Colorectal Cancer

(Gastroenterology 2006;130:1872-85. N Engl J Med 2006;355:2533-41. Gastrointest Endosc 2006;63:546-57. Gastroenterology 2003;124:544-60 & 2000;118:1233-34 & 1235-57. Am J Gastroenterol 2000;95:3053-63)

DEFINITION:

Colorectal cancer (CRC) includes both colon (Sporadic and Familial) and rectal cancer
- Colon cancers: adenocarcinoma ≥95%; The rest are lymphomas, malignant carcinoid, leiomyosarcomas, Kaposi’s sarcoma
- Rectal cancers: rectum is immobile, lacks serosal covering and therefore more commonly spreads contiguously by direct extension
Familial Colon Cancer Syndromes (Inherited Colon Cancer Syndromes): Gastro 2001;121:195-97 & 198-213
- Familial Adenomatous Polyposis (FAP); Autosomal dominant; Lifetime risk of CRC 100%; Sporadic cases (patient first in family to develop FAP) 30%
  - Extracolonic features: fundic gland polyps, duodenal adenomas, desmoid tumors, osteomas (jaw), multiple teeth, eye disorders
  - Attenuated Adenomatous Polyposis Coli (AAPC): later onset, CRC ˜ age 50, fewer adenomas (right sided)
  - Gardner’s Syndrome (FAP with extracolonic manifestations, above)
  - ↑ risk of cancers: thyroid, pancreatic, duodenal, ampullary, gastric
- Hereditary Nonpolyposis Colorectal Cancer (HNPCC); Autosomal dominant; Lifetime risk CRC (most right side) 80%
  - ‘Nonpolyposis’ is misleading, really should use: Lynch Syndrome I (CRC alone), Lynch Syndrome II (CRC and other malignancies)
  - 3-2-1 rule (Amsterdam II criteria): 3 relatives with CRC (one first degree), 2 generations involved, 1 patient diagnosed <50 yrs
  - ↑ risk extracolonic cancer: endometrium (60%), Stomach (20%), Urinary (15%), Small bowel (10%), ovarian, hepatobiliary
- Hamartomatous Polyp Syndromes (Peutz-Jeghers Syndrome, Juvenile Polyposis); Autosomal dominant (STK11/LKB1 gene)
  - Mucocutaneous pigmentation; Have ↑ CRC risk (not as high as FAP) along with breast, pancreas, stomach, ovary cancer
  - Other differential in this category: Cowden’s disease and the Bannayan-Ruvalcaba-Riley syndrome

EPIDEMIOLOGY:

CRC leading cause of death in U.S., after CAD; Second leading cause of death from malignancy, after lung cancer; M = F
- Lifetime risk of CRC is 1 in 18 (5.5%); Most (75%) of people have no risk factors! New cases per year 150,000; Deaths per year 57,000
- Risk Factors:
  - Age >60, First and second degree relative with CRC or adenomas- see Screening below (lifetime risk is increased to 15% from 5.5%)
  - Environmental: ↓ Fiber, Fruits & Vegetables, ↑ Red meats, ↑ Fat, Obesity (? diabetes), ↓ physical activity, smoking, IBD after 8 yrs
- Prevalence of adenomas varies, depending on study: ranging from 20-50%
Rectal cancer accounts for 40% of CRC; Annual incidence 43,000; Annual mortality 7,000; 90% are older than 50 years (5% <40 years)

ETIOLOGIES:

	Sporadic CRC	HNPCC	FAP
Causes of CRC	65-85%	5%	1%
Mean age	69	44	39
Arise from adenoma	Yes, few	Yes, few	Yes, 100-1000’s
Distribution	Distal to splenic flex (65%)	Proximal to splenic flex (70%)	Throughout entire colon/rectum
Genetic abnormalities	Polygenic (multiple)	MSH2, MSH6, MLH1	APC
Variants	—	Lynch syndromes	Gardner’s, AAPC (1-100 polyps)
Mode of inheritance	Unknown	Autosomal dominant	Autosomal dominant
Modified from Toribara N: Colorectal cancer. In McNally P (ed): GI & Liver Secrets, 2nd ed. Philadelphia, Hanley & Belfus, 2001, pp 335.