6 mutations are associated with increased risk of blood clots in cancer patients

This article comes from NEJM Journal Watch Mutational Profiling and Cancer-Associated Thrombosis Mutational Profiling and Cancer-Associated Thrombosis Commentary Author: Brady L.
Stein, MD, MHS 6 mutations are associated with an increased risk of cancer-associated thrombosis and are not Affected by the type of cancer.

The causes of cancer-related thrombosis (CAT) are multifaceted, and are affected by factors such as cancer staging, chemotherapy, postoperative conditions/lack of exercise, history of thrombosis, and whether vascular access is established.

The Khorana score combines cancer type, blood count before chemotherapy (including the use of erythropoietin stimulants), and body mass index to design a risk score; however, we still hope to be able to more accurately identify high-risk patients.

The researchers summarized a large database containing more than 14,000 tumor samples (11,695 patients), with the purpose of exploring the relationship between tumor molecular profiles and CAT.

Important results include: a total of 693 CATs occurred, with pancreatic cancer patients with the highest event rate.

The clinical risk factors for CAT include cytotoxic chemotherapy (hazard ratio, 1.
63), history of venous thromboembolism (hazard ratio, 2.
2) and metastatic disease (hazard ratio, 2.
6).

Regardless of the tumor type, KRAS (hazard ratio, 1.
34), STK11 (hazard ratio, 2.
12), KEAP1 (HR, 1.
84), CTNNB1 (HR, 1.
73), CDKN2B (hazard ratio, 1.
45) and MET (hazard ratio, 1.
83) The mutations are all related to CAT.

Researchers found that 30% of patients have clonal hematopoietic mutations, but surprisingly, these mutations (including JAK2 V617F) are not related to CAT.

Comment on this novel study to deepen our understanding of CAT risk factors.

Six mutations are independently associated with an increased risk of thrombosis in patients with solid tumors (most of whom have metastatic disease).

We need to conduct more studies to determine the mechanism by which these mutations promote the pathophysiology of CAT; researchers believe that the STK11 mutation may be related to the increased production of tumor granulocyte colony stimulating factor (G-CSF) and the formation of extracellular trapping nets of neutrophils.

In patients with myeloproliferative tumors and in other studies conducted on JAK2 V617F clonal hematopoietic patients, JAK2 V617F can significantly increase the risk of thrombosis; this study showed that the mutation did not increase the risk of thrombosis, which was unexpected.

The author acknowledges the limitations of retrospective research and the need for further verification.

But in the future, CAT predictions can certainly incorporate the sequencing information of tumor mutations.

The reviewed article Dunbar A et al.
Genomic profiling identifies somatic mutations predicting thromboembolic risk in patients with solid tumors.
Blood 2021 Apr 15; 137:2103.
(https://doi.
org/10.
1182/blood.
2020007488) NEJM journals collection NEJM The NEJM Journal Watch is published by the NEJM Group.
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