Preventing Colorectal Neoplasia Methods: Means and Myths

Abstract

CN04-01

Colorectal cancer (CRC) is the third most common cause of cancer death after lung and stomach cancer, with approximately 1 million new cases and over half a million deaths, worldwide, each year. This cancer shows 20- to 30-fold variation in age-adjusted rates internationally, the age-specific rates at older ages show several hundred-fold variation, and incidence rates can change very rapidly over time. The highest rates of CRC in the world are in Japan. The degree of difference from place to place and the rapidity of change over time are explainable, not by genes, but by changes in the environment - or perhaps by their interaction.
Rare familial forms of CRC are due to deleterious mutations in known and unknown genes; nonetheless, the large majority of CRC is not associated with a known inherited genetic lesion or even a strong family history. Known environmental factors increase risk (e.g., meat, smoking) and others reduce risk (e.g., vegetables, folate, aspirin, post-menopausal hormones, calcium and vitamin D). Many less dramatic genetic changes (polymorphisms) are relevant only in the presence of environmental factors.
In 1980, we proposed that estrogens would reduce risk of colon cancer and subsequently showed that, indeed, oral contraceptives and higher parity were associated with lower risk of colon cancer. The results of the Women’s Health Initiative trial show that PMH prevents CRC: more than 2 decades from original hypothesis to confirmation in a clinical trial.
The role of aspirin and other NSAIDs in lowering risk of CRC is well established, beginning with observations in animals, through the study showing that NSAIDs were effective even in FAP patients, to the results of randomized clinical trials of prevention of metachronous polyps. NSAIDs consistently lower risk of polyps and cancer in average-, moderate-, and high-risk individuals; longer duration of use predicts lower risk; and risk resumes after use is stopped.
Despite the emergence of clear evidence for the chemopreventive capacity of specific agents, the implementation of preventive regimens is problematic because of: differences in risk in the population, determined by age, genetic inheritance, lifestyle, and history; differences between the sexes; differences in effectiveness of agents; differences in the timing of use across the lifespan; and differences in the acceptable degree of possible harm.
Primary prevention by weight control and physical activity and secondary prevention by screening, early detection, and polypectomy contribute significantly to the ability of populations and individuals to lower their risk of CRC; the duration of protection following screening by sigmoidoscopy may be as long as 15 years or more.