This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ahn, J. Articles by Chang-Claude, J. Search for Related Content PubMed PubMed Citation Articles by Ahn, J. Articles by Chang-Claude, J.

Polymorphisms in Genes Related to Oxidative Stress (CAT, MnSOD, MPO, and eNOS) and Acute Toxicities from Radiation Therapy following Lumpectomy for Breast Cancer

Authors' Affiliations: ¹ Division of Cancer Prevention and Population Science, Department of Epidemiology, Roswell Park Cancer Institute, Buffalo, New York; ² Department of Biostatistics and Epidemiology and Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania; ³ BioServe Biotechnologies, Ltd., Laurel, Maryland; ⁴ Division of Clinical Epidemiology, German Cancer Research Center and ⁵ Department of Gynecological Radiology, Heidelberg University Hospital, Heidelberg, Germany; ⁶ Clinic for Radiotherapy and Radiooncology, St. Vincentius-Kliniken Karlsruhe and ⁷ Clinic for Radiotherapy, Karlsruhe Hospital GmbH, Karlsruhe, Germany; and ⁸ Department of Radiation Oncology, Universitätsklinikum Mannheim, Mannheim, Germany

Requests for reprints: Christine B. Ambrosone, Department of Epidemiology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263. Phone: 716-845-3082; Fax: 716-845-8487; E-mail: christine.ambrosone{at}roswellpark.org.

Purpose: Because radiotherapy exerts cytotoxic effects via generation of massive oxidative stress, we hypothesized that catalase, manganese superoxide dismutase, myeloperoxidase (MPO), and endothelial nitric oxide synthase (eNOS) genotypes might result in greater risk of radiotoxicity.

Experimental Design: Cases (n = 446) were Caucasian women with breast cancer who received radiotherapy following lumpectomy. Genotypes were determined by matrix-assisted laser desorption/ionization time-of-flight. The development of acute reactions (moist desquamation) associated with genotypes was modeled using the Cox proportional hazards model, accounting for cumulative biologically effective radiation dose.

Results: Genotypes associated with higher levels of reactive oxygen species (ROS) were not associated with risk of radiotoxicity. However, relationships between overweight/obesity [body mass index (BMI), >25] and radiotoxicity risk seemed to be modified by eNOS and MPO genotypes associated with higher generation of nitric oxide and ROS, respectively. Women with high BMI (>25) and eNOS GG genotypes were at more than a 6-fold increase in risk (hazard ratio, 6.39; 95% confidence interval, 2.53-16.15) compared with those with BMI <25, and for MPO, those with high BMI (>25) and GG genotypes also had greater risk of radiotoxicity (hazard ratio, 3.61; 95% confidence interval, 1.78-7.35) compared with those with BMI <25. Overweight/obesity was not a strong risk factor among women with other eNOS and MPO genotypes. Exploratory analysis using classification and regression trees indicated that total number of risk alleles contributed, in part, to acute toxicity outcomes among a subgroup of women.

Conclusions: Associations between BMI and radiotoxicity risk may be most apparent among women with genotypes related to higher levels of oxidative stress. Regression trees may be useful in future studies to examine the contributions of multiple factors to individual susceptibility to adverse effects of cancer treatment.

This article has been cited by other articles:

				R. A. Maki, V. A. Tyurin, R. C. Lyon, R. L. Hamilton, S. T. DeKosky, V. E. Kagan, and W. F. Reynolds Aberrant Expression of Myeloperoxidase in Astrocytes Promotes Phospholipid Oxidation and Memory Deficits in a Mouse Model of Alzheimer Disease J. Biol. Chem., January 30, 2009; 284(5): 3158 - 3169. [Abstract] [Full Text] [PDF]