Study points to common SNP for stroke risk in cancer survivors

Researchers at St. Jude Children's Research Hospital (TN, USA) and the Hong Kong Chinese University (Hong Kong) have demonstrated that a common small nucleotide polymorphism (SNP) is badociated with an increased risk of stroke in children surviving from cancer treated with skull radiotherapy (TRC). The findings were presented at the AACR 2019 Annual Meeting (GA, USA, March 29 – April 3) and have implications for future intervention approaches.

Previous research has shown that the risk of stroke is increased sixfold among survivors treated with 30 to 50 Gy CRT compared to survivors who received none. Treatment with more than 50 Gy increases the risk by 11 times.

Yadav Sapkota, first author of the study, said: "The risk of stroke seems to vary in the same cathodic tube dose group even after taking into account other clinical and clinical factors. demographic. This tells us that there may be a genetic predisposition that influences the risk of stroke occurring in a survivor exposed to TRC. "

The team badyzed whole genome sequencing data from 686 survivors of childhood cancer of European origin who had been treated with CRT and were part of the SJLIFE study. 116 stroke developed.

The badysis revealed that exposure to the cathode ray tube combined with a common SSP on the 5p15.33 locus increased the risk by threefold compared to those without PNS. The dosage of the CRT was also important – the combination of the SNP with 25 to 50 Gy further increased the risk of stroke, up to five times more.

"We found that the common SNP had the most pronounced effect on the risk of stroke after an intermediate dose of radiation," noted Sapkota. "While survivors treated with more than 50 Gy of radiation still have an increased risk of stroke if they carry the SNP, we hypothesize that higher doses of radiation will replace radiation." Influence of genetics. "

The results were replicated in two independent groups of the SJLIFE study. One group included survivors of African descent and a survivor of European ancestry who did not undergo CRT. These results confirmed that the risk of developing a stroke is a combination of genetic treatments and CRT.

"TRC-treated survivors with this genetic variant can benefit from follow-up and counseling to minimize their modifiable cardiovascular risk factors," concluded Sapkota.

Validation in additional cohorts is now required, in addition to research on the mechanisms underlying the link between this SNP and the risk of stroke.