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