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FGG rs2066865 and the risk of cancer-related VTE
Figure 2. Cumulative incidence of venous thromboembolism in the pres- ence of FGG rs2066865 risk alleles during the active cancer period. VTE: venous thromboembolism; m: months.
Table 4. Measures of interaction between the homozygous fibrinogen gamma (FGG) variant and active cancer on venous thromboembolism.
FGG rs2066865
VTE
PE
DVT
Rothmans synergy index (RSI) (95% CI)
1.81 (1.02-3.21)
2.37 (1.05-5.39)
1.46 (0.65-3.27)
Relative excess risk by interaction (RERI) (95% CI)
9.6 (-2.4-21.6)
13.4 (-4.8-31.7)
6.3 (-9.6-22.1)
Proportion due to interaction (AP) (95% CI)
0.43 (0.11-0.74)
0.56 (0.21-0.90)
0.30 (-0.24-0.83)
Rothmans synergy index (RSI) >1 indicates a positive interaction or more than additivity; Relative excess risk by interaction (RERI) >0 indicates a positive interaction or more than additivity; Proportion due to interaction (AP) >0 indicates a positive interaction or more than additivity.VTE: venous thromboembolism; PE: pulmonary embolism; DVT: deep vein thrombosis; CI: confidence interval.
patients with two risk alleles at FGG rs2066865 developed VTE during the first six months after cancer diagnosis compared to 3.1% of cancer patients without risk alleles. Our findings suggest that FGG may be an attractive gene candidate to pursue in future research on prediction mod- els of VTE risk in cancer patients. We and others have pre- viously reported similar discriminative power of two vari- ants in the F5 gene (rs6025 and rs4524),23,24 and a genetic model including nine SNP reported promising predictive capacity on VTE risk in breast cancer.42 Recently, a new risk prediction model for cancer-related VTE, including clinical characteristics and genetic variants, reported a strong predictive capacity with an area under the curve (AUC) of 0.73 and performed better that the Khorana score (AUC 0.58).43
The main strengths of present study are the prospective design, high participation rate and long-term follow-up, making it possible to capture a large quantity of both inci- dent cancer- and VTE-events in the study population. Since all participants live within a single hospital catch- ment area, the probability of missing outcomes is low.
Moreover, both incident VTE-events and cancer diagnoses were systematically validated and objectively confirmed. The study was limited by the lack of statistical power in sub-group analysis (i.e. DVT/PE), illustrated by wide CI for our risk estimates. In addition, we did not have access to information on treatment regimens or medical compli- cations among cancer patients. Although there is no rea- son to believe that the type or intensity of treatment would be influenced by the genetic makeup, such data could have provided further insights into the possible interplay between genes and treatment-related risk fac- tors.
In conclusion, we found that homozygosity at FGG rs2066865 was associated with an increased risk of VTE, and yielded a synergistic effect on the VTE risk in combi- nation with active cancer, particularly on the risk of PE.
Funding
The K.G. Jebsen Thrombosis Research and Expertise Centre is supported by an independent grant from Stiftelsen Kristian Gerhard Jebsen.
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