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Fam Cancer. 2019 Jun 17. doi: 10.1007/s10689-019-00136-6. [Epub ahead of print]

Ability of known susceptibility SNPs to predict colorectal cancer risk for persons with and without a family history.

Author information

1
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, 3010, Australia. m.jenkins@unimelb.edu.au.
2
Centre for Cancer Research, The University of Melbourne, Parkville, VIC, Australia. m.jenkins@unimelb.edu.au.
3
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, 3010, Australia.
4
Centre for Cancer Research, The University of Melbourne, Parkville, VIC, Australia.
5
Genetic Medicine, Royal Melbourne Hospital, Parkville, VIC, Australia.
6
Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia.
7
Colorectal Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia.
8
Envoi Specialist Pathologists, Herston, QLD, Australia.
9
School of Medicine, University of Queensland, Herston, QLD, Australia.
10
Department of Medicine, The University of Melbourne, Parkville, VIC, Australia.
11
Department of General Practice, Centre for Cancer Research, University of Melbourne, Parkville, VIC, Australia.
12
The Primary Care Unit, Department of Public Health & Primary Care, University of Cambridge, Cambridge, UK.
13
Colorectal Medicine and Genetics, Royal Melbourne Hospital, Parkville, VIC, Australia.
14
University of Colorado School of Medicine, Denver, CO, USA.
15
Office of the Chief Operating Officer, Translational Genomics Research Institute, Phoenix, AZ, USA.
16
Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
17
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
18
Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ, USA.
19
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
20
School of Public Health, University of Washington, Seattle, WA, USA.
21
Centre for Public Health Research, Massey University, Wellington, New Zealand.
22
Cancer Care Ontario, Toronto, ON, Canada.
23
Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
24
Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.

Abstract

Before SNP-based risk can be incorporated in colorectal cancer (CRC) screening, the ability of these SNPs to estimate CRC risk for persons with and without a family history of CRC, and the screening implications need to be determined. We estimated the association with CRC of a 45 SNP-based risk using 1181 cases and 999 controls, and its correlation with CRC risk predicted from detailed family history. We estimated the predicted change in the distribution across predefined risk categories, and implications for recommended screening commencement age, from adding SNP-based risk to family history. The inter-quintile risk ratio for colorectal cancer risk of the SNP-based risk was 3.28 (95% CI 2.54-4.22). SNP-based and family history-based risks were not correlated (r = 0.02). For persons with no first-degree relatives with CRC, screening could commence 4 years earlier for women (5 years for men) in the highest quintile of SNP-based risk. For persons with two first-degree relatives with CRC, screening could commence 16 years earlier for men and women in the highest quintile, and 7 years earlier for the lowest quintile. This 45 SNP panel in conjunction with family history, can identify people who could benefit from earlier screening. Risk reclassification by 45 SNPs could inform targeted screening for CRC prevention, particularly in clinical genetics settings when mutations in high-risk genes cannot be identified. Yet to be determined is cost-effectiveness, resources requirements, community, patient and clinician acceptance, and feasibility with potentially ethical, legal and insurance implications.

KEYWORDS:

Colorectal cancer; Family history; Prediction model; Risk prediction; Single nucleotide polymorphism

PMID:
31209717
DOI:
10.1007/s10689-019-00136-6

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