Abstract
Late stage epithelial ovarian cancer has a dismal prognosis. Identification of pharmacogenomic markers (i.e. polymorphisms) to stratify patients to optimize individual therapy is of paramount importance. We here report the retrospective analysis of polymorphisms in 5 genes (ATM, ATR, Chk1, Chk2 and CDK12) involved in the cellular response to platinum in a cohort of 240 cancer patients with late stage ovarian cancer. The aim of the present study was to evaluate associations between the above mentioned SNPs and patients’ clinical outcomes: overall survival (OS) and progression free survival (PFS). None of the ATM, ATR, Chk1 and Chk2 polymorphisms was found to significantly affect OS nor PFS in this cohort of patients. Genotype G/G of CDK12 polymorphism (rs1054488) predicted worse OS and PFS than the genotype A/A-A/G in univariate analysis. The predictive value was lost in the multivariate analysis. The positive correlation observed between this polymorphism and age, grade and residual tumor may explain why the CDK12 variant was not confirmed as an independent prognostic factor in multivariate analysis.The importance of CDK12 polymorphism as possible prognostic biomarker need to be confirmed in larger ovarian cancer cohorts, and possibly in other cancer population responsive to platinum agents.
Highlights
Encoded protein, predisposing subjects to disease and/or possibly influencing their response to a given drug, both in terms of activity and toxicity[11]
DNA damages are repaired by defined DNA repair pathways; there are common sensor proteins that are activated by the presence of the damage and that coordinate the cellular response with the final aim to block cell cycle progression to allow repair, if the damage is reparable, and /or activate cell death, if the damage is too severe to be repaired[23,24]
This study investigated the association of genomic variations in five different genes and outcomes in advanced stage ovarian cancer patients receiving chemotherapy
Summary
Encoded protein, predisposing subjects to disease and/or possibly influencing their response to a given drug, both in terms of activity and toxicity[11]. In this post genomic era, the possibility of individualizing cancer therapy by using molecular markers (SNPs) that predict the toxicity of chemotherapy has been pursued with some success[12,13,14]. More controversial are the results of SNPs in predicting the efficacy of anticancer agents[15,16,17]. The aim of the present study was to evaluate associations between the above mentioned SNPs and patients’clinical outcome, overall survival (OS) and progression free survival (PFS)
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