DR. GIL VILLANUEVA

Colorectal Cancer (CRC)1) Epidemiology and Risk Factors 2) Molecular biology and Pathophysiology 3) Symptoms and Stages 4) Screening 5) Therapy

Function of the Colon and Rectumy The colon and rectum comprise the large intestine (large bowel) y The primary function of the large bowel is to turn liquid stool into formed fecal matter

Colorectal Cancery A disease in which normal cells in the lining of the colon or rectum begin to change and grow without control

y Usually begins as a noncancerous polyp that can, over time, become a cancerous tumor

EPIDEMIOLOGYy one of the most common cancers in the world

US:

4th most common cancer(after lung, prostate, and breast cancers)

2nd most common cause of cancer death(after lung cancer)

y Nearly equal sex distribution (slight male preponderance) y Age: Mean 63 years

Typical sites of incidence and symptoms of colon cancer

Molecular Biology & Pathologyy CRCs arise from a series of histopathological and molecular changes

that transform normal epithelial cellsy Intermediate step is the adenomatous polyp y Adenoma-Carcinoma-Sequence (Vogelstein & Kinzler) y Polyps occur universally in FAP, but FAP accounts for only 1% of

CRCsy Adenomatous Polyps in general population:

33% at age 50 70% at age 70

Changes resulting in colon cancer Changes resulting in colon cancer

Colon cancers result from a series of pathologic changes that transform normal colonic epithelium into invasive carcinoma. Specific genetic events, shown by vertical arrows, accompany this multistep process. The various chemopreventive agents exert their effects at different steps in this pathway, and this is depicted on the basis of the available epidemiologic evidence, the results of studies in animals, and the known mechanisms of action of the agents.

Development of CRCy result of interplay between environmental and genetic factors y Central environmental factors:

diet and lifestyle 35% of all cancers are attributable to diet 50%-75% of CRC may be preventable through dietary modifications

Risk factors for CRCy Age y Adenomas, Polyps y Sedentary lifestyle, Diet, Obesity y Family History of CRC y Inflammatory Bowel Disease (IBD) y Hereditary Syndromes y familial adenomatous polyposis (FAP) y HNPCC

Polypsy 95% of CRC arise from benign adenomas y Sessile or pedunculated y Tubular or villous y Increase malignant transformation risk with:y Size y Villous component y Dysplasia

Familial Adenomatous Polypy Autosomal dominant y Germ line mutation in APC gene (5q) y Polyps start to appear in the teen age y The colon becomes full of polyps y Cancer usually occurs in the 4 th decade y Rx. Surgery

FAMILIAL POLYPOSIS

Hereditary Colorectal Cancer Syndromes: HNPCCy Lynch Syndrome y Accounts to approximately 5-10% of colorectal cancer cases y The risk of colorectal cancer in families with HNPCC is 70-90% y People with HNPCC are diagnosed with colorectal cancer at an average age of 45 years old

Dietary Factors Associated with Colorectal Carcinogenesis

y consumption of red meat y animal and saturated fat

y increased risky refined carbohydrates y alcohol

Dietary Factors Associated with Colorectal Carcinogenesisy dietary fiber y vegetables y fruits

decreased risk

y antioxidant vitamins y calcium y folate (B Vitamin)

ADENOCARCINOMA OF THE RECTOSIGMOID AREA

EXOPHYTIC ADENOCARCINOMA OF THE CECUM

Symptoms associated with CRCy weight loss y loss of appetite y night sweats y fever y rectal bleeding y change in bowel habits y obstruction y abdominal pain & mass y iron-deficiency anemia

Staging of CRCy TNM system

Primary tumor (T) Regional lymph nodes (N) Distant metastasis (M)

Staging of CRCy Dukes staging system

A Mucosa B Into or through M. propria C1 Into M. propria, + LN C2 Through M. propria, + LN D distant metastatic spread

80% 50% 40% 12%