Fibrinogen gamma gene rs2066865 and risk of cancer-related venous thromboembolism

Abstract

Methods VTE identification and validation All first lifetime events of VTE occurring among the participants in this period were identified using the hospital discharge diagnosis registry, the autopsy registry and the radiology procedure registry from University Hospital of North Norway (UNN), which is the sole provider of diagnostic radiology and treatment of VTE in the Tromsø area. Trained personnel adjudicated and recorded each VTE by extensive medical records review. The adjudication criteria for VTE were presence of signs and symptoms of PE or DVT combined with objective confirmation by radiological procedures, which resulted in treatment initiation (unless contraindications were specified). A VTE-event was classified as either a DVT or a PE. When a PE and DVT occurred concurrently, the event was classified as a PE. The identification and adjudication process of VTEs has been previously described in detail 1 .

Association of fibrinogen and plasmin inhibitor, but not coagulation factor XIII gene polymorphisms with coronary artery disease

“…Another SNP in the fibrinogen gene, but this one in the gamma-chain gene (rs2066865, 10034 C > T FGG), has been associated with venous thromboembolism and was also investigated in this CAD-study. LETS researchers found an association of the 10034C > T FGG polymorphism and increased risk of VTE (35), and the association was confirmed by several other studies (36)(37)(38)(39)(40)(41), even in the context of higher risk for VT among cancer patients with specific FGG genotypes (42). According to our results, this polymorphism is also associated with CAD.…”

Combined effects of five prothrombotic genotypes and cancer on the risk of a first venous thromboembolic event

“…Our findings on the role of individual prothrombotic genotypes and risk of cancer‐related VTE are in line with the previously published studies. Factor V Leiden, 23,24 ABO rs505922 and rs8176746, 25 ABO rs8176719, 26 prothrombin G20210A, 27‐30 and FGG rs2066865 41 have all been found to increase the risk of VTE in cancer patients. Moreover, SNPs in the F5 gene (FVL and rs4525) and FGG 41 have been shown to exert a more than additive effect on VTE risk when combined with cancer.…”

Prothrombotic genotypes and risk of venous thromboembolism in occult cancer

“…VTE has a strong hereditary component, and single nucleotide polymorphisms (SNPs) in genes encoding for factor V Leiden (FVL) [17,18], fibrinogen gamma (FGG) [19], factor 11 (F11) [20], prothrombin (F2) [21][22][23][24] and ABO blood group [25,26] are found to increase the VTE risk in cancer patients. Moreover, the combination of cancer and variations in the F5 (rs6025 and rs4524) and FGG (rs2066865) genes has been shown to increase the VTE risk on a supra-additive scale, indicating a biological interaction between the individual prothrombotic SNPs and active cancer [18,19]. Similarly, a genetic risk score (GRS) based on five prothrombotic SNPs was associated with VTE risk in overt cancer, and the combination of cancer and a high GRS (≥4 risk alleles) yielded a synergistic effect on VTE risk [27].…”