Genetic Variant Boosts Stroke Risk in Childhood Cancer Survivors

by Colleen Fleiss on  April 4, 2019 at 8:23 AM Cancer News
RSS Email Print This Page Comment bookmark
Font : A-A+

In childhood cancer survivors who received cranial radiation therapy (CRT) a common single nucleotide polymorphism (SNP) was linked to an increased risk for developing stroke, according to results presented at the AACR Annual Meeting 2019, March 29-April 3.
Genetic Variant Boosts Stroke Risk in Childhood Cancer Survivors
Genetic Variant Boosts Stroke Risk in Childhood Cancer Survivors

"We have identified a genetic risk factor that confers a high risk of stroke among childhood cancer survivors treated with cranial radiation therapy," said Yadav Sapkota, PhD, clinical research scientist at St. Jude Children's Research Hospital. "Our findings can help better identify survivors who are at the highest risk for developing stroke and formulate intervention strategies to minimize their risk," he said.

Compared to survivors who do not receive CRT, those who receive between 30 and 50 Gray (Gy) have a six-fold risk for developing stroke, while those who receive more than 50 Gy have an 11-fold risk for developing stroke, according to past studies, he added. "However, the stroke risk seems to vary within the same CRT dose group, even after accounting for other clinical and demographic factors," Sapkota noted. "This indicated to us that there may be genetic predisposition that influences a CRT-exposed survivor's risk for developing stroke," he said.

To identify common SNPs (defined here as occurring in greater than 5 percent of the study population) associated with stroke risk, Sapkota and colleagues analyzed whole-genome sequencing data from 686 childhood cancer survivors treated with CRT for their primary cancer from the St. Jude Lifetime Cohort (SJLIFE) study; all survivors in this analysis were of European descent. Of these survivors, 116 (17 percent) developed clinically diagnosed stroke.

Following multivariable analysis, the authors found that CRT-exposed survivors harboring a common SNP on the 5p15.33 locus were nearly three times as likely to develop a stroke compared to CRT-exposed survivors without the SNP. The dose of radiation appeared to affect the SNP-risk association; survivors treated with 25-50 Gy had nearly five times the risk of developing stroke if they carried the SNP, while patients treated with less than 25 Gy or more than 50 Gy had roughly three times the risk of developing stroke if they carried the SNP.

"We found that the common SNP had the most pronounced effect on the risk for stroke following an intermediate dose of radiation," noted Sapkota. "While survivors treated with greater than 50 Gy of radiation still have an increased risk of stroke if they carry the SNP, we hypothesize that higher doses of radiation displace the influence of genetics," he said.

The researchers replicated the finding in two independent groups of survivors from the SJLIFE study, consisting of survivors of African ancestry who received CRT and survivors of European descent who did not receive CRT. "Results of the replication analysis suggest that a combination of CRT treatment and genetic factors can greatly increase childhood cancer survivors' risk for developing stroke," said Sapkota. "Survivors treated with CRT who carry this genetic variant can benefit from being monitored and counseled to minimize their modifiable cardiovascular risk factors," he added.

A limitation of the study is the small sample size, which will require validation in additional cohorts, Sapkota said. Functional experiments are also needed to gain mechanistic insights underlying the link between the common SNP and risk of stroke among survivors treated with CRT - thereby informing potential intervention-based approaches.

Source: Eurekalert

Post a Comment

Comments should be on the topic and should not be abusive. The editorial team reserves the right to review and moderate the comments posted on the site.
Notify me when reply is posted
I agree to the terms and conditions
Advertisement

Recommended Reading

More News on:

Cancer and Homeopathy Bellīs Palsy Genetics and Stem Cells Diet Lifestyle and Heart Disease Acute Lymphoblastic Leukemia Mitral Valve Stenosis And Mitral Valve Replacement Congenital Heart Disease Stress and the Gender Divide Cancer Facts Stroke Facts 

News A - Z

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

News Search

Medindia Newsletters

Subscribe to our Free Newsletters!

Terms & Conditions and Privacy Policy.

Find a Doctor

Stay Connected

  • Available on the Android Market
  • Available on the App Store

News Category

News Archive