Detecting and preventing colorectal cancer in specific communities.

The prevention of cancer and cancer mortality, when possible, are now the duties of all physicians. To help them do so effectively, data from national studies should be supplemented by information concerning cancer incidence, availability and utilization of screening, and risk and protective factors within specific communities. The detailed and careful analysis of these aspects of colorectal cancer (CRC) in each of Kentucky's 15 Area Development Districts (ADD's) by Hopenhayn et al and published in this issue of the Journal reveals interesting local differences in these parameters.

CRC is one of the few neoplasms for which the efficacy of secondary prevention by screening is proven. Fecal occult blood testing and colonoscopy facilitate the detection and removal of premalignant polyps and have been clearly shown to decrease mortality by discovering CRC at an early stage. These investigators also found a strong positive correlation between periodic health evaluation and CRC incidence.

Fiber consumption and exercise are thought to protect against CRC; high fat or alcohol intake and tobacco smoking are considered risk factors. (1) Yet CRC incidence was lowest in just those ADDs with the highest incidence of risk factors. The authors plausibly explain this unexpected result by another observation: residents of ADDs with the healthiest habits were most likely to participate in periodic screening for CRC, so that more tumors were found among them. CRC mortality may have been higher in groups that were not screened, but this parameter was not evaluated.

The authors' explanation may be valid, but the result does not support a strong role for environmental factors in CRC pathogenesis, comparable to that of tobacco smoking for respiratory tract neoplasia, for example. The results of the largest prospective study of the ability of dietary fiber to prevent CRC and polyps were negative. (2,3) The present study suggests that we cannot, with confidence, tell our patients how to prevent CRC. Physicians in those ADDs where screening is not readily available, or is underutilized, must seek remedies for these deficiencies in health care. Ad hoc screening of all patients more than 50 years of age is justified. More focused screening of the groups at highest risk for CRC might be even more productive. Environmental factors do not yet clearly define such groups, but identifying genetic risks may help us to protect the most vulnerable.

The existence of germline mutations causing CRC is suggested by the occurrence of CRC in patients less than 50 years of age, and in first-degree relative clusters. The paradigm of heritable CRC is familial adenomatous polyposis coli (APC), in which mutations of the APC gene on chromosome arm 5q cause the development of many of the polyps found in patients under the age of 30. Mismatch repair gene mutations lead to the familial nonpolyposis (Lynch) colon cancer syndromes; with APC they account for as much as 5% of all CRC. Known as attenuated APC (AAPC), APC mutations have now been defined which only induce CRC in mid-adult life, or even old age, and cause far fewer polyps. (4) Because of the late onset of AAPC-related CRC, such genetic risk factors may not be recognized.

Large-scale genetic screening for these germline mutations is not yet available; but if any adult's family history reveals first-degree relatives with CRC, periodic colonoscopy should be initiated at 40 rather than 50 years of age. Conversely, the first-degree relatives of any patient with proven CRC should be considered at-risk, and should be encouraged to have periodic colonoscopic examinations. According to one study, AAPC mutations were found to occur in up to 6% of a particular population. (4) They should be considered in any group with a high incidence of CRC. Although cyclooxygenase inhibitors such as aspirin can reduce polyp formation in APC patients, their value for preventing CRC in large populations has not been demonstrated. (5) They may, however, be of value among those with proven or probable AAPC mutations. Focused screening, guided by family history, may be the best approach to reducing CRC mortality.

Accepted November 5, 2003

Copyright [c] 2004 by The Southern Medical Association

0038-4348/04/9700-0215

References

1. Matzakos T, Lawrence SP, Ahnen DJ. Epidemiology and risk factors for colo-rectal cancer. [Up To Date Online Website] July 23, 2003. Available at www.uptodateonline.com. Accessed January 27, 2004.

2. Fuchs CS, Giovannucci EL, Colditz GA, Hunter DJ et al. Dietary fiber and the risk of colorectal cancer and adenoma in women. New Eng J Med 1999;340:169-176.

3. Potter JD. Fiber and colorectal cancer--Where to now? New Eng J Med 1999;340:223-224.

4. Laken SJ, Peterson GM, Gruber SB, Oddoux C, et al. Familial colorectal cancer in Ashkenazim due to a hypermutable tract in APC. Nature Genetics 1997;17:79-83.

5. Janne PA, Mayer RJ. Chemoprevention of colorectal cancer. New Eng J Med 2000;342:1960.

Albert S. Braverman, MD, FACP 

From the Division of Hematology and Oncology, Downstate Medical College, State University of New York, Brooklyn, NY.

Reprint requests to Albert S. Braverman, MD, FACP, Division of Hematology and Oncology, Downstate Medical College at Brooklyn, Box 55, 450 Clarkson Avenue, Brooklyn, NY 11203-2098. Email: [e-mail]