title: Increased risk of colorectal neoplasia among family members of patients with colorectal cancer: a population-based study in Utah.
abstract: OBJECTIVE
  Colorectal cancer (CRC) frequently develops in multiple members of the same families, but more data are needed to prepare effective screening guidelines. We quantified the risk of CRC and adenomas in first-degree relatives (FDRs) and second-degree relatives and first cousins of individuals with CRC, and stratified risk based on age at cancer diagnosis.
  
  
  METHODS
  We performed a case-control study of Utah residents, 50-80 years old, who underwent colonoscopy from 1995 through 2009. Index cases (exposed to colonoscopy) were colonoscopy patients with a CRC diagnosis. Age- and sex-matched individuals, unexposed to colonoscopy (controls) were selected to form the comparison groups for determining risk in relatives. Colonoscopy results were linked to cancer and pedigree information from the Utah Population Database to investigate familial aggregation of colorectal neoplasia using Cox regression analysis.
  
  
  RESULTS
  Of 126,936 patients who underwent a colonoscopy, 3804 were diagnosed with CRC and defined the index cases. FDRs had an increased risk of CRC (hazard rate ratio [HRR], 1.79; 95% confidence interval [CI],1.59-2.03), as did second-degree relatives (HRR, 1.32; 95% CI, 1.19-1.47) and first cousins (HRR, 1.15; 95% CI, 1.07-1.25), compared with relatives of controls. This risk was greater for FDRs when index patients developed CRC at younger than age 60 years (HRR, 2.11; 95% CI, 1.70-2.63), compared with older than age 60 years (HRR, 1.77; 95% CI, 1.58-1.99). The risk of adenomas (HRR, 1.82; 95% CI, 1.66-2.00) and adenomas with villous histology (HRR, 2.43; 95% CI, 1.96-3.01) also were increased in FDRs. Three percent of CRCs in FDRs would have been missed if the current guidelines, which stratify screening recommendations by the age of the proband, were strictly followed.
  
  
  CONCLUSIONS
  FDRs, second-degree relatives, and first cousins of patients who undergo colonoscopy and are found to have CRC have a significant increase in the risk of colorectal neoplasia. These data should be considered when establishing CRC screening guidelines for individuals and families.
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah; Division of Gastroenterology, University of Utah, Salt Lake City, Utah. Electronic address: Jewel.samadder@hsc.utah.edu.
authors.forename: N Jewel
authors.initials: NJ
authors.lastname: Samadder
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah; Division of Genetic Epidemiology, Department of Medicine, University of Utah, Salt Lake City, Utah.
authors.forename: Karen
authors.initials: K
authors.lastname: Curtin
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
authors.forename: Thérèse M F
authors.initials: TM
authors.lastname: Tuohy
authors.affiliation: Department of Oncology, Intermountain Healthcare, Salt Lake City, Utah.
authors.forename: Kerry G
authors.initials: KG
authors.lastname: Rowe
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah; Department of Oncological Sciences, University of Utah, Salt Lake City, Utah.
authors.forename: Geraldine P
authors.initials: GP
authors.lastname: Mineau
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
authors.forename: Ken R
authors.initials: KR
authors.lastname: Smith
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
authors.forename: Richard
authors.initials: R
authors.lastname: Pimentel
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
authors.forename: Jathine
authors.initials: J
authors.lastname: Wong
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
authors.forename: Ken
authors.initials: K
authors.lastname: Boucher
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah; Division of Gastroenterology, University of Utah, Salt Lake City, Utah; Department of Oncological Sciences, University of Utah, Salt Lake City, Utah.
authors.forename: Randall W
authors.initials: RW
authors.lastname: Burt
mesh_terms: D000236:Adenoma / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D055088:Early Detection of Cancer; D005260:Female; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D014589:Utah / Q000453:epidemiology
keywords: Adenomatous Polyps; Colon Cancer; Genetic; Recurrence Risk