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.
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.
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.