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

Mark A. Jenkins, Aung K. Win, James G. Dowty, Robert J. MacInnis, Enes Makalic, Daniel F. Schmidt, Gillian S. Dite, Mirosl Kapuscinski, Mark Clendenning, Christophe Rosty, Ingrid M. Winship, Jon D. Emery, Sibel Saya, Finlay A. Macrae, Dennis J. Ahnen, David Duggan, Jane C. Figueiredo, Noralane M. Lindor, Robert W. Haile, John D. Potter & 6 others Michelle Cotterchio, Steven Gallinger, Polly A. Newcomb, Daniel D. Buchanan, Graham Casey, John L. Hopper

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
JournalFamilial Cancer
DOIs
Publication statusAccepted/In press - 17 Jun 2019
Externally publishedYes

Keywords

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

Cite this

Jenkins, Mark A. ; Win, Aung K. ; Dowty, James G. ; MacInnis, Robert J. ; Makalic, Enes ; Schmidt, Daniel F. ; Dite, Gillian S. ; Kapuscinski, Mirosl ; Clendenning, Mark ; Rosty, Christophe ; Winship, Ingrid M. ; Emery, Jon D. ; Saya, Sibel ; Macrae, Finlay A. ; Ahnen, Dennis J. ; Duggan, David ; Figueiredo, Jane C. ; Lindor, Noralane M. ; Haile, Robert W. ; Potter, John D. ; Cotterchio, Michelle ; Gallinger, Steven ; Newcomb, Polly A. ; Buchanan, Daniel D. ; Casey, Graham ; Hopper, John L. / Ability of known susceptibility SNPs to predict colorectal cancer risk for persons with and without a family history. In: Familial Cancer. 2019.
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title = "Ability of known susceptibility SNPs to predict colorectal cancer risk for persons with and without a family history",
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",
author = "Jenkins, {Mark A.} and Win, {Aung K.} and Dowty, {James G.} and MacInnis, {Robert J.} and Enes Makalic and Schmidt, {Daniel F.} and Dite, {Gillian S.} and Mirosl Kapuscinski and Mark Clendenning and Christophe Rosty and Winship, {Ingrid M.} and Emery, {Jon D.} and Sibel Saya and Macrae, {Finlay A.} and Ahnen, {Dennis J.} and David Duggan and Figueiredo, {Jane C.} and Lindor, {Noralane M.} and Haile, {Robert W.} and Potter, {John D.} and Michelle Cotterchio and Steven Gallinger and Newcomb, {Polly A.} and Buchanan, {Daniel D.} and Graham Casey and Hopper, {John L.}",
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month = "6",
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doi = "10.1007/s10689-019-00136-6",
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Jenkins, MA, Win, AK, Dowty, JG, MacInnis, RJ, Makalic, E, Schmidt, DF, Dite, GS, Kapuscinski, M, Clendenning, M, Rosty, C, Winship, IM, Emery, JD, Saya, S, Macrae, FA, Ahnen, DJ, Duggan, D, Figueiredo, JC, Lindor, NM, Haile, RW, Potter, JD, Cotterchio, M, Gallinger, S, Newcomb, PA, Buchanan, DD, Casey, G & Hopper, JL 2019, 'Ability of known susceptibility SNPs to predict colorectal cancer risk for persons with and without a family history', Familial Cancer. https://doi.org/10.1007/s10689-019-00136-6

Ability of known susceptibility SNPs to predict colorectal cancer risk for persons with and without a family history. / Jenkins, Mark A.; Win, Aung K.; Dowty, James G.; MacInnis, Robert J.; Makalic, Enes; Schmidt, Daniel F.; Dite, Gillian S.; Kapuscinski, Mirosl; Clendenning, Mark; Rosty, Christophe; Winship, Ingrid M.; Emery, Jon D.; Saya, Sibel; Macrae, Finlay A.; Ahnen, Dennis J.; Duggan, David; Figueiredo, Jane C.; Lindor, Noralane M.; Haile, Robert W.; Potter, John D.; Cotterchio, Michelle; Gallinger, Steven; Newcomb, Polly A.; Buchanan, Daniel D.; Casey, Graham; Hopper, John L.

In: Familial Cancer, 17.06.2019.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Ability of known susceptibility SNPs to predict colorectal cancer risk for persons with and without a family history

AU - Jenkins, Mark A.

AU - Win, Aung K.

AU - Dowty, James G.

AU - MacInnis, Robert J.

AU - Makalic, Enes

AU - Schmidt, Daniel F.

AU - Dite, Gillian S.

AU - Kapuscinski, Mirosl

AU - Clendenning, Mark

AU - Rosty, Christophe

AU - Winship, Ingrid M.

AU - Emery, Jon D.

AU - Saya, Sibel

AU - Macrae, Finlay A.

AU - Ahnen, Dennis J.

AU - Duggan, David

AU - Figueiredo, Jane C.

AU - Lindor, Noralane M.

AU - Haile, Robert W.

AU - Potter, John D.

AU - Cotterchio, Michelle

AU - Gallinger, Steven

AU - Newcomb, Polly A.

AU - Buchanan, Daniel D.

AU - Casey, Graham

AU - Hopper, John L.

PY - 2019/6/17

Y1 - 2019/6/17

N2 - 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.

AB - 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.

KW - Colorectal cancer

KW - Family history

KW - Prediction model

KW - Risk prediction

KW - Single nucleotide polymorphism

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U2 - 10.1007/s10689-019-00136-6

DO - 10.1007/s10689-019-00136-6

M3 - Article

JO - Familial Cancer

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