The association between two genetic polymorphisms in ITGB3 and increase risk of venous thromboembolism in cancer patients in Eastern Province of Saudi Arabia

Abstract

Venous thromboembolism (VTE) is one of the major complications in most cancer patients leading to poor prognosis and short survival. Several common clinical risk factors coexist in cancer patients are used as risk predictive biomarkers to help in the management and prevention of VTE. These include cancer site and stage, chemotherapy regimen and elevated biological markers. However, Genetic polymorphisms in genes controlling coagulation and fibrinolysis are significantly associated with VTE if detected, then they might be more sensitive individual predictive biomarkers for VTE risk assessment. This study was conducted to evaluate the association between ITGB3 rs3809865 and rs5918 with VTE risk as well as monitor the effect of VTE on overall survival of these cancer patients. In this retrospective case-control study, 195 cancer patients' formalin-fixed paraffin embedded tissue (FFPE) samples were collected (controls n = 157, case n = 38) using the stored data through Jan 2010 to Sep 2018 from King Fahad Specialist Hospital in Dammam. Samples were genotyped using TaqMan genotyping assay, then logistic regression analysis and Chi-square were used to predict the association between risk factors and VTE. Survival Comparison was tested by the log-rank test. Genetic polymorphisms in ITGB3 (rs3809865 and rs5918) found not to be associated with VTE increasing risk in cancer patients (p>0.05). While the advanced stage was potentially increasing the risk of VTE events (OR 5.1 CI 2.01-12.9p = 0.001). Patients with VTE showed a poor overall survival reflected by the median survival rate of only three years compared to seven years for cancer patients without VTE. This study highlighted the potential influence of VTE on prognosis and survival of cancer patients and raised the importance of exploring risk predictive biomarkers in our population. This will improve the risk prediction biomarkers leading to implementing safe and effective thrombosis prophylaxis strategies.

Keywords: Cancer; Eastern Province; Genetic Polymorphisms; ITGB3 gene; Risk; Saudi Arabia; Venous Thromboembolism.

Fig. 1

Representative of direct sequence electropherogram of the gene region, ITGB3. Arrow indicates the position of rs3809865. (A) Sequence with genotype AA of rs3809865. (B) Sequence with genotype TT of rs3809865. A clear peak in electropherogram indicates a homozygous result.

Fig. 2

Kaplan Meier survival curve. Kaplan Meier survival comparison between cases and controls shows clear difference in survival probabilities. Log Rank survival analysis revealed a statistically significant difference between cases and control survival with a p-value < 0.001.