From the Journals

Polygenic risk score may predict VTE in adolescents, but not adults, with ALL



Although patients with acute lymphoblastic leukemia (ALL) are at known risk of venous thromboembolism (VTE), there was no overall genetic correlation found to be associated with that susceptibility in the overall population. However, a significant genetic predisposition to VTE was found in adolescent ALL patients, according to a report published in Thrombosis Research.

The researchers assessed the prospectively registered VTE events and collected germline DNA in patients aged 1-45.9 years in the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 study, which took place from 2008 to 2016. The researchers performed polygenic risk score (PRS) analysis on VTE development in the NOPHO cohort, according to Kirsten Brunsvig Jarvis, MD, of Oslo University Hospital, and colleagues.

The researchers used summary statistics from two large genomewide association studies on VTE in adults (the International Network of Venous Thromboembolism Clinical Research Networks [INVENT] consortium and the UK Biobank).

Of 1,252 patients with ALL in the genetic cohort, 89 developed VTE (2.5-year cumulative incidence, 7.2%; 95% confidence interval,5.7-8.6) at a median 12.7 weeks from diagnosis.

Overall, an analysis of single-nucleotide polymorphisms (SNPs) from INVENT and UK Biobank studies did not reveal evidence of polygenic correlation with VTE in patients with ALL, the researchers reported. However, when separating adolescents aged 10.0-17.9 years (n = 231) from adults aged 18 years or older (n = 127), they saw polygenic overlap between the INVENT study and thromboembolism development in the adolescent population.

The best-fit polygenic risk score, including 16,144 SNPs, was associated with VTE in adolescents with ALL at a hazard ratio of 1.76 (95% CI, 1.23-2.52; P = .02).

Adolescent vs. adult risk

The researchers expressed surprise that they did not find evidence of genetic overlap in adults. But they stated that, in general, VTE occurs more frequently in adults as part of natural aging, while children and adolescents are physiologically protected. This might explain why genetics might play a stronger role in the high-risk situation of cancer and chemotherapy in adolescents who do not have as many additional exogenic risk factors as adults.

“The usefulness of genetic studies on [V]TE in the general adult population is limited when it comes to understanding the etiology of [V]TE in patients with ALL. However, we found evidence of polygenic overlap in subgroup analysis of adolescents aged 10.0-17.9 years with ALL, and we believe the genetics of [V]TE in this group should be further explored in future risk prediction models for identification of those who might benefit from thromboprophylaxis,” the researchers concluded.

The study was supported by research grant from the South-Eastern Norway Regional Health Authority. The authors reported that they had no conflicts of interest.

SOURCE: Jarvis KB et al. Thromb Res. 2020 Aug 11.doi: 10.1016/j.thromres.2020.08.015.

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