BACKGROUND AND AIMS:

Little is known about the change in risk conferred by family history of colorectal cancer (CRC) as a person ages. We evaluated the effect of family history on CRC incidence and mortality after age 55 y, when the risk of early onset cancer had passed.

METHODS:

We collected data from participants in the randomized, controlled Prostate, Lung, Colorectal and Ovarian cancer screening trial of flexible sigmoidoscopy vs usual care (55-74 y old, no history of CRC), performed at 10 US centers from 1993 to 2001. A detailed family history of colorectal cancer was obtained at enrollment and subjects were followed for CRC incidence and mortality for up to 13 years.

RESULTS:

Among 144,768 participants, 14,961 (10.3%) reported a family of CRC. Of 2090 incident cases, 273 had a family history of CRC (13.1%); among 538 deaths from CRC, 71 (13.2%) had a family history of CRC. Overall, family history of CRC was associated with an increased risk of CRC incidence (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.10-1.50; P<.0001) and increased mortality (HR, 1.31; 95% CI, 1.02-1.69; P=.03). Subjects with 1 first-degree relative (FDR) with CRC (n=238; HR, 1.23; 95% CI, 1.07-1.42) or ≥2 FDRs with CRC (n=35; HR, 2.04; 95% CI, 1.44-2.86) were at increased risk for incident CRC. However, among individuals with 1 FDR with CRC, there was no difference in risk based on the age at diagnosis in the FDR (for FDR age <60 y: HR, 1.27; 95% CI, 0.97-1.63; for FDR age 60-70 y: HR, 1.33; 95% CI, 1.06-1.62; for FDR >70 y: HR, 1.14; 95% CI, 0.93-1.45; Ptrend=.59).

CONCLUSION AND RELEVANCE:

After an age of 55 y, subjects with 1 FDR with CRC had only a modest increase in risk for CRC incidence and death; age of onset in the FDR was not significantly associated with risk. Individuals with ≥2 FDRs with CRC had continued increased risk in older age. Guidelines and clinical practice for subjects with a family history of CRC should be modified to align CRC testing to risk.