What question did this study set out to answer?

This study aims to determine if genetic polymorphisms in carbonyl reductase genes affect the risk of anthracycline-related cardiomyopathy in childhood cancer survivors.

November 29, 2011Journal of Clinical OncologyOpen Access

Anthracycline-Related Cardiomyopathy After Childhood Cancer: Role of Polymorphisms in Carbonyl Reductase Genes—A Report From the Children's Oncology Group

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Why the study?

Do polymorphisms in carbonyl reductase genes (CBR1 and CBR3) modify the dose-dependent risk of anthracycline-related cardiomyopathy in childhood cancer survivors?

Key Points

This study aims to determine if genetic polymorphisms in carbonyl reductase genes affect the risk of anthracycline-related cardiomyopathy in childhood cancer survivors.
Compared 170 survivors with cardiomyopathy to 317 matched controls without cardiomyopathy using conditional logistic regression.
Analyzed impact of CBR1 and CBR3 genetic variants on cardiomyopathy risk associated with anthracycline exposure.
Evaluated dose-dependent association between anthracycline exposure and cardiomyopathy risk.
A dose-dependent increase in cardiomyopathy risk was noted with anthracycline exposure, with significant odds ratios ranging from 1.65 to 27.59 for various exposure levels (P(trend) < .001).
Individuals homozygous for the CBR3 G allele demonstrated a higher risk of cardiomyopathy at low to moderate anthracycline doses (OR, 5.48; P = .003).
High-dose anthracycline exposure consistently increased cardiomyopathy risk irrespective of genotype status.

Structured PICO

Do polymorphisms in carbonyl reductase genes (CBR1 and CBR3) modify the dose-dependent risk of anthracycline-related cardiomyopathy in childhood cancer survivors?

Population

487 childhood cancer survivors (170 cases with cardiomyopathy and 317 matched controls without cardiomyopathy, matched on cancer diagnosis, year of diagnosis, length of follow-up, and race/ethnicity)

Intervention

Anthracycline exposure (stratified by cumulative dose) and presence of CBR1 (1096G>A) and/or CBR3 (V244M) single nucleotide polymorphisms

Comparator

No anthracycline exposure or alternative CBR genotypes (CBR1:GA/AA and/or CBR3:GA/AA)

Outcome

Anthracycline-related cardiomyopathysafety

Homozygosity for the G allele in the CBR3 gene significantly increases the risk of anthracycline-related cardiomyopathy in childhood cancer survivors, even at low-to-moderate cumulative doses.

Discussion

No takes yet. Share an insight, caveat, or question.

Implication

May warrant closer cardiomyopathy surveillance in CBR3 GG carriers; leaves open prospective validation and risk-stratified dosing.

Cite This Study

Blanco et al. (2011) studied this question.

synapsesocial.com/papers/6a1004822badbc352aff2898 https://doi.org/10.1200/jco.2011.34.8987

Topics

Cardiomyopathy

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Anthracycline-Related Cardiomyopathy After Childhood Cancer: Role of Polymorphisms in Carbonyl Reductase Genes—A Report From the Children's Oncology Group

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Topics

Anthracycline-Related Cardiomyopathy After Childhood Cancer: Role of Polymorphisms in Carbonyl Reductase Genes—A Report From the Children's Oncology Group

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Also Consider

Topics

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