In the United States, 102,480 new cases of colon cancer were expected in 2013 (men 50,090; women 52,390) (1), and 40,340 new cases of rectal cancer were expected in 2013 (men 23,590; women 16,750). Colorectal cancer is the second leading cause of cancer-related death in the United States with 50,830 deaths annually. Age is a major risk factor in developing colon cancer. The lifetime risk of developing colorectal cancer is approximately 5% with the vast majority of cancers occurring after age 50 years. The overall incidence has been falling perhaps due to screening.
The vast majority of colorectal cancers are sporadic and not familial. Epidemiologic studies demonstrate an increased risk of colorectal cancer with the following conditions/characteristics:
Family history of colorectal cancer is associated with an increased risk of developing colorectal cancer. If one first-degree family member had colorectal cancer, the risk increases 1.7-fold
Diet high in red or processed meat
Increased bowel anaerobic flora
Diabetes mellitus/insulin resistance: the risk of colon cancer may be 30% higher in diabetics compared with nondiabetics
Inflammatory bowel disease. Increased incidence is seen with both Crohn's disease and ulcerative colitis and is associated with the severity, extent, and duration of disease affecting the colon. The risk of colon cancer in ulcerative colitis is approximately 10% at 10-year duration, 20% at 20-year duration, and >35% at 30-year duration. Total colectomy eliminates the risk of colon cancer
Streptococcus bovis bacteremia
Prior pelvic radiation
Fewer than 10% of colon cancers are known to be associated with an inherited predisposition to colon cancer. The most common inherited syndromes are FAP and HNPCC. The MYH gene mutations are associated with an inherited predisposition to colon cancer as well (2).
Familial Adenomatous Polyposis (FAP)
Most cases of FAP are due to mutations in the APC gene on chromosome 5q21. These mutations are inherited in an autosomal dominant fashion.
APC is a tumor suppressor gene whose product interacts with critical cell proliferation genes in part by its interaction with transcription factor, beta catenin.
FAP is associated with hundreds to thousands of polyps throughout the colon. Fewer polyps and a later onset of colorectal cancer characterize an attenuated form of FAP. The use of COX-2 inhibitors can result in regression of some polyps.
By age 10 years, 15% of carriers will have adenomas; by age 20 years, 75% will have adenomas; and by age 30 years more than 90% will have adenomas. Screening of first-degree relatives should be done by age 10 years. Treatment is a total proctocolectomy.
FAP accounts for <1% of colon cancers and is associated with congenital hypertrophy of the retinal pigment, desmoid tumors (Gardner's syndrome), and brain tumors (Turcot's syndrome).
Hereditary Nonpolyposis Colon Cancer (HNPCC)
HNPCC is due to mutation ...