Publication

Genome-wide association study of cardiovascular disease in testicular cancer patients treated with platinum-based chemotherapy

Steggink, L. C., Boer, H., Meijer, C., Lefrandt, J. D., Terstappen, L. W. M. M., Fehrmann, R. S. N. & Gietema, J. A., 3-Oct-2020, In : Pharmacogenomics journal. 13 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Steggink, L. C., Boer, H., Meijer, C., Lefrandt, J. D., Terstappen, L. W. M. M., Fehrmann, R. S. N., & Gietema, J. A. (2020). Genome-wide association study of cardiovascular disease in testicular cancer patients treated with platinum-based chemotherapy. Pharmacogenomics journal. https://doi.org/10.1038/s41397-020-00191-8

Author

Steggink, Lars C ; Boer, Hink ; Meijer, Coby ; Lefrandt, Joop D ; Terstappen, Leon W M M ; Fehrmann, Rudolf S N ; Gietema, Jourik A. / Genome-wide association study of cardiovascular disease in testicular cancer patients treated with platinum-based chemotherapy. In: Pharmacogenomics journal. 2020.

Harvard

Steggink, LC, Boer, H, Meijer, C, Lefrandt, JD, Terstappen, LWMM, Fehrmann, RSN & Gietema, JA 2020, 'Genome-wide association study of cardiovascular disease in testicular cancer patients treated with platinum-based chemotherapy', Pharmacogenomics journal. https://doi.org/10.1038/s41397-020-00191-8

Standard

Genome-wide association study of cardiovascular disease in testicular cancer patients treated with platinum-based chemotherapy. / Steggink, Lars C; Boer, Hink; Meijer, Coby; Lefrandt, Joop D; Terstappen, Leon W M M; Fehrmann, Rudolf S N; Gietema, Jourik A.

In: Pharmacogenomics journal, 03.10.2020.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Steggink LC, Boer H, Meijer C, Lefrandt JD, Terstappen LWMM, Fehrmann RSN et al. Genome-wide association study of cardiovascular disease in testicular cancer patients treated with platinum-based chemotherapy. Pharmacogenomics journal. 2020 Oct 3. https://doi.org/10.1038/s41397-020-00191-8


BibTeX

@article{1b8526d9ac7441eaa052c44e44259fce,
title = "Genome-wide association study of cardiovascular disease in testicular cancer patients treated with platinum-based chemotherapy",
abstract = "Genetic variation may mediate the increased risk of cardiovascular disease (CVD) in chemotherapy-treated testicular cancer (TC) patients compared to the general population. Involved single nucleotide polymorphisms (SNPs) might differ from known CVD-associated SNPs in the general population. We performed an explorative genome-wide association study (GWAS) in TC patients. TC patients treated with platinum-based chemotherapy between 1977 and 2011, age ≤55 years at diagnosis, and ≥3 years relapse-free follow-up were genotyped. Association between SNPs and CVD occurrence during treatment or follow-up was analyzed. Data-driven Expression Prioritized Integration for Complex Trait (DEPICT) provided insight into enriched gene sets, i.e., biological themes. During a median follow-up of 11 years (range 3-37), CVD occurred in 53 (14%) of 375 genotyped patients. Based on 179 SNPs associated at p ≤ 0.001, 141 independent genomic loci associated with CVD occurrence. Subsequent, DEPICT found ten biological themes, with the RAC2/RAC3 network (linked to endothelial activation) as the most prominent theme. Biology of this network was illustrated in a TC cohort (n = 60) by increased circulating endothelial cells during chemotherapy. In conclusion, the ten observed biological themes highlight possible pathways involved in CVD in chemotherapy-treated TC patients. Insight in the genetic susceptibility to CVD in TC patients can aid future intervention strategies.",
keywords = "LONG-TERM SURVIVORS, METABOLIC SYNDROME, CISPLATIN, EXPRESSION, NEPHROTOXICITY, ACTIVATION, BLEOMYCIN, APOPTOSIS, NECROSIS, INJURY",
author = "Steggink, {Lars C} and Hink Boer and Coby Meijer and Lefrandt, {Joop D} and Terstappen, {Leon W M M} and Fehrmann, {Rudolf S N} and Gietema, {Jourik A}",
year = "2020",
month = oct,
day = "3",
doi = "10.1038/s41397-020-00191-8",
language = "English",
journal = "Pharmacogenomics journal",
issn = "1470-269X",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - Genome-wide association study of cardiovascular disease in testicular cancer patients treated with platinum-based chemotherapy

AU - Steggink, Lars C

AU - Boer, Hink

AU - Meijer, Coby

AU - Lefrandt, Joop D

AU - Terstappen, Leon W M M

AU - Fehrmann, Rudolf S N

AU - Gietema, Jourik A

PY - 2020/10/3

Y1 - 2020/10/3

N2 - Genetic variation may mediate the increased risk of cardiovascular disease (CVD) in chemotherapy-treated testicular cancer (TC) patients compared to the general population. Involved single nucleotide polymorphisms (SNPs) might differ from known CVD-associated SNPs in the general population. We performed an explorative genome-wide association study (GWAS) in TC patients. TC patients treated with platinum-based chemotherapy between 1977 and 2011, age ≤55 years at diagnosis, and ≥3 years relapse-free follow-up were genotyped. Association between SNPs and CVD occurrence during treatment or follow-up was analyzed. Data-driven Expression Prioritized Integration for Complex Trait (DEPICT) provided insight into enriched gene sets, i.e., biological themes. During a median follow-up of 11 years (range 3-37), CVD occurred in 53 (14%) of 375 genotyped patients. Based on 179 SNPs associated at p ≤ 0.001, 141 independent genomic loci associated with CVD occurrence. Subsequent, DEPICT found ten biological themes, with the RAC2/RAC3 network (linked to endothelial activation) as the most prominent theme. Biology of this network was illustrated in a TC cohort (n = 60) by increased circulating endothelial cells during chemotherapy. In conclusion, the ten observed biological themes highlight possible pathways involved in CVD in chemotherapy-treated TC patients. Insight in the genetic susceptibility to CVD in TC patients can aid future intervention strategies.

AB - Genetic variation may mediate the increased risk of cardiovascular disease (CVD) in chemotherapy-treated testicular cancer (TC) patients compared to the general population. Involved single nucleotide polymorphisms (SNPs) might differ from known CVD-associated SNPs in the general population. We performed an explorative genome-wide association study (GWAS) in TC patients. TC patients treated with platinum-based chemotherapy between 1977 and 2011, age ≤55 years at diagnosis, and ≥3 years relapse-free follow-up were genotyped. Association between SNPs and CVD occurrence during treatment or follow-up was analyzed. Data-driven Expression Prioritized Integration for Complex Trait (DEPICT) provided insight into enriched gene sets, i.e., biological themes. During a median follow-up of 11 years (range 3-37), CVD occurred in 53 (14%) of 375 genotyped patients. Based on 179 SNPs associated at p ≤ 0.001, 141 independent genomic loci associated with CVD occurrence. Subsequent, DEPICT found ten biological themes, with the RAC2/RAC3 network (linked to endothelial activation) as the most prominent theme. Biology of this network was illustrated in a TC cohort (n = 60) by increased circulating endothelial cells during chemotherapy. In conclusion, the ten observed biological themes highlight possible pathways involved in CVD in chemotherapy-treated TC patients. Insight in the genetic susceptibility to CVD in TC patients can aid future intervention strategies.

KW - LONG-TERM SURVIVORS

KW - METABOLIC SYNDROME

KW - CISPLATIN

KW - EXPRESSION

KW - NEPHROTOXICITY

KW - ACTIVATION

KW - BLEOMYCIN

KW - APOPTOSIS

KW - NECROSIS

KW - INJURY

U2 - 10.1038/s41397-020-00191-8

DO - 10.1038/s41397-020-00191-8

M3 - Article

C2 - 33011741

JO - Pharmacogenomics journal

JF - Pharmacogenomics journal

SN - 1470-269X

ER -

ID: 135326871