( 6) reported previously that, in this study population, overweight/obesity and alcohol consumption were associated with an increased risk of acute radiotoxicity. Patient-related factors include breast size, smoking habits, axillary lymph drainage before treatment, and interindividual genetic susceptibility. Treatment-related factors include fraction size (the dose delivered with each treatment), the total dose delivered, the volume of tissue treated, the type of radiation, and the use of chemotherapy. ( 4), both treatment- and patient-related factors influence acute toxicities during and following breast cancer irradiation. Thus, it is of paramount importance to have a better understanding of the factors related to radiation-induced side effects.Īs reviewed by Harper et al. Minimizing acute toxicity will significantly improve quality of life and may be related to better treatment compliance. Although radiotoxicity may not be directly related to patients' survival, it merits close attention. Radiation may differentially affect normal and tumor tissue because there is considerable heterogeneity with respect to different growth states and cellular composition between tumor and normal tissue ( 5). Thus, it is likely for patients to develop acute toxicities from radiotherapy in these tissues. Although radiotherapy precisely targets the tumor cells with high energy beams of radiation to minimize radiation exposure to normal tissue, normal tissues that rapidly proliferate, such as skin, gastrointestinal mucosa, and hematopoietic cells, are also relatively radiosensitive ( 4). Radiation therapy can also cause mitochondrial permeabilization due to the enhanced generation of ROS, triggering apoptosis ( 3). Oxidative stress, resulting from an excess of ROS and/or a decrease in antioxidant levels, provokes cell death through massive cellular damage to macromolecules, such as lipids, proteins, and nucleic acids, or indirectly through triggering abnormal signaling and cell cycle regulation ( 2). Radiation therapy exerts antitumor effects through increased formation of reactive oxygen species (ROS ref. Regression trees may be useful in future studies to examine the contributions of multiple factors to individual susceptibility to adverse effects of cancer treatment. 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.Ĭonclusions: Associations between BMI and radiotoxicity risk may be most apparent among women with genotypes related to higher levels of oxidative stress. Overweight/obesity was not a strong risk factor among women with other eNOS and MPO genotypes. 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 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. However, relationships between overweight/obesity and radiotoxicity risk seemed to be modified by eNOS and MPO genotypes associated with higher generation of nitric oxide and ROS, respectively. Results: Genotypes associated with higher levels of reactive oxygen species (ROS) were not associated with risk of radiotoxicity.
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.
Genotypes were determined by matrix-assisted laser desorption/ionization time-of-flight. 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.Įxperimental Design: Cases ( n = 446) were Caucasian women with breast cancer who received radiotherapy following lumpectomy.
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