Thrombogenesis-associated genetic determinants as predictors of thromboembolism and prognosis in cervical cancer

Abstract

Venous thromboembolism (VTE) is a leading cause of death among cancer patients. Khorana score (KS) is the most studied tool to predict cancer-related VTE, however, it exerts poor sensitivity. Several single-nucleotide polymorphisms (SNPs) have been associated with VTE risk in the general population, but whether they are predictors of cancer-related VTE is a matter of discussion. Compared to other solid tumours, little is known about VTE in the setting of cervical cancer (CC) and whether thrombogenesis-related polymorphisms could be valuable biomarkers in patients with this neoplasia. This study aims to analyse the effect of VTE occurrence on the prognosis of CC patients, explore the predictive capability of KS and the impact of thrombogenesis-related polymorphisms on CC-related VTE incidence and patients’ prognosis regardless of VTE. A profile of eight SNPs was evaluated. A retrospective hospital-based cohort study was conducted with 400 CC patients under chemoradiotherapy. SNP genotyping was carried on by using TaqMan® Allelic Discrimination methodology. Time to VTE occurrence and overall survival were the two measures of clinical outcome evaluated. The results indicated that VTE occurrence (8.5%) had a significant impact on the patient’s survival (log-rank test, P < 0.001). KS showed poor performance (KS ≥ 3, χ2, P = 0.191). PROCR rs10747514 and RGS7 rs2502448 were significantly associated with the risk of CC-related VTE development (P = 0.021 and P = 0.006, respectively) and represented valuable prognostic biomarkers regardless of VTE (P = 0.004 and P = 0.010, respectively). Thus, thrombogenesis-related genetic polymorphisms may constitute valuable biomarkers among CC patients allowing a more personalized clinical intervention.