Association between genetic mutations and risk of venous thromboembolism in patients with solid tumor malignancies: A systematic review and meta-analysis

Venous thromboembolism (VTE) is a frequent complication in cancer patients and is associated with significant morbidity, mortality, and burden on the health care system [1]. Previous studies have suggested an association between genetic mutations in solid tumors and VTE risk.MEDLINE and EMBASE databases were searched from inception to February 2021. We aimed to include studies presenting data on VTE and genetic mutations with >5% frequency in patients with melanoma, small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), and colon, gastric and ovarian cancers. Meta-analyses of proportions and size effects were conducted if possible.Of 682 eligible articles, we included 33 articles, of which 26 papers reporting on a total of 13,844 patients were included in the meta-analysis. The estimated proportions of VTE in lung cancer patients with EGFR, KRAS, and ALK mutations were 7.3, 18.2, and 30.6%, respectively, whereas for colon cancer with KRAS mutations was 13%. In NSCLC patients with EGFR, KRAS and ALK mutations the relative risk (RR) of VTE was 0.98 (0.81-1.18, P = 0.818), 1.24 (0.78-1.97 P = 0.358) and 1.70 (1.46-1.97, P < 0.001), respectively using a fixed-effects model. In patients with colon cancer and KRAS mutation, no significant increase in the VTE risk was observed according to the random-effects model, RR 1.31 (0.79-2.19, P = 0.285).In patients with NSCLC, the presence of ALK mutations was associated with a high proportion and RR of developing VTE. There was no significant increase in the risk of VTE in patients with colon cancer and KRAS mutations.