Every time I come across the statistics of colon cancer, I reach for my antacid medicine. Colon cancer is the second-leading cause of cancer death. This year, there will be 165,000 new cases and more than 52,000 deaths in the U.S.; more than 95% of those are totally unnecessary.

 

The natural history of colon cancer

What causes colon cancer? We know that in order for a cell of the lining of the colon (epithelial cell) to turn malignant, it has to accumulate at least 5 specific mutations. In fact, this process of mutation accumulation is very slow, measured in decades. The first mutation may simply cause an abnormal looking mucosa (another name for the lining of the colon) due to hyperproliferation. As further mutations accumulate, this abnormality develops into a small polyp, less than 1cm, still benign. As the polyp grows bigger (>1cm) it may begin to harbor malignant cells, which eventually develop into an invasive tumor. But even then, not all polyps develop into malignant tumors. Studies on the natural history of untreated polyps larger than 1cm showed that the risk of progression to cancer is 2.5% at 5 years, 8% at 10 years, and 24% at 20 years.

Some colon cancers, such as hereditary non-polyposis colorectal cancer (HNPCC) and familial adenomatosis polyposis (FAP), are genetically determined and do not go through the slow process of mutation accumulation. Other conditions, such as Crohn’s disease and ulcerative colitis (both inflammatory bowel diseases), have an increased risk of colorectal cancer. But these conditions make up only a small percentage of the total incidence of colon cancer (about 1-2%). Environmental effects seem to be the major determinant in the formation of polyps in most of us. What are they?

  • At least 150 studies conducted since the early 1980s have suggested that people who consistently consume large amounts of fruits and vegetables are half as likely to develop cancer as people whose diets lack fruits and vegetables.
  • A diet rich in animal fat is associated with an elevated risk of colon cancer. Although the mechanism for that is not completely understood, some explanations make sense. For instance, absorption of fat requires the secretion of bile acid into the gut. Bile acids are known to be mutagenic (mutation-causing) and a high bile acid content in the stool correlates with increased risk of colon cancer. Several large studies have shown that calcium supplementation (700mg per day) can cut the incidence of polyps in men by 50% and in women by about 25%. Other studies used supplementation of 1,000mg a day, showing a similar effect.

What about aspirin and other non-steroidal anti-inflammatory drugs (ibuprofen, Advil, and similar drugs)? Here is a quote from the National Cancer Institute website:

“There is inadequate evidence that the use of NSAIDs (nonsteroidal anti-inflammatory drugs) reduces the risk of CRC (colorectal cancer).”

Based on solid evidence, NSAIDs reduce the risk of adenomas, but the extent to which this translates into a reduction of colorectal cancer is uncertain.

  • Obesity has been shown to correlate with a higher risk of colon cancer.
  • Sedentary lifestyle is correlated with elevation of colon cancer risk.

So this first line of defense, changes in our dietary and activity habits, can reduce your risk of colon cancer by more than 50%. Impressive, indeed, but how do we get from here to zero risk of cancer, or close to it?

 

The second line of defense

Suppose we do all these wonderful things, yet those dreaded mutations still occur. Is all lost? The answer is a resounding NO!

As I mentioned, the process of polyp formation is extremely slow and can take decades. Fortunately, we have years to intercept it before it turns malignant. Here are the recommendations of the USPSTF (U.S. Preventive Services Task Force).

  • The USPSTF recommends initiating screening at 50 years of age for men and women at average risk for colorectal cancer, based on the incidence of cancer above this age in the general population. In persons at higher risk (for example, those with a first-degree relative who receives a diagnosis with colorectal cancer before 60 years of age), initiating screening at an earlier age is reasonable.
  • The USPSTF found good evidence that periodic fecal occult blood testing (FOBT) reduces mortality from colorectal cancer. The task force recommends that the test will be done every 1-2 years (Annual FOBT offers greater reductions in mortality rates than biennial screening but produces more false-positive results).
  • A 10-year interval has been recommended for colonoscopy on the basis of evidence regarding the natural history of adenomatous polyps. The National Polyp Study, a randomized trial of different intervals of surveillance after polypectomy, estimated that 76% to 90% of cancers could be prevented by regular colonoscopic surveillance exams.
  • Shorter intervals (5 years) have been recommended for flexible sigmoidoscopy and double-contrast barium enema because of their lower sensitivity. First-time sigmoidoscopic screening detects approximately 7 cancers and about 60 large or high-risk polyps per 1,000 examinations. Although sigmoidoscopy can only visualize the lower half of the colon, it has been estimated to identify 80% of all patients with significant findings in the colon, because findings on sigmoidoscopy will trigger an examination of the entire colon.
  • The greatest reduction in mortality has been shown by a combination of annual or biannual FOBT, and sigmoidoscopy every 5 years or colonoscopy every 10 years.

 

What to do now?

On a personal level, the answer is obvious: Eat well, exercise, and see your doctor annually for a screening test.

On the national level, though, there are only questions. Here is a disease that costs 50,000 lives every year, costs billions of dollars a year in treatment alone, not counting lost productivity, and what are we doing about it? Can’t we get past the ideological and narrow self-interest considerations and just start solving problems that are real, and eminently solvable? Are our political, medical, and business leaderships that cynical and callous?

I can’t end on such a negative note, so here is a ray of light in this dismal picture. I belong to Kaiser Permanente Northern California, a not-for-profit HMO. I get my annual physical yearly without fail; my super conscientious and superbly well-informed primary care physician, Dr. J.P. (name withheld for my own self-interest; it will become tough to get an appointment), will bring up on the computer screen my medical history, will discuss it with me and will actually listen to all my health concerns, will perform the physical exam, including the prostate exam (no great joy for me or for her, I’m sure), will order the routine lab tests, and will refer me to specialists, if necessary. I never have to worry about remembering the time for colonoscopy—she and the computer are on top of that. I never have to worry about extra costs to see a gastroenterologist or a dermatologist. In fact, my health and well-being are the least of my concerns. I have the feeling that I am in competent hands. Why can’t everybody get such care? Isn’t that how medicine should be?

Dov Michaeli, MD, PhD
Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.