Impact of thrombophilic genes mutations on thrombosis risk in Egyptian nonmetastatic cancer patients

Abstract

Venous thromboembolism (VTE) is a common complication in cancer patients. Several genetic risk factors related to thrombophilia are known; however, their contributions to thrombotic tendency in cancer patients have conflicting results. We aimed to determine the prevalence of factor V Leiden (FVL), prothrombin (PTH) G20210A and methylene tetrahydrofolate reductase (MTHFR) C677T gene polymorphisms in Egyptian nonmetastatic cancer patients and their influence on thrombosis risk in those patients. Factor V Leiden, PTH G20210A and MTHFR C677T polymorphisms were detected in 40 cancer patients with VTE (group 1) and 40 cancer patients with no evidence of VTE (group 2) by PCR-based DNA analysis. Factor V and MTHFR mutations were higher in group 1 than in group 2 (factor V heterozygous mutation: 20 vs. 7.5%, homozygous mutation: 10 vs. 2.5%; MTHFR heterozygous mutation: 40 vs. 25%, homozygous mutation 5 vs. 0%, respectively) (P = 0.03). Mortality rate was higher in group 1 (75%) than in group 2 (25%; P < 0.001). No difference was found between those groups regarding PTH mutation (P = 1). Mortality rate was higher in the presence of homozygous and heterozygous factor V mutation (100 and 82%, respectively) compared to the wild type (41%) (P = 0.0006). Having any of the three studied gene mutations worsened the overall survival (P = 0.0003). Cox regression proved that both thrombosis and presence of factor V mutation are independent factors affecting survival in cancer patients (P < 0.001 and P = 0.01, respectively). In conclusion, there is an association between factor V and MTHFR mutations and risk of VTE in Egyptian cancer patients. Thrombosis and presence of factor V mutation are independent factors that influence survival in those patients.

Inherited thrombophilia gene mutations and risk of venous thromboembolism in patients with cancer: A systematic review and meta‐analysis

“…In the remaining genes or mutations, we found that heterozygous and homozygous MTHFR C677T 13,25,32,48,52 were associated with pooled ORs for VTE of 1.50 (95% CI: 1.00-2.24) and 1.38 (95% CI: 0.87-2.22), respectively, but only a heterozygous mutation was borderline significant (Table 1). Among those with heterozygous and homozygous PAI-1 4G/5G, 25,37,48,52 VEGFA C634G, 29,46 and VEGF C2578A, 29,36 no significant increase in the odds of VTE was found, but moderate to considerable heterogeneity was observed (Table 1).…”

“…In the 18 and 13 studies evaluating FVL [10][11][12][13]26,28,31,32,37,39,[41][42][43][44][45]47,48,52 and Prothrombin Factor II G20210 [11][12][13]26,31,32,37,39,41,42,47,48,52 gene mutations, respectively, the overall odds of VTE were 2.28 (95% CI:…”

“…A total of 4274 studies were screened for eligibility, of which 3433 and 814 were excluded after title and abstract screening and full‐text screening, respectively (Figure 1). Eventually, 37 studies 10–13,25–57 (27 studies identified via search strategy and 10 studies identified via reference list searching) involving different cancer types and treatments were included in the systematic review, of which 28 studies 10–13,25–29,31,32,36,37,39,41–52,54,56 were included in the meta‐analysis (Table S1). Key study characteristics and estimates are shown in Tables S2 and S3.…”

“…In the 18 and 13 studies evaluating FVL 10–13,26,28,31,32,37,39,41–45,47,48,52 and Prothrombin Factor II G20210 11–13,26,31,32,37,39,41,42,47,48,52 gene mutations, respectively, the overall odds of VTE were 2.28 (95% CI: 1.51–3.48, I 2 = 52%) and 2.14 (95% CI: 1.14–4.03, I 2 = 20%) in those with a gene mutation (Table 1). The pooled odds of VTE were increased in the post‐surgical and mixed treatment settings for both mutations, although only statistically significant in the mixed treatment setting (Figure 3).…”