title: A model to determine colorectal cancer risk using common genetic susceptibility loci.
abstract: OBJECTIVE
  Risk for colorectal cancer (CRC) can be greatly reduced through screening. To aid in the development of screening strategies, we refined models designed to determine risk of CRC by incorporating information from common genetic susceptibility loci.
  
  
  METHODS
  By using data collected from more than 12,000 participants in 6 studies performed from 1990 through 2011 in the United States and Germany, we developed risk determination models based on sex, age, family history, genetic risk score (number of risk alleles carried at 27 validated common CRC susceptibility loci), and history of endoscopic examinations. The model was validated using data collected from approximately 1800 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, conducted from 1993 through 2001 in the United States.
  
  
  RESULTS
  We identified a CRC genetic risk score that independently predicted which patients in the training set would develop CRC. Compared with determination of risk based only on family history, adding the genetic risk score increased the discriminatory accuracy from 0.51 to 0.59 (P = .0028) for men and from 0.52 to 0.56 (P = .14) for women. We calculated age- and sex-specific 10-year CRC absolute risk estimates based on the number of risk alleles, family history, and history of endoscopic examinations. A model that included a genetic risk score better determined the recommended starting age for screening in subjects with and without family histories of CRC. The starting age for high-risk men (family history of CRC and genetic risk score, 90%) was 42 years, and for low-risk men (no family history of CRC and genetic risk score, 10%) was 52 years. For men with no family history and a high genetic risk score (90%), the starting age would be 47 years; this is an intermediate value that is 5 years earlier than it would be for men with a genetic risk score of 10%. Similar trends were observed in women.
  
  
  CONCLUSIONS
  By incorporating information on CRC risk alleles, we created a model to determine the risk for CRC more accurately. This model might be used to develop screening and prevention strategies.
authors: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. Electronic address: lih@fhcrc.org.
authors: Li
authors: L
authors: Hsu
authors: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Jihyoun
authors: J
authors: Jeon
authors: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany; German Cancer Consortium, Heidelberg, Germany.
authors: Hermann
authors: H
authors: Brenner
authors: University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California.
authors: Stephen B
authors: SB
authors: Gruber
authors: Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors: Robert E
authors: RE
authors: Schoen
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland.
authors: Sonja I
authors: SI
authors: Berndt
authors: Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Andrew T
authors: AT
authors: Chan
authors: Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
authors: Jenny
authors: J
authors: Chang-Claude
authors: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Mengmeng
authors: M
authors: Du
authors: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Jian
authors: J
authors: Gong
authors: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Tabitha A
authors: TA
authors: Harrison
authors: Division of Epidemiology, Department of Population Health, New York University School of Medicine, New York, New York.
authors: Richard B
authors: RB
authors: Hayes
authors: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
authors: Michael
authors: M
authors: Hoffmeister
authors: Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland.
authors: Carolyn M
authors: CM
authors: Hutter
authors: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Yi
authors: Y
authors: Lin
authors: Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: Reiko
authors: R
authors: Nishihara
authors: Department of Pathology, Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
authors: Shuji
authors: S
authors: Ogino
authors: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Ross L
authors: RL
authors: Prentice
authors: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors: Fredrick R
authors: FR
authors: Schumacher
authors: Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland.
authors: Daniela
authors: D
authors: Seminara
authors: Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah.
authors: Martha L
authors: ML
authors: Slattery
authors: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors: Duncan C
authors: DC
authors: Thomas
authors: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Mark
authors: M
authors: Thornquist
authors: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Polly A
authors: PA
authors: Newcomb
authors: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Centre for Public Health Research, Massey University, Wellington, New Zealand.
authors: John D
authors: JD
authors: Potter
authors: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Yingye
authors: Y
authors: Zheng
authors: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Emily
authors: E
authors: White
authors: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. Electronic address: upeters@fhcrc.org.
authors: Ulrike
authors: U
authors: Peters
mesh_terms: D000367:Age Factors; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D003661:Decision Support Techniques; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005858:Germany; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D015233:Models, Statistical; D016017:Odds Ratio; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D014481:United States
chemical_list: D014408:Biomarkers, Tumor
keywords: Colorectal Cancer Screening; Genome-Wide Association Study; Risk Determination; Risk Stratification