ASSOCIATION OF XRCC3 GENE POLYMORPHISMS WITH EARLY NORMAL TISSUE ADVERSE EVENTS AFTER PELVIC IRRADIATION FOR GYNECOLOGICAL MALIGNANCIES
COMPTES RENDUS DE L ACADEMIE BULGARE DES SCIENCES
Authors: Encheva, Elitsa; Yordanova, Iglika; Lakov, Teodor; Savov, Aleksei; Kremensky, Ivo; Mitev, Vanio; Kaneva, Radka; Hadjieva, Tatjana
Abstract
The aim of the study was to investigate the possible association of DNA repair gene polymorphisms and early radiation normal tissue adverse events in gynecological cancer patients. 109 patients with cervical and endometrial cancer received a conventional external pelvic irradiation after a radical surgery to a 50 Gy total dose. A four fields "box" technique was applied with 2D planning. The acute normal tissue adverse events were graded according to CTCAE v 3.0. From all normal tissue adverse event scores the highest score named "summarized clinical radiosensitivity" was selected for a statistical analysis. DNA was isolated from blood samples obtained prior to the beginning of radiotherapy. The genotyping of XRCC3 (241 Thr/Met, IVS5-14 17.893) SNPs was clone by PCR-RFLP. 109 patients completed the treatment course with no interruption. The majority of the patients developed grade 1 and 2 adverse events. 2% of the patients showed no early radiation adverse events when grades 4-5 were not recorded. Statistically significant correlation between the XRCC3 Codon 241 Thr/Met genotype and the degree of skin reactions was found in the analysis of patients divided into two (0-1 grade and 2-3 grade) and three groups (0 and 2-3 grade) (Fisher exact test, p < 0.05). In genotype T/T carriers 0-1 grade skin reactions prevail. XRCC3 Codon IVS5-14 (A > G) was not found to be associated with early radiation adverse events. The conclusion of the present study is that polymorphic T allele of XRCC3 Codon 241 Thr/Met (C > T) diminishes the risk of development of early moderate and severe adverse skin radiation events.
Association between single nucleotide polymorphisms (SNPs) of XRCC2 and XRCC3 homologous recombination repair genes and ovarian cancer in Polish women
EXPERIMENTAL AND MOLECULAR PATHOLOGY
Authors: Michalska, Magdalena M.; Samulak, Dariusz; Romanowicz, Hanna; Jablonski, Filip; Smolarz, Beata
Abstract
The variability, perceived in DNA repair genes, may be of clinical importance for evaluation of the risk of occurrence of a given type of cancer, its prophylactics and therapy. The aim of the present work was to evaluate associations between the risk of ovarian cancer and polymorphisms in the genes, encoding for two key proteins of homologous recombination: XRCC2 Arg188His (c. 563 G > A; rs3218536) and XRCC3 Thr241Met (c. 722 C> T; rs861539). The study consisted of 700 patients with ovarian cancer and 700 healthy subjects. Analysis of the gene polymorphisms was performed using PCR-RFLP (restriction length fragment polymorphism). We found a statistically significant increase of the 188His allele frequency (OR = 4.01; 95% CI = 3.40-4.72; p <.0001) of XRCC2 in ovarian cancer compared to healthy controls. There were no differences in the genotype and allele distributions and odds ratios of the XRCC3 Thr241Met polymorphism between patient and control groups. Association of these genetic polymorphisms with histological grading showed increased XRCC2 188Arg/His (OR = 33.0; 95% CI = 14.51-75.05; p <.0001) and 188His/His genotypes (OR = 9.37; 95% CI = 4.79-18.32; p <.0001) and XRCC3 241Thr/Met (OR = 24.28; 95% CI = 12.38-47.61; p <.0001) and 241Met/Met genotype frequencies (OR = 17.00; 95% CI = 8.42-34.28; p <.0001) in grading 1 (G1) as well as 188His (OR = 2.78; 95% CI = 2.11-3.69; p <.0001) and 241Met allele overrepresentation (OR = 2.59; 95% CI = 2.08-3.22; p <.0001) in G1 ovarian patients. Finally, with clinical FIGO staging under evaluation, an increase in XRCC2 188His/His homozygote and 188Arg/His heterozygote frequencies in staging I (SI) and XRCC3 Thr/Met heterozygote frequencies in SI was observed. The obtained results indicate that XRCC2 Arg188His and XRCC3 Thr241Met polymorphisms may be positively associated with the incidence of ovarian carcinoma in the population of Polish women. (C) 2016 Elsevier Inc. All rights reserved.