In patients receiving anthracyclines, NADPH oxidase polymorphism rs1883112 was strongly associated with cardiac fibrosis (OR 5.11; 95% CI 1.59-16.43).
Case-Control (n=97)
Do NADPH oxidase functional polymorphisms modulate the development of specific cardiac histological lesions induced by anthracycline treatment in cancer patients?
NADPH oxidase functional polymorphisms rs1883112 and rs4673 modulate the development of anthracycline-induced cardiac remodeling and fibrosis, providing a potential genetic basis for individual susceptibility to cardiotoxicity.
Effect estimate: OR 5.11 (95% CI 1.59-16.43)
OBJECTIVE: Treatment with anthracyclines may cause cardiac dysfunction, but the sequence of anthracycline-induced heart lesions has been incompletely characterized. NADPH oxidase, a key mediator of oxidative cardiac damage and remodeling, modulates anthracycline clinical cardiotoxicity. Our aim was to determine which cardiac histological lesions are specifically induced by anthracycline treatment and to investigate the role of NADPH functional genetic polymorphisms in their development. PATIENTS AND METHODS: Using a retrospective case-control design, we evaluated cardiac histological lesions and NADPH genotype (polymorphisms rs1883112, rs4673, and rs13058338) in 97 consecutive decedents with a cancer diagnosis (48 treated with anthracyclines). RESULTS: Myocytolysis (60%), patched myocardial necrosis (19%), and myocardial fibrosis (diffuse and patched; 62% and 23%, respectively) were associated with anthracycline treatment. In patients receiving anthracyclines, NADPH oxidase polymorphism rs4673 protected against focal myocardial necrosis (odds ratio OR, 0.11; 95% confidence interval CI, 0.20-0.63) whereas rs1883112 was strongly associated with cardiac fibrosis (OR, 5.11; 95% CI, 1.59-16.43), which was present in all homozygotes. CONCLUSION: Anthracyclines induce a cardiac remodeling pattern characterized by interstitial or patched fibrosis. The contribution of the functionally relevant NADPH polymorphisms rs1883112 and rs4673 to anthracycline-related heart lesions provides a plausible explanation for their modulation of cardiotoxicity. If confirmed, these findings may lead to better individualized strategies for early detection and prevention of anthracycline cardiotoxicity.
Cascales et al. (Mon,) conducted a case-control in Cancer (n=97). Anthracyclines vs. No anthracyclines was evaluated on Cardiac histological lesions (myocytolysis, myocardial necrosis, myocardial fibrosis) (OR 5.11, 95% CI 1.59-16.43). In patients receiving anthracyclines, NADPH oxidase polymorphism rs1883112 was strongly associated with cardiac fibrosis (OR 5.11; 95% CI 1.59-16.43).