Assessment of a Polygenic Risk Score for Colorectal Cancer to Predict Risk of Lynch Syndrome Colorectal Cancer

Mark A. Jenkins; Daniel D. Buchanan; John Lai; Enes Makalic; Gillian S. Dite; Aung K. Win; Mark Clendenning; Ingrid M. Winship; Richard B. Hayes; Jeroen R. Huyghe; Ulrike Peters; Steven Gallinger; Loïc Le Marchand; Jane C. Figueiredo; Rish K. Pai; Polly A. Newcomb; James M. Church; Graham Casey; John L. Hopper

doi:10.1093/jncics/pkab022

Assessment of a Polygenic Risk Score for Colorectal Cancer to Predict Risk of Lynch Syndrome Colorectal Cancer

Mark A. Jenkins, Daniel D. Buchanan, John Lai, Enes Makalic, Gillian S. Dite, Aung K. Win, Mark Clendenning, Ingrid M. Winship, Richard B. Hayes, Jeroen R. Huyghe, Ulrike Peters, Steven Gallinger, Loïc Le Marchand, Jane C. Figueiredo, Rish K. Pai, Polly A. Newcomb, James M. Church, Graham Casey, John L. Hopper

Laboratory Medicine and Pathology

Research output: Contribution to journal › Article › peer-review

Abstract

It was not known whether the polygenic risk scores (PRSs) that predict colorectal cancer could predict colorectal cancer for people with inherited pathogenic variants in DNA mismatch repair genes - people with Lynch syndrome. We tested a PRS comprising 107 established single-nucleotide polymorphisms associated with colorectal cancer in European populations for 826 European-descent carriers of pathogenic variants in DNA mismatch repair genes (293 MLH1, 314 MSH2, 126 MSH6, 71 PMS2, and 22 EPCAM) from the Colon Cancer Family Registry, of whom 504 had colorectal cancer. There was no evidence of an association between the PRS and colorectal cancer risk, irrespective of which DNA mismatch repair gene was mutated, or sex (all 2-sided P >. 05). The hazard ratio per standard deviation of the PRS for colorectal cancer was 0.97 (95% confidence interval = 0.88 to 1.06; 2-sided P =. 51). Whereas PRSs are predictive of colorectal cancer in the general population, they do not predict Lynch syndrome colorectal cancer.

Original language	English (US)
Article number	pkab022
Journal	JNCI Cancer Spectrum
Volume	5
Issue number	2
DOIs	https://doi.org/10.1093/jncics/pkab022
State	Published - Apr 1 2021

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1093/jncics/pkab022

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Jenkins, M. A., Buchanan, D. D., Lai, J., Makalic, E., Dite, G. S., Win, A. K., Clendenning, M., Winship, I. M., Hayes, R. B., Huyghe, J. R., Peters, U., Gallinger, S., Marchand, L. L., Figueiredo, J. C., Pai, R. K., Newcomb, P. A., Church, J. M., Casey, G., & Hopper, J. L. (2021). Assessment of a Polygenic Risk Score for Colorectal Cancer to Predict Risk of Lynch Syndrome Colorectal Cancer. JNCI Cancer Spectrum, 5(2), Article pkab022. https://doi.org/10.1093/jncics/pkab022

Jenkins, MA, Buchanan, DD, Lai, J, Makalic, E, Dite, GS, Win, AK, Clendenning, M, Winship, IM, Hayes, RB, Huyghe, JR, Peters, U, Gallinger, S, Marchand, LL, Figueiredo, JC, Pai, RK, Newcomb, PA, Church, JM, Casey, G & Hopper, JL 2021, 'Assessment of a Polygenic Risk Score for Colorectal Cancer to Predict Risk of Lynch Syndrome Colorectal Cancer', JNCI Cancer Spectrum, vol. 5, no. 2, pkab022. https://doi.org/10.1093/jncics/pkab022

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title = "Assessment of a Polygenic Risk Score for Colorectal Cancer to Predict Risk of Lynch Syndrome Colorectal Cancer",

abstract = "It was not known whether the polygenic risk scores (PRSs) that predict colorectal cancer could predict colorectal cancer for people with inherited pathogenic variants in DNA mismatch repair genes - people with Lynch syndrome. We tested a PRS comprising 107 established single-nucleotide polymorphisms associated with colorectal cancer in European populations for 826 European-descent carriers of pathogenic variants in DNA mismatch repair genes (293 MLH1, 314 MSH2, 126 MSH6, 71 PMS2, and 22 EPCAM) from the Colon Cancer Family Registry, of whom 504 had colorectal cancer. There was no evidence of an association between the PRS and colorectal cancer risk, irrespective of which DNA mismatch repair gene was mutated, or sex (all 2-sided P >. 05). The hazard ratio per standard deviation of the PRS for colorectal cancer was 0.97 (95% confidence interval = 0.88 to 1.06; 2-sided P =. 51). Whereas PRSs are predictive of colorectal cancer in the general population, they do not predict Lynch syndrome colorectal cancer.",

author = "Jenkins, {Mark A.} and Buchanan, {Daniel D.} and John Lai and Enes Makalic and Dite, {Gillian S.} and Win, {Aung K.} and Mark Clendenning and Winship, {Ingrid M.} and Hayes, {Richard B.} and Huyghe, {Jeroen R.} and Ulrike Peters and Steven Gallinger and Marchand, {Lo{\"i}c Le} and Figueiredo, {Jane C.} and Pai, {Rish K.} and Newcomb, {Polly A.} and Church, {James M.} and Graham Casey and Hopper, {John L.}",

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doi = "10.1093/jncics/pkab022",

language = "English (US)",

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AU - Jenkins, Mark A.

AU - Buchanan, Daniel D.

AU - Lai, John

AU - Makalic, Enes

AU - Dite, Gillian S.

AU - Win, Aung K.

AU - Clendenning, Mark

AU - Winship, Ingrid M.

AU - Hayes, Richard B.

AU - Huyghe, Jeroen R.

AU - Peters, Ulrike

AU - Gallinger, Steven

AU - Marchand, Loïc Le

AU - Figueiredo, Jane C.

AU - Pai, Rish K.

AU - Newcomb, Polly A.

AU - Church, James M.

AU - Casey, Graham

AU - Hopper, John L.

PY - 2021/4/1

Y1 - 2021/4/1

N2 - It was not known whether the polygenic risk scores (PRSs) that predict colorectal cancer could predict colorectal cancer for people with inherited pathogenic variants in DNA mismatch repair genes - people with Lynch syndrome. We tested a PRS comprising 107 established single-nucleotide polymorphisms associated with colorectal cancer in European populations for 826 European-descent carriers of pathogenic variants in DNA mismatch repair genes (293 MLH1, 314 MSH2, 126 MSH6, 71 PMS2, and 22 EPCAM) from the Colon Cancer Family Registry, of whom 504 had colorectal cancer. There was no evidence of an association between the PRS and colorectal cancer risk, irrespective of which DNA mismatch repair gene was mutated, or sex (all 2-sided P >. 05). The hazard ratio per standard deviation of the PRS for colorectal cancer was 0.97 (95% confidence interval = 0.88 to 1.06; 2-sided P =. 51). Whereas PRSs are predictive of colorectal cancer in the general population, they do not predict Lynch syndrome colorectal cancer.

AB - It was not known whether the polygenic risk scores (PRSs) that predict colorectal cancer could predict colorectal cancer for people with inherited pathogenic variants in DNA mismatch repair genes - people with Lynch syndrome. We tested a PRS comprising 107 established single-nucleotide polymorphisms associated with colorectal cancer in European populations for 826 European-descent carriers of pathogenic variants in DNA mismatch repair genes (293 MLH1, 314 MSH2, 126 MSH6, 71 PMS2, and 22 EPCAM) from the Colon Cancer Family Registry, of whom 504 had colorectal cancer. There was no evidence of an association between the PRS and colorectal cancer risk, irrespective of which DNA mismatch repair gene was mutated, or sex (all 2-sided P >. 05). The hazard ratio per standard deviation of the PRS for colorectal cancer was 0.97 (95% confidence interval = 0.88 to 1.06; 2-sided P =. 51). Whereas PRSs are predictive of colorectal cancer in the general population, they do not predict Lynch syndrome colorectal cancer.

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Assessment of a Polygenic Risk Score for Colorectal Cancer to Predict Risk of Lynch Syndrome Colorectal Cancer

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