidence and mortality.
• Fecal occult blood is an acceptable screening tool.
• Virtual colonoscopy, the detection of abnormal DNA within stool sample and capsule endoscopy are potentially new screening tests.
• Screening is based on risk categories that take into account age; race; personal history of IBD, polyps, or cancer; family history of CRC; and presence of hereditary syndromes.
Diagnosis and Staging
• CRC is often insidious in development, underscoring the importance of screening.
• Altered bowel habits, blood per anum, fatigue, anemia, and weight loss are frequent symptoms.
• Obstruction is the most common acute surgical problem (approximately 30% of left-sided lesions present with an obstruction).
• Approximately 5% of CRC patients will be diagnosed with synchronous cancer. The liver is the most common site for synchronous metastasis.
• Approximately 20% to 40% will have synchronous polyps with cancer primary.
• Computed tomography (CT) scan, magnetic resonance imaging (MRI), and positron emission tomography (PET) are imaging tools used in the staging of CRC.
• Intraoperative ultrasound is the most sensitive method to evaluate liver for metastases.
• Tumor size is not as critical as depth of invasion and nodal status in determining prognosis.
• High histologic grade, lymphatic invasion, venous invasion, and involvement of surgical resection margins are independent adverse prognostic factors.
Molecular Pathogenesis
• The “Vogelgram” highlights the involvement of specific oncogenes and tumor suppressor genes in the colorectal adenoma to carcinoma transition, and involves APC, KRAS, TP53, and DCC.
• The APC tumor suppressor gene is defective in more than 80% of colon adenomatous polyps and cancers. KRAS, TP53, and BRAF are mutated in 40% to 50%, approximately 50%, and 8% of CRC, respectively.
• Deletions of 18q21 (location for DCC, SMAD2 and SMAD 4) also play a role in CRC carcinogenesis.
