Genetic Polymorphisms in Genes Related to Oxidative Stress (GSTP1, GSTM1, GSTT1, CAT, MnSOD, MPO, eNOS) and Survival of Rectal Cancer Patients after Radiotherapy

Radiotherapy exerts part of its antineoplastic effect by generating oxidative stress, therefore genetic variation inoxidative stress-related enzymes may influence survival of rectalcancer patients. We hypothesized that genetic polymorphismsassociated with higher amounts of reactive oxygen species (ROS)that exaggerate cytotoxic activity could improve survival afterradiotherapy. We followed 114 rectal cancer patients who receivedradiotherapy for an average of 42.5 months. Associations betweengenotypes (GSTP1, GSTM1,GSTT1, CAT,MnSOD, MPO andeNOS) and overall survival were assessed usingKaplan-Meier curves and Cox proportional hazards regression. Ashypothesized, patients carrying low ROS producingeNOS Glu298Asp asparagine allele showed anincreased hazard of death compared to homozygous carriers of theglutamine allele (hazard ratio (HR): 2.10, 95% confidenceinterval (CI): 1.01–4.38). However, carriers of low ROSproducing MPO G463A A allele had a decreasedhazard of death compared to patients homozygous for the G allele(HR: 0.44, 95% CI: 0.21–0.93) although patientshomozygous for the A allele had a slightly increased hazard (HR:1.12, 95% CI: 0.25–5.08). This explorative studyprovides first results and highlights the need for further, largerstudies to investigate association between genetic variation inoxidative stress genes and survival of rectal cancer patients whoreceived radiotherapy