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Αλέξανδρος Γ. Σφακιανάκης

Monday, October 5, 2020

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

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

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

Pharmacogenomics J. 2020 Oct 03;:

Authors: Steggink LC, Boer H, Meijer C, Lefrandt JD, Terstappen LWMM, Fehrmann RSN, Gietema JA

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.



PMID: 33011741 [PubMed - as supplied by publisher]

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