Colorectal cancer primary prevention

Editor(s)-in-Chief: C. Michael Gibson, M.S., M.D. [mailto:mgibson@perfuse.org] Phone:617-632-7753; Elliot B. Tapper, M.D., Beth Israel Deaconess Medical Center

Overview
Most colorectal cancers should be preventable, through increased surveillance, improved lifestyle, and, probably, the use of dietary chemopreventative agents.

Surveillance
Most colorectal cancer arise from adenomatous polyps. These lesions can be detected and removed during colonoscopy. Studies show this procedure would decrease by > 80% the risk of cancer death, provided it is started by the age of 50, and repeated every 5 or 10 years.

As per current guidelines under National Comprehensive Cancer Network, in average risk individuals with negative family history of colon cancer and personal history negative for adenomas or Inflammatory Bowel diseases, flexible sigmoidoscopy every 5 years with fecal occult blood testing annually or double contrast barium enema are other options acceptable for screening rather than colonoscopy every 10 years (which is currently the Gold-Standard of care).

Lifestyle & Nutrition
The comparison of colorectal cancer incidence in various countries strongly suggests that sedentarity, overeating (i.e., high caloric intake), and perhaps a diet high in meat (red or processed) could increase the risk of colorectal cancer. In contrast, a healthy body weight, physical fitness, and good nutrition decreases cancer risk in general. Accordingly, lifestyle changes could decrease the risk of colorectal cancer as much as 60-80%.

A high intake of dietary fiber (from eating fruits, vegetables, cereals, and other high fiber food products) has, until recently, been thought to reduce the risk of colorectal cancer and adenoma. In the largest study ever to examine this theory (88,757 subjects tracked over 16 years), it has been found that a fiber rich diet does not reduce the risk of colon cancer. A 2005 meta-analysis study further supports these findings.

The Harvard School of Public Health states: "Health Effects of Eating Fiber: Long heralded as part of a healthy diet, fiber appears to reduce the risk of developing various conditions, including heart disease, diabetes, diverticular disease, and constipation. Despite what many people may think, however, fiber probably has little, if any effect on colon cancer risk."

Chemoprevention
More than 200 agents, including the above cited phytochemicals, and other food components like calcium or folic acid (a B vitamin), and NSAIDs like aspirin, are able to decrease carcinogenesis in preclinical models: Some studies show full inhibition of carcinogen-induced tumours in the colon of rats. Other studies show strong inhibition of spontaneous intestinal polyps in mutated mice (Min mice). Chemoprevention clinical trials in human volunteers have shown smaller prevention, but few intervention studies have been completed today. Calcium, aspirin and celecoxib supplements, given for 3 to 5 years after the removal of a polyp, decreased the recurrence of polyps in volunteers (by 15-40%). The "chemoprevention database" shows the results of all published scientific studies of chemopreventive agents, in people and in animals.

Aspirin chemoprophylaxis
Aspirin should not be taken routinely to prevent colorectal cancer, even in people with a family history of the disease, because the risk of bleeding and kidney failure from high dose aspirin (300mg or more) outweigh the possible benefits.

A clinical practice guideline by the U.S. Preventive Services Task Force (USPSTF) recommended against taking aspirin (grade D recommendation). The Task Force acknowledged that aspirin may reduce the incidence of colorectal cancer, but "concluded that harms outweigh the benefits of aspirin and NSAID use for the prevention of colorectal cancer". A subsequent meta-analysis concluded "300 mg or more of aspirin a day for about 5 years is effective in primary prevention of colorectal cancer in randomised controlled trials, with a latency of about 10 years". However, long-term doses over 81 mg per day may increase bleeding events.

Calcium
A meta-analysis by the Cochrane Collaboration of randomized controlled trials published through 2002 concluded "Although the evidence from two RCTs suggests that calcium supplementation might contribute to a moderate degree to the prevention of colorectal adenomatous polyps, this does not constitute sufficient evidence to recommend the general use of calcium supplements to prevent colorectal cancer.". Subsequently, one randomized controlled trial by the Women's Health Initiative (WHI) reported negative results. A second randomized controlled trial reported reduction in all cancers, but had insufficient colorectal cancers for analysis.

Vaccine
In November 2006, it was announced that a vaccine had been developed and tested with very promising results. The new vaccine, called TroVax, works in a totally different way to existing treatments by harnessing the patient's own immune system to fight the disease. Experts say this suggests that gene therapy vaccines could prove an effective treatment for a whole range of cancers. Oxford BioMedica is a British spin-out from Oxford University specializing in the development of gene-based treatments. Phase III trials are underway for renal cancers and planned for colon cancers.