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 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.
Funke
Silvia
S
Division of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Risch
Angela
A
Nieters
Alexandra
A
Hoffmeister
Michael
M
Stegmaier
Christa
C
Seiler
Christoph M
CM
Brenner
Hermann
H
Chang-Claude
Jenny
J
J Leukoc Biol. 2005 May;77(5):598-625
15689384
Am J Epidemiol. 2005 Nov 15;162(10):943-52
16192345
Am J Epidemiol. 2000 Jan 1;151(1):7-32
10625170
Nucleic Acids Res. 1988 Feb 11;16(3):1215
3344216
Z Gastroenterol. 2008 Aug;46(8):799-840
18759205
Arch Toxicol. 2004 Jul;78(7):390-6
15007541
EMBO J. 1999 Mar 1;18(5):1321-34
10064598
Cancer Epidemiol Biomarkers Prev. 2006 Jun;15(6):1217-22
16775184
J Natl Cancer Inst. 1996 Dec 18;88(24):1853-6
8961976
Cancer Res. 2005 Feb 1;65(3):1105-11
15705913
Breast Cancer Res Treat. 2006 Nov;100(2):213-8
16821086
Eur J Biochem. 1998 Feb 15;252(1):1-15
9523706
Br J Cancer. 2004 Jul 19;91(2):344-54
15213713
J Hypertens. 2002 Oct;20(10):2023-7
12359981
Annu Rev Biochem. 1995;64:97-112
7574505
Crit Rev Biochem Mol Biol. 1995;30(6):445-600
8770536
Radiother Oncol. 1999 May;51(2):153-60
10435807
Cancer Res. 2006 Jul 1;66(13):6459-62
16818612
J Biol Chem. 1996 Jun 14;271(24):14412-20
8662930
Free Radic Biol Med. 1998 Mar 1;24(4):586-93
9559871
Free Radic Biol Med. 2001 Mar 1;30(5):500-5
11182520
J Biol Chem. 1997 Apr 11;272(15):10004-12
9092542
Carcinogenesis. 1998 May;19(5):711-21
9635855