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A model to determine colorectal cancer risk using common genetic susceptibility loci.
- Source :
-
Gastroenterology [Gastroenterology] 2015 Jun; Vol. 148 (7), pp. 1330-9.e14. Date of Electronic Publication: 2015 Feb 13. - Publication Year :
- 2015
-
Abstract
- Background & Aims: 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.<br />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.<br />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.<br />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.<br /> (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Age Factors
Case-Control Studies
Colonoscopy
Colorectal Neoplasms pathology
Decision Support Techniques
Female
Gene Frequency
Genetic Predisposition to Disease
Genome-Wide Association Study
Germany
Humans
Logistic Models
Male
Middle Aged
Odds Ratio
Pedigree
Phenotype
Prognosis
Reproducibility of Results
Risk Assessment
Risk Factors
Sex Factors
United States
Biomarkers, Tumor genetics
Colorectal Neoplasms genetics
Genetic Loci
Models, Genetic
Models, Statistical
Polymorphism, Single Nucleotide
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0012
- Volume :
- 148
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 25683114
- Full Text :
- https://doi.org/10.1053/j.gastro.2015.02.010