Cancer facts

Prevention & Treatment of Cancers

Research Projects:

Breast Cancer

Colorectal Cancer

Kidney Cancer

• Cloning of NORE1 & LSAMP
• BHD Knockout Project
• Mouse Models
• VHL
• VHL Knockout Mice
• PBRM1 Projects
• PBRM1 Knockout Mice
• VHL-PBRM1 Double Knockout Mice

BHD-FLCN papers

BHD Foundation

Myrovlytis Trus

Colorectal Cancer Projects

Introduction

Colorectal cancer, also called colon cancer or large bowel cancer, includes cancerous growths in the colon, rectum and appendix. With 655,000 deaths worldwide per year, it is the fourth most common form of cancer in the United States and the third leading cause of cancer-related death in the Western world. Colorectal cancers arise from adenomatous polyps in the colon. These mushroom-shaped growths are usually benign, but some develop into cancer over time. Localized colon cancer is usually diagnosed through colonoscopy.

Invasive cancers that are confined within the wall of the colon (TNM stages I and II) are curable with surgery. If untreated, they spread to regional lymph nodes (stage III), where up to 73% are curable by surgery and chemotherapy. Cancer that metastasizes to distant sites (stage IV) is usually not curable, although chemotherapy can extend survival, and in rare cases, surgery and chemotherapy together have seen patients through to a cure. Radiation is used with rectal cancer.

On the cellular and molecular level, colorectal cancer starts with a mutation to the Wnt signaling pathway. When Wnt binds to a receptor on the cell, that sets in motion a chain of molecular events that ends with β-catenin moving into the nucleus and activating a gene on DNA. In colorectal cancer, genes along this chain are damaged. Usually, a gene called APC, which is a "brake" on the Wnt pathway, is damaged. Without a working APC brake, the Wnt pathway is stuck in the "on" position.

Signs and symptoms

The symptoms of colorectal cancer depend on the location of tumor in the bowel, and whether it has spread elsewhere in the body (metastasis). Most of the symptoms may occur in other diseases as well, and hence none of the symptoms mentioned here is diagnostic of colorectal cancer. Symptoms and signs are divided into local, constitutional (affecting the whole body) and metastatic (caused by spread to other organs).

Risk Factors

The lifetime risk of developing colon cancer in the United States is about 7%. Certain factors increase a person's risk of developing the disease. These include:

• Age. The risk of developing colorectal cancer increases with age. Most cases occur in the 60s and 70s, while cases before age 50 are uncommon unless a family history of early colon cancer is present.
• History of cancer. Individuals who have previously been diagnosed and treated for colon cancer are at risk for developing colon cancer in the future. Women who have had cancer of the ovary, uterus, or breast are at higher risk of developing colorectal cancer.
• Heredity:
  • Family history of colon cancer, especially in a close relative before the age of 55 or multiple relatives.
  • Familial adenomatous polyposis (FAP) carries a near 100% risk of developing colorectal cancer by the age of 40 if untreated
  • Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome
  • Gardner syndrome
• Smoking. Smokers are more likely to die of colorectal cancer than non-smokers. An American Cancer Society study found that "Women who smoked were more than 40% more likely to die from colorectal cancer than women who never had smoked. Male smokers had more than a 30% increase in risk of dying from the disease compared to men who never had smoked."
• Diet. Studies show that a diet high in red meat and low in fresh fruit, vegetables, poultry and fish increases the risk of colorectal cancer. In June 2005, a study by the European Prospective Investigation into Cancer and Nutrition suggested that diets high in red and processed meat, as well as those low in fiber, are associated with an increased risk of colorectal cancer. Individuals who frequently eat fish showed a decreased risk. However, other studies have cast doubt on the claim that diets high in fiber decrease the risk of colorectal cancer; rather, low-fiber diet was associated with other risk factors, leading to confounding.The nature of the relationship between dietary fiber and risk of colorectal cancer remains controversial.
• Lithocholic acid. Lithocholic acid is a bile acid that acts as a detergent to solubilize fats for absorption. It is made from chenodeoxycholic acid by bacterial action in the colon. It has been implicated in human and experimental animal carcinogenesis. Carbonic acid type surfactant easily combine with calcium ion and become detoxication.
• Physical inactivity. People who are physically active are at lower risk of developing colorectal cancer.
• Virus. Exposure to some viruses (such as particular strains of human papilloma virus) may be associated with colorectal cancer.
• Primary sclerosing cholangitis offers a risk independent to ulcerative colitis
• Low levels of selenium.
• Inflammatory bowel disease. About one percent of colorectal cancer patients have a history of chronic ulcerative colitis. The risk of developing colorectal cancer varies inversely with the age of onset of the colitis and directly with the extent of colonic involvement and the duration of active disease. Patients with colorectal Crohn's disease have a more than average risk of colorectal cancer, but less than that of patients with ulcerative colitis.
• Environmental factors. Industrialized countries are at a relatively increased risk compared to less developed countries that traditionally had high-fiber/low-fat diets. Studies of migrant populations have revealed a role for environmental factors, particularly dietary, in the etiology of colorectal cancers.
• Exogenous hormones. The differences in the time trends in colorectal cancer in males and females could be explained by cohort effects in exposure to some gender-specific risk factor; one possibility that has been suggested is exposure to estrogens.There is, however, little evidence of an influence of endogenous hormones on the risk of colorectal cancer. In contrast, there is evidence that exogenous estrogens such as hormone replacement therapy (HRT), tamoxifen, or oral contraceptives might be associated with colorectal tumors.
• Alcohol. Drinking, especially heavily, may be a risk factor. Heavy alcohol use may also increase the risk of colorectal cancer (NCI). One study found that "People who drink more than 30 grams of alcohol per day (and especially those who drink more than 45 grams per day) appear to have a slightly higher risk for colorectal cancer." Another found that "The consumption of one or more alcoholic beverages a day at baseline was associated with approximately a 70% greater risk of colon cancer."
• Vitamin B6 intake is inversely associated with the risk of colorectal cancer