Factor V Leiden, Prothrombin G20210A, and MTHFR C677T Polymorphisms in Cancer Patients with Venous Thromboembolism

Abstract

Intro/Aims: Venous thromboembolism (VTE) is a common complication in cancer patients. The role of thrombophilic polymorphisms in cancer related VTE remains poorly explored. Aim 1 of this study was to determine if Factor V Leiden (G1691A), Prothrombin (PT) G20210A or methylenetetrahydrofolate reductase (MTHFR) C677T are associated with the increased occurrence of VTE in adult oncology subjects compared to nononcology subjects. Aim 2 of this study was to determine if cancer patients with the MTHFR C677T polymorphism who are treated with antimetabolite therapy have an increased incidence of VTE compared to cancer patients who are treated with other chemotherapy.Setting/Methods: A descriptive, comparative, retrospective chart analysis was utilized for this study in an outpatient hematology, oncology clinic in Southern Arizona. Enrolled were 100 adult subjects (age 18 - 85) with documented history of VTE (27 subjects with cancer and 73 noncancer). Subjects were evaluated for Factor V Leiden, PT G20210A, and MTHFR C677T prior to the study. Eleven subjects were treated with antimetabolite chemotherapy and 8 subjects were treated with other chemotherapy.Results: The overall polymorphism frequency for Factor V Leiden was 21%, PT G20210A 4%, and MTHFR C677T 50%. Factor V Leiden was found in 11.1% of cancer subjects and 24.7% of noncancer subjects. Prothrombin G20210A was found in 3.7% of cancer subjects and 4.1% of noncancer subjects. MTHFR C677T was present in 25.9% of cancer subjects and 58.9% of noncancer subjects. No statistical significance was observed between subjects treated with an antimetabolite and positive for MTHFR C677T compared with those treated with other types of chemotherapy.Conclusion: Analysis of the data collected in this study demonstrated overall higher rates than the expected frequencies of all polymorphism for both the cancer and noncancer patients with documented VTE. In this small retrospective study, the only significant finding was that the MTHFR C677T polymorphism was more prevalent in the noncancer group.Currently, there are no specific guidelines for VTE prevention in the outpatient oncology setting. Identification of risk factors, including prothrombotic mutations may reduce risk of VTE and provide guidance for prophylactic treatment recommendations in the outpatient setting.