Prevalence of Factor V 1691 G–A (Leiden) and prothrombin G20210A polymorphisms and the risk of venous thrombosis among cancer patients (original) (raw)
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Prothrombotic genotypes and risk of venous thromboembolism in cancer
Thrombosis Research, 2018
Venous thromboembolism (VTE) is a common and potentially life-threatening complication in cancer. Patients with cancer are at a higher risk of VTE-related complications such as major bleeding during anticoagulant treatment, recurrence and mortality. Therefore, it is important to identify cancer patients with high risk of VTE in order to implement targeted prevention to those with a favorable benefit-to-harm ratio for thromboprophylaxis. VTE is strongly heritable, and during the last decades, several prothrombotic genotypes associated with VTE-risk have been identified. However, most of these studies were conducted in non-cancer patients, and the role of prothrombotic genotypes in cancer-related VTE is scarcely studied. In this review, we summarize current knowledge on the role of prothrombotic genotypes in cancer-related VTE, with particular focus on factor V Leiden, the prothrombin G20210A mutation and polymorphisms in the ABO gene. In general, many of the studies were small and performed in selected cancer populations, and they showed somewhat diverging results. Results from recent, larger, studies indicated that there is an association between these prothrombotic genotypes and cancer-related VTE. However, their predictive capability has not been assessed and the clinical implications are yet unclear. Future research should be conducted in larger cancer patient populations, and should be extended to include recently identified prothrombotic genotypes and assess the predictive value of genetic risk scores.
Medical Principles and Practice, 2012
Objective: To determine the risk of an association with some genetic polymorphisms involved in venous thromboembolism (VTE) gene variations (FVL, FV H1299R, FII G20210A, MTHFR C677T, MTHFR A1298C, PAI-1 4G/5G, β-fibrinogen -455 G → A, FXIII Val34Leu and GpIIIa HPA-1a) in cancer patients. Subjects and Methods: Among 78 cancer patients, 28 who had proven first episode of VTE were selected as the patient group, with 50 control samples selected from age-, sex- and body mass index-matched healthy volunteers (healthy group). The differences in frequency of genetic polymorphisms were found to be statistically insignificant between these two groups. Results: Logistic regression analysis after adjustment for age, sex, smoking and hypertension showed no difference. The screened mutations of these genes were not significantly associated with VTE risk. Conclusion: There is no possible benefit from genetic screening tests regarding VTE in cancer patients.
Experimental oncology
Factor VII (FVII) plays an important role in blood coagulation. The role of common polymorphisms influencing the FVII plasma levels in thromboembolic disorders has been evaluated but there is no published data related to the effect of FVII gene polymorphisms on the venous thrombosis risk in cancer. Aim: To investigate the association of three common functional polymorphisms in the promoter region of FVII gene: a decanucleotide insertion at position -323 (-323ins10-bp), a G to T substitution at position -401 (-401GT), and a G to A substitution at position -402 (-401GT) with venous thrombosis in cancer patients. Materials and Methods: The study included 60 cancer patients with venous thromboembolism (VTE) (group 1) and 130 cancer patients without VTE (group 2). Genotyping of -323ins10-bp, -401GT, and -402GA polymorphisms in the promoter region of FVII gene was performed by the method of single-strand conformation polymorphism analysis and sequencing. Factor V Leiden (FVL) was also determined in all cases. Results: The frequency of FVL was significantly greater in cancer patients with VTE compared with group 2 patients (p < 0.0001). For each polymorphism of FVII gene, the distributions of genotypes and allele frequencies were not significantly different between two groups of patients (p > 0.05). The results did not change significantly after the exclusion of patients carrying the FVL (p > 0.05). Conclusions: The screening for the -323ins10-bp, -401GT, and -402GA polymorphisms of FVII gene did not contribute to a meaningful diagnostic investigation in cancer patients with venous thrombosis.
British Journal of Haematology, 2000
We determined the prevalence of factor V Leiden and of prothrombin G20210A mutations in a cohort of unselected outpatients (n 748) referred for suspected deep vein thrombosis (DVT) and/or pulmonary embolism (PE) and a pooled analysis of similar studies was also performed. Based on the clinical presentation, the prevalence of factor V Leiden was 15´7% in the 83 patients with DVT and 14´1% in the 99 patients with PE compared with 5´3% in patients without DVT and/or PE (control group). The prevalence of the prothrombin G20210A mutation did not differ among the three groups (3´9% for controls, 4´8% for DVT and 3´9% for PE patients). We then divided the 99 patients with PE by separately analysing those with PE but without DVT (n 57) and those with PE and DVT (n 42). Compared with the control group, the prevalence of factor V Leiden was 10´5%, odds ratio (OR) 2´10 [95% confidence interval (95% CI) 0´68±5´45] in patients with primary PE and 19´1%, OR 4´20 (95% CI 1´54±10´30) in patients with DVT and PE. For the prothrombin G20210A mutation, no statistically significant differences were found between the control group and the three other groups. In conclusion, our data and the pooled analysis indicate that patients with primary PE are less often affected by the factor V Leiden mutation. No statistically significant differences were observed between patients and controls for the prothrombin G20210A mutation.
Characteristics and Risk Factors of Cancer Associated Venous Thromboembolism
Thrombosis research, 2015
The objective of this study was to examine the differences in commonly associated characteristics and risk factors of venous thromboembolism (VTE) between patients with and without cancer in a VTE population. Uniform data were collected for patients with a diagnosis of VTE obtaining care at CDC funded Thrombosis Network Centers. Patient characteristics and risk factors were compared in VTE patients with and without cancer. Logistic regression was used to calculate the unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) to assess patient characteristics and thrombotic risk factors more frequently identified among VTE patients with cancer compared to those without cancer. Between August 2003 and April 2011, 3,115 adult patients with a diagnosis of VTE including 189 (6.1%) patients with active cancer participated in the multi-site thrombosis registry. VTE patients with cancer had a higher prevalence of PE and DVT in unusual sites compared to those without cance...
Croatian medical journal, 2001
AIM To determine the prevalences of factor V Leiden and the G20210A mutation in the prothrombin gene (PT20210A) and the frequency of their association in healthy subjects and in patients with venous thromboembolism (VTE). METHOD We studied 160 Croatian patients with at least one episode of VTE and 155 healthy subjects as a control group. Genomic DNA was extracted according to standard procedures and the presence of factor V Leiden and PT20210A were determined by polymerase chain reaction-restriction fragment length polymorphism method. RESULTS The prevalences of factor V Leiden and PT20210A were in VTE patients 21% and 8% respectively, and 4% in controls for both mutations. Additionally, 4 patients were affected by double heterozygous defects, corresponding to a frequency of 3%, whereas none of the controls were double heterozygotes. The coexistence of the PT20210A in heterozygous carriers of factor V Leiden was 15% in VTE group. The results obtained for different subgroups of VTE p...
Canadian Medical Association Journal, 2013
G enome-wide association studies have reported that ABO blood type locus is an important genetic determinant of venous and arterial thrombosis, 1,2 leading to renewed interest in the association between ABO blood type and venous and arterial thrombosis. This challenges conventional thoughts on genetic screening for thrombophilia, which presently does not include ABO blood type. Individuals with an A or B blood type have an increased risk of venous thromboembolism and myocardial infarction compared with individuals with O blood type. 3-6 Earlier studies concluded that ABO antigen expression determines von Willebrand factor levels; 7-11 however, recent findings from genome-wide association studies suggest that ABO antigens may also exert their effect through other pathways. 12-16 Both factor V Leiden R506Q and prothrombin G20210A mutations have been consistently associated with increased risk of venous thrombosis but not consistently associated with the risk of arterial thrombosis. 17-19 In this study, we tested the hypothesis that ABO blood type, alone and in combination with the factor V Leiden R506Q and prothrombin G20210A mutations, is associated with the risk of venous thromboembolism and myocardial infarction in the general population.
European journal of haematology, 2016
The risk of thrombosis in individuals with rare compound thrombophilias, homozygous Factor V Leiden (FVL) plus heterozygous prothrombin G20210A (PTM), homozygous PTM plus heterozygous FVL, and homozygous FVL plus homozygous PTM is unknown. We identified, worldwide, individuals with these compound thrombophilias, predominantly through mailing members of the International Society on Thrombosis and Haemostasis. Physicians were sent a clinical questionnaire. Confirmatory copies of the genetic results were obtained. One hundred individuals were enrolled; 58% female. Seventy-one individuals had a venous thrombosis (includes superficial and deep vein thrombosis, and pulmonary embolism), 4 had an arterial thrombosis and 6 had both. Nineteen individuals had never had a thrombotic event. Thrombosis-free survival curves demonstrated that 50% of individuals had experienced a thrombotic event by 35 years of age, while 50% had a first venous thromboembolic event (VTE; includes all venous thrombos...