title: Association of single nucleotide polymorphisms in SOD2, XRCC1 and XRCC3 with susceptibility for the development of adverse effects resulting from radiotherapy for prostate cancer.
abstract: The objective of this study was to determine whether an association exists between certain single nucleotide polymorphisms (SNPs), which have previously been linked with adverse normal tissue effects resulting from radiotherapy, and the development of radiation injury resulting from radiotherapy for prostate cancer. A total of 135 consecutive patients with clinically localized prostate cancer and a minimum of 1 year of follow-up who had been treated with radiation therapy, either brachytherapy alone or in combination with external-beam radiotherapy, with or without hormone therapy, were genotyped for SNPs in SOD2, XRCC1 and XRCC3. Three common late tissue toxicities were investigated: late rectal bleeding, urinary morbidity, and erectile dysfunction. Patients with the XRCC1 rs25489 G/A (Arg280His) genotype were more likely to develop erectile dysfunction after irradiation than patients who had the G/G genotype (67% compared to 24%; P=0.048). In addition, patients who had the SOD2 rs4880 T/C (Val16Ala) genotype exhibited a significant increase in grade 2 late rectal bleeding compared to patients who had either the C/C or T/T genotype for this SNP (8% compared to 0%; P=0.02). Finally, patients with the combination of the SOD2 rs4880 C/T genotype and XRCC3 rs861539 T/C (Thr241Met) genotype experienced a significant increase in grade 2 late rectal bleeding compared to patients without this particular genotypic arrangement (14% compared to 1%; P=0.002). These results suggest that SNPs in the SOD2, XRCC1 and XRCC3 genes are associated with the development of late radiation injury in patients treated with radiation therapy for prostate adenocarcinoma.
authors.affiliation: Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Burri
authors.forename: Richard G
authors.initials: RG
authors.lastname: Stock
authors.forename: Jamie A
authors.initials: JA
authors.lastname: Cesaretti
authors.forename: David P
authors.initials: DP
authors.lastname: Atencio
authors.forename: Sheila
authors.initials: S
authors.lastname: Peters
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Peters
authors.forename: Grace
authors.initials: G
authors.lastname: Fan
authors.forename: Nelson N
authors.initials: NN
authors.lastname: Stone
authors.forename: Harry
authors.initials: H
authors.lastname: Ostrer
authors.forename: Barry S
authors.initials: BS
authors.lastname: Rosenstein
mesh_terms: D000368:Aged; D004268:DNA-Binding Proteins / Q000235:genetics*; D007172:Erectile Dysfunction / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006470:Hemorrhage / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000532:radiotherapy*; D018787:Radiation Oncology; D011878:Radiotherapy / Q000009:adverse effects*; D012002:Rectal Diseases / Q000235:genetics / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics*; D016896:Treatment Outcome; D014570:Urologic Diseases / Q000235:genetics / Q000473:pathology; D000076105:X-ray Repair Cross Complementing Protein 1; D000099156:Superoxide Dismutase 2
chemical_list: D004268:DNA-Binding Proteins; D013482:Superoxide Dismutase; D000076105:X-ray Repair Cross Complementing Protein 1; D000099156:Superoxide Dismutase 2; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human