title: Association between single nucleotide polymorphisms (SNPs) of XRCC2 and XRCC3 homologous recombination repair genes and ovarian cancer in Polish women.
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.
authors.affiliation: Department of Obstetrics and Gynaecology, Regional Hospital in Kalisz, Poland.
authors.forename: Magdalena M
authors.initials: MM
authors.lastname: Michalska
authors.affiliation: Department of Obstetrics and Gynaecology, Regional Hospital in Kalisz, Poland; Cathedral of Mother's and Child's Health, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Samulak
authors.affiliation: Laboratory of Cancer Genetics, Department of Pathology, Institute of Polish Mother's Memorial Hospital, Lodz, Poland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Romanowicz
authors.affiliation: Laboratory of Cancer Genetics, Department of Pathology, Institute of Polish Mother's Memorial Hospital, Lodz, Poland.
authors.forename: Filip
authors.initials: F
authors.lastname: Jabłoński
authors.affiliation: Laboratory of Cancer Genetics, Department of Pathology, Institute of Polish Mother's Memorial Hospital, Lodz, Poland. Electronic address: smolbea@wp.pl.
authors.forename: Beata
authors.initials: B
authors.lastname: Smolarz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D011044:Poland; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D059767:Recombinational DNA Repair / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C110901:X-ray repair cross complementing protein 3; C113187:XRCC2 protein, human
keywords: Gene polymorphism; Ovarian cancer; XRCC2; XRCC3