Current issues of ACP Journal Club are published in Annals of Internal Medicine


Risk for colorectal cancer was more precisely defined for those with a positive family history

ACP J Club. 1995 May-June;122:82. doi:10.7326/ACPJC-1995-122-3-082

Source Citation

Fuchs CS, Giovannucci EL, Colditz GA, et al. A prospective study of family history and the risk of colorectal cancer. N Engl J Med. 1994 Dec 22;331:1669-74.



To determine the strength of the association between the risk for colorectal cancer and a family history of colorectal cancer.


Data from 2 study cohorts: The Nurses' Health Study, begun in 1976, and the Health Professionals Follow-up Study, begun in 1986.


Community-based study.


121 700 women in the Nurses' Health Study and 51 269 men in the Health Professionals Follow-up Study were mailed questionnaires every 2 years that requested information on cancer and coronary heart disease, including information about food consumption and supplemental vitamin use. Exclusion criteria were ≥ 10 nonresponses on food questions, previous cancer, ulcerative colitis, familial polyposis syndrome, nonresponse to endoscopy question by men, and previous colonoscopy or sigmoidoscopy. Data for 87 031 women (mean age 50 y) and 32 085 men (mean age 53 y) were eligible for analysis.

Assessment of risk factors

Colorectal cancer in a father, mother, sister, or brother.

Main outcome measure

Age-adjusted relative risk for colorectal cancer.

Main results

Colorectal cancer was diagnosed in 315 of the women and 148 of the men; 17% of these participants had a family history of colorectal cancer. The age-adjusted relative risk (RR) for colorectal cancer among women with a family history was 1.77 (95% CI 1.32 to 2.37); for men it was 1.64 (CI 1.04 to 2.58). The strength of the association was not altered by multivariate adjustment for known or suspected environmental risk factors. The age-adjusted risk was highest for participants < 45 years of age with a family history of colorectal cancer (RR for participants < 45 y, 5.37; CI 1.98 to 14.6; P for trend < 0.001) and for participants with 2 affected relatives (RR 2.75, CI 1.34 to 5.63, P for trend < 0.001).


In 2 separate study cohorts, an increased risk for colorectal cancer was noted among participants with a family history of colorectal cancer. The age-adjusted risk was greatest for participants < 45 years of age and for participants who had at least 2 relatives with colorectal cancer.

Source of funding: National Institutes of Health.

For article reprint: Dr. C.S. Fuchs, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA. FAX 617-632-5370.


Population studies suggest that a history of colorectal cancer in first-degree relatives is a risk factor for colorectal carcinoma (1). The magnitude of risk is approximately 2-fold with disease in 1 first-degree relative and 3-fold with disease in 2 first-degree relatives. Population studies, however, may overestimate the risk because of recall bias. The results of the cohort study by Fuchs and colleagues were not affected by recall bias and support the previously reported magnitude of relative risk.

This study may actually underestimate the risk associated with a positive family history because many participants who had had a previous sigmoidoscopy or colonoscopy were appropriately excluded from the analysis. Many of these participants had a positive family history and, if these participants at higher risk had been included, the relative risk of a positive family history may have been higher.

The bottom line: Patients with a positive family history of colorectal cancer have a small increased risk for developing colorectal carcinoma. The main unresolved issue: What screening is indicated for these patients? The American College of Physicians and the World Health Organization suggest that these patients at higher risk begin standard screening programs with sigmoidoscopy at age 40 (2) or even that they have colonoscopy or barium enema every 5 years (3). The finding of this study that patients < 45 years of age have the higher age-adjusted risk supports these guidelines. These guidelines, however, have not been validated by prospective outcomes research and will almost certainly change when genetic markers for colorectal adenomas become widely available, allowing more accurate identification of patients at higher risk.

Philip S. Schoenfeld, MD, MSEd
National Naval Medical CenterBethesda, Maryland, USA


1. Bishop DT, Thomas HJ. The genetics of colorectal cancer. Cancer Surv. 1990;9:585-604.

2. Burt RW, Bishop DT, Lynch HT, Rozen P, Winawer SJ. Risk and surveillance of individuals with heritable factors for colorectal cancer. WHO Collaborating Centre for the Prevention of Colorectal Cancer. Bull World Health Organ. 1990;68:655-65.

3. Eddy DM. Screening for colorectal cancer. Ann Intern Med. 1990;113:373-84.