title: Polymorphisms in genes related to oxidative stress (CAT, MnSOD, MPO, and eNOS) and acute toxicities from radiation therapy following lumpectomy for breast cancer.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Division of Cancer Prevention and Population Science, Department of Epidemiology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Ahn
authors.forename: Christine B
authors.initials: CB
authors.lastname: Ambrosone
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kanetsky
authors.forename: Chunqiao
authors.initials: C
authors.lastname: Tian
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Lehman
authors.forename: Silke
authors.initials: S
authors.lastname: Kropp
authors.forename: Irmgard
authors.initials: I
authors.lastname: Helmbold
authors.forename: Dietrich
authors.initials: D
authors.lastname: von Fournier
authors.forename: Wulf
authors.initials: W
authors.lastname: Haase
authors.forename: Marie Luise
authors.initials: ML
authors.lastname: Sautter-Bihl
authors.forename: Frederik
authors.initials: F
authors.lastname: Wenz
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000628:therapy; D002374:Catalase / Q000235:genetics*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005838:Genotype; D006801:Humans; D015412:Mastectomy, Segmental / Q000379:methods; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D018384:Oxidative Stress; D009195:Peroxidase / Q000235:genetics*; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011878:Radiotherapy / Q000009:adverse effects*; D012307:Risk Factors; D013482:Superoxide Dismutase / Q000235:genetics*
chemical_list: D002374:Catalase; D009195:Peroxidase; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase