title: Incidence and mortality of colorectal cancer in individuals with a family history of colorectal cancer.
abstract: OBJECTIVE
  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 55 years of age, 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 versus usual care (55-74 years 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 subjects (10.3%) reported a family of CRC. Of 2090 incident cases, 273 cases (13.1%) had a family history of CRC; 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 were no differences in risk based on age at diagnosis in the FDR (for FDR <60 years of age: HR, 1.27; 95% CI, 0.97-1.63; for FDR 60-70 years of age: HR, 1.33; 95% CI, 1.06-1.62; for FDR >70 years of age: HR, 1.14; 95% CI, 0.93-1.45; P trend = .59).
  
  
  CONCLUSIONS
  After 55 years of age, 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. ClinicalTrials.gov number, NCT00002540.
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address: rschoen@pitt.edu.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Schoen
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Anthony
authors.initials: A
authors.lastname: Razzak
authors.affiliation: Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland.
authors.forename: Kelly J
authors.initials: KJ
authors.lastname: Yu
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Berndt
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Kevin
authors.initials: K
authors.lastname: Firl
authors.affiliation: Information Management Services, Inc., Rockville, Maryland.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Riley
authors.affiliation: Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Pinsky
mesh_terms: D000367:Age Factors; D000368:Aged; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000401:mortality*; D055088:Early Detection of Cancer / Q000379:methods* / Q000706:statistics & numerical data; D005190:Family; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D012307:Risk Factors; D012812:Sigmoidoscopy
keywords: Adenomatous Polyps; Colon Cancer; Genetic Risk Factors; Screening