Open AccessAssociation of Anthracycline‐Related Cardiac Histological Lesions With NADPH Oxidase Functional Polymorphisms
Author(s) -
Cascales Almudena,
PastorQuirante Francisco,
SánchezVega Beatriz,
LuengoGil Ginés,
Corral Javier,
OrtuñoPacheco Guzmán,
Vicente Vicente,
Peña Francisco Ayala
Publication year - 2013
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1634/theoncologist.2012-0239
Subject(s) - medicine , anthracycline , nadph oxidase , pathology , oxidative stress , cancer , breast cancer
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.