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

Abstract

Radiotherapy exerts part of its antineoplastic effect by generating oxidative stress, therefore genetic variation in oxidative stress-related enzymes may influence survival of rectal cancer patients. We hypothesized that genetic polymorphisms associated with higher amounts of reactive oxygen species (ROS) that exaggerate cytotoxic activity could improve survival after radiotherapy. We followed 114 rectal cancer patients who received radiotherapy for an average of 42.5 months. Associations between genotypes (GSTP1, GSTM1, GSTT1, CAT, MnSOD, MPO and eNOS) and overall survival were assessed using Kaplan-Meier curves and Cox proportional hazards regression. As hypothesized, patients carrying low ROS producing eNOS Glu298Asp asparagine allele showed an increased hazard of death compared to homozygous carriers of the glutamine allele (hazard ratio (HR): 2.10, 95% confidence interval (CI): 1.01–4.38). However, carriers of low ROS producing MPO G463A A allele had a decreased hazard of death compared to patients homozygous for the G allele (HR: 0.44, 95% CI: 0.21–0.93) although patients homozygous for the A allele had a slightly increased hazard (HR: 1.12, 95% CI: 0.25–5.08). This explorative study provides first results and highlights the need for further, larger studies to investigate association between genetic variation in oxidative stress genes and survival of rectal cancer patients who received radiotherapy.

Microenvironment in Vagina as a Key-Player on Cervical Cancer: Interaction of Polymorphic Genetic Variants and Vaginal Microbiome as Co-Factors

“…In a case-control study, we observed a greater risk for developing ICC associated with the homozygote genotype TT of CAT polymorphism C-262 T polymorphism of the CAT gene (OR = 3.03, 95% CI 1.46-6.29, P = 0.003) [31]. Similarly to other cancers types, the T variant of this polymorphism is associated to a decreased enzyme activity, generating high levels of ROS [32][33][34]. The interaction of CC genotype of p22phox polymorphism and the TT genotype of CAT leads to a higher risk for ICC (OR = 3.95, 95% CI 1.07-14.52, P = 0.032) [31].…”

Response of glutathione S‐transferase Pi (GSTP1) to neoadjuvant therapy in rectal adenocarcinoma

“…Their weakness, however, is that genotype may not always correlate with phenotype [31]. Funke et al [32] found no overall relationship between GSTP1 genotype and survival postradiotherapy for rectal cancer. Similarly, Paez et al [33] did not detect a relationship between GSTP1 polymorphisms and progression-free survival, overall survival or response to preoperative chemoradiotherapy in patients with rectal cancer.…”

Common Polymorphisms in Angiogenesis

“…In NSCLC a decreased risk of pneumonitis was noted in carriers of the low-activity E298D allele (Hildebrandt et al 2010); however, that effect is almost certainly not attributable to differences in angiogenesis, but rather to inflammatory differences. Similarly the decreased rectal cancer survival observed in carriers of the E298D allele following radiotherapy (Funke et al 2009) are likely a result of decreased low reactive oxygen production rather than any angiogenic effects.…”