Polygenic risk score as a determinant of risk of non-melanoma skin cancer in a European-descent renal transplant cohort

Caragh P Stapleton; Kelly A Birdwell; Amy Jayne McKnight; Alexander P Maxwell; Patrick B Mark; M Lee Sanders; Fiona A Chapman; Jessica van Setten; Paul J Phelan; Claire Kennedy; Alan Jardine; Jamie P Traynor; Brendan Keating; Peter J Conlon; Gianpiero L Cavalleri

doi:10.1111/ajt.15057

Polygenic risk score as a determinant of risk of non-melanoma skin cancer in a European-descent renal transplant cohort

Caragh P Stapleton, Kelly A Birdwell, Amy Jayne McKnight, Alexander P Maxwell, Patrick B Mark, M Lee Sanders, Fiona A Chapman, Jessica van Setten, Paul J Phelan, Claire Kennedy, Alan Jardine, Jamie P Traynor, Brendan Keating, Peter J Conlon, Gianpiero L Cavalleri

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Abstract

Renal transplant recipients have an increased risk of non-melanoma skin cancer (NMSC) compared to in the general population. Here, we show polygenic risk scores (PRS) calculated from genome-wide association studies (GWAS) of NMSC in a general, nontransplant setting, can predict risk of, and time to posttransplant skin cancer. Genetic variants, reaching predefined P-value thresholds were chosen from published squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) nontransplant GWAS. Using these GWAS, BCC and SCC PRS were calculated for each sample across three European ancestry renal transplant cohorts (n = 889) and tested as predictors of case:control status and time to NMSC posttransplant. BCC PRS calculated at P-value threshold 1 × 10 ⁻⁵ was the most significant predictor of case:control status of NMSC posttransplant (OR = 1.61; adjusted P =.0022; AUC [full model adjusted for clinical predictors and PRS] = 0.81). SCC PRS at P-value threshold 1 × 10 ⁻⁵ was the most significant predictor of time to posttransplant NMSC (adjusted P = 9.39 × 10 ⁻⁷; HR = 1.41, concordance [full model] = 0.74). PRS of nontransplant NMSC is predictive of case:control status and time to NMSC posttransplant. These results are relevant to how genomics can risk stratify patients to help develop personalized treatment regimens.

Original language	English
Pages (from-to)	801-810
Journal	American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
Volume	19
Issue number	3
Early online date	07 Aug 2018
DOIs	https://doi.org/10.1111/ajt.15057
Publication status	Published - 01 Mar 2019

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Polygenic risk score as a determinant of risk of non-melanoma skin cancer in a European-descent renal transplant cohort
© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons. This work is made available online in accordance with the publisher’s policies. Please refer to any applicable terms of use of the publisher.
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Projects

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R3789CPH: Discovery of an integrated risk profile for chronic kidney disease and development of a clinical biomarker panel for personalising medicine (Stratified medicine for chronic kidney disease)

McKnight, A. J. & Maxwell, P.

15/06/2016 → …

Project: Research

Cite this

Stapleton, C. P., Birdwell, K. A., McKnight, A. J., Maxwell, A. P., Mark, P. B., Sanders, M. L., Chapman, F. A., van Setten, J., Phelan, P. J., Kennedy, C., Jardine, A., Traynor, J. P., Keating, B., Conlon, P. J., & Cavalleri, G. L. (2019). Polygenic risk score as a determinant of risk of non-melanoma skin cancer in a European-descent renal transplant cohort. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 19(3), 801-810. https://doi.org/10.1111/ajt.15057

Stapleton, Caragh P ; Birdwell, Kelly A ; McKnight, Amy Jayne ; Maxwell, Alexander P ; Mark, Patrick B ; Sanders, M Lee ; Chapman, Fiona A ; van Setten, Jessica ; Phelan, Paul J ; Kennedy, Claire ; Jardine, Alan ; Traynor, Jamie P ; Keating, Brendan ; Conlon, Peter J ; Cavalleri, Gianpiero L. / Polygenic risk score as a determinant of risk of non-melanoma skin cancer in a European-descent renal transplant cohort. In: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2019 ; Vol. 19, No. 3. pp. 801-810.

@article{f96e2fbc246641a4bd48f650c922d660,

title = "Polygenic risk score as a determinant of risk of non-melanoma skin cancer in a European-descent renal transplant cohort",

abstract = "Renal transplant recipients have an increased risk of non-melanoma skin cancer (NMSC) compared to in the general population. Here, we show polygenic risk scores (PRS) calculated from genome-wide association studies (GWAS) of NMSC in a general, nontransplant setting, can predict risk of, and time to posttransplant skin cancer. Genetic variants, reaching predefined P-value thresholds were chosen from published squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) nontransplant GWAS. Using these GWAS, BCC and SCC PRS were calculated for each sample across three European ancestry renal transplant cohorts (n = 889) and tested as predictors of case:control status and time to NMSC posttransplant. BCC PRS calculated at P-value threshold 1 × 10 −5 was the most significant predictor of case:control status of NMSC posttransplant (OR = 1.61; adjusted P =.0022; AUC [full model adjusted for clinical predictors and PRS] = 0.81). SCC PRS at P-value threshold 1 × 10 −5 was the most significant predictor of time to posttransplant NMSC (adjusted P = 9.39 × 10 −7; HR = 1.41, concordance [full model] = 0.74). PRS of nontransplant NMSC is predictive of case:control status and time to NMSC posttransplant. These results are relevant to how genomics can risk stratify patients to help develop personalized treatment regimens. ",

author = "Stapleton, {Caragh P} and Birdwell, {Kelly A} and McKnight, {Amy Jayne} and Maxwell, {Alexander P} and Mark, {Patrick B} and Sanders, {M Lee} and Chapman, {Fiona A} and {van Setten}, Jessica and Phelan, {Paul J} and Claire Kennedy and Alan Jardine and Traynor, {Jamie P} and Brendan Keating and Conlon, {Peter J} and Cavalleri, {Gianpiero L}",

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Stapleton, CP, Birdwell, KA, McKnight, AJ , Maxwell, AP, Mark, PB, Sanders, ML, Chapman, FA, van Setten, J, Phelan, PJ, Kennedy, C, Jardine, A, Traynor, JP, Keating, B, Conlon, PJ & Cavalleri, GL 2019, 'Polygenic risk score as a determinant of risk of non-melanoma skin cancer in a European-descent renal transplant cohort', American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, vol. 19, no. 3, pp. 801-810. https://doi.org/10.1111/ajt.15057

Polygenic risk score as a determinant of risk of non-melanoma skin cancer in a European-descent renal transplant cohort. / Stapleton, Caragh P; Birdwell, Kelly A; McKnight, Amy Jayne ; Maxwell, Alexander P; Mark, Patrick B; Sanders, M Lee; Chapman, Fiona A; van Setten, Jessica; Phelan, Paul J; Kennedy, Claire; Jardine, Alan; Traynor, Jamie P; Keating, Brendan; Conlon, Peter J; Cavalleri, Gianpiero L.

In: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, Vol. 19, No. 3, 01.03.2019, p. 801-810.

Research output: Contribution to journal › Article

TY - JOUR

T1 - Polygenic risk score as a determinant of risk of non-melanoma skin cancer in a European-descent renal transplant cohort

AU - Stapleton, Caragh P

AU - Birdwell, Kelly A

AU - McKnight, Amy Jayne

AU - Maxwell, Alexander P

AU - Mark, Patrick B

AU - Sanders, M Lee

AU - Chapman, Fiona A

AU - van Setten, Jessica

AU - Phelan, Paul J

AU - Kennedy, Claire

AU - Jardine, Alan

AU - Traynor, Jamie P

AU - Keating, Brendan

AU - Conlon, Peter J

AU - Cavalleri, Gianpiero L

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Renal transplant recipients have an increased risk of non-melanoma skin cancer (NMSC) compared to in the general population. Here, we show polygenic risk scores (PRS) calculated from genome-wide association studies (GWAS) of NMSC in a general, nontransplant setting, can predict risk of, and time to posttransplant skin cancer. Genetic variants, reaching predefined P-value thresholds were chosen from published squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) nontransplant GWAS. Using these GWAS, BCC and SCC PRS were calculated for each sample across three European ancestry renal transplant cohorts (n = 889) and tested as predictors of case:control status and time to NMSC posttransplant. BCC PRS calculated at P-value threshold 1 × 10 −5 was the most significant predictor of case:control status of NMSC posttransplant (OR = 1.61; adjusted P =.0022; AUC [full model adjusted for clinical predictors and PRS] = 0.81). SCC PRS at P-value threshold 1 × 10 −5 was the most significant predictor of time to posttransplant NMSC (adjusted P = 9.39 × 10 −7; HR = 1.41, concordance [full model] = 0.74). PRS of nontransplant NMSC is predictive of case:control status and time to NMSC posttransplant. These results are relevant to how genomics can risk stratify patients to help develop personalized treatment regimens.

AB - Renal transplant recipients have an increased risk of non-melanoma skin cancer (NMSC) compared to in the general population. Here, we show polygenic risk scores (PRS) calculated from genome-wide association studies (GWAS) of NMSC in a general, nontransplant setting, can predict risk of, and time to posttransplant skin cancer. Genetic variants, reaching predefined P-value thresholds were chosen from published squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) nontransplant GWAS. Using these GWAS, BCC and SCC PRS were calculated for each sample across three European ancestry renal transplant cohorts (n = 889) and tested as predictors of case:control status and time to NMSC posttransplant. BCC PRS calculated at P-value threshold 1 × 10 −5 was the most significant predictor of case:control status of NMSC posttransplant (OR = 1.61; adjusted P =.0022; AUC [full model adjusted for clinical predictors and PRS] = 0.81). SCC PRS at P-value threshold 1 × 10 −5 was the most significant predictor of time to posttransplant NMSC (adjusted P = 9.39 × 10 −7; HR = 1.41, concordance [full model] = 0.74). PRS of nontransplant NMSC is predictive of case:control status and time to NMSC posttransplant. These results are relevant to how genomics can risk stratify patients to help develop personalized treatment regimens.

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DO - 10.1111/ajt.15057

M3 - Article

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SP - 801

EP - 810

JO - American Journal of Transplantation

JF - American Journal of Transplantation

SN - 1600-6135

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Stapleton CP, Birdwell KA, McKnight AJ , Maxwell AP, Mark PB, Sanders ML et al. Polygenic risk score as a determinant of risk of non-melanoma skin cancer in a European-descent renal transplant cohort. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2019 Mar 1;19(3):801-810. https://doi.org/10.1111/ajt.15057