title: Polymorphisms in RAD51, XRCC2 and XRCC3 genes of the homologous recombination repair in colorectal cancer--a case control study.
abstract: XRCC2 and XRCC3 proteins are structurally and functionally related to RAD51 which play an important role in the homologous recombination, the process frequently involved in cancer transformation. In our previous work we show that the 135G>C polymorphism (rs1801320) of the RAD51 gene can modify the effect of the Thr241Met polymorphism (rs861539) of the XRCC3 gene. We tested the association between the 135G>C polymorphism of the RAD51 gene, the Thr241Met polymorphism of the XRCC3 gene and the Arg188His polymorphism (rs3218536) of the XRCC2 gene and colorectal cancer risk and clinicopathological parameters. Polymorphisms were evaluated by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) in 100 patients with invasive adenocarcinoma of the colon and in 100 sex, age and ethnicity matched cancer-free controls. We stratified the patients by genotypes, tumour Duke's and TNM stage and calculated the linkage of each genotype with each stratum. Carriers of Arg188Arg/Me241tMet, His188His/Thr241Thr and His188His/G135G genotypes had an increased risk of colorectal cancer occurrence (OR 5.70, 95% CI 1.10-29.5; OR 12.4, 95% CI 1.63-94.9; OR 5.88, 95% CI 1.21-28.5, respectively). The C135C genotype decreased the risk of colorectal cancer singly (OR 0.06, 95% CI 0.02-0.22) as well as in combination with other two polymorphisms. TNM and Duke's staging were not related to any of these polymorphisms. Our results suggest that the 135G>C polymorphism of the RAD51 gene can be an independent marker of colorectal cancer risk. The Thr241Met polymorphism of the XRCC3 gene and the Arg188His polymorphism of the XRCC2 gene can modify the risk of colorectal cancer.
authors.affiliation: Laboratory of DNA Repair, Department of Molecular Genetics, University of Lodz, and Department of Surgical Oncology, N. Copernicus Hospital, Banacha 12/16, 90-237, Lodz, Poland.
authors.forename: Renata
authors.initials: R
authors.lastname: Krupa
authors.forename: Tomasz
authors.initials: T
authors.lastname: Sliwinski
authors.forename: Maria
authors.initials: M
authors.lastname: Wisniewska-Jarosinska
authors.forename: Jan
authors.initials: J
authors.lastname: Chojnacki
authors.forename: Maja
authors.initials: M
authors.lastname: Wasylecka
authors.forename: Lukasz
authors.initials: L
authors.lastname: Dziki
authors.forename: Jan
authors.initials: J
authors.lastname: Morawiec
authors.forename: Janusz
authors.initials: J
authors.lastname: Blasiak
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D051135:Rad51 Recombinase / Q000235:genetics*
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; C110901:X-ray repair cross complementing protein 3; C113187:XRCC2 protein, human; C495153:RAD51 protein, human; D051135:Rad51 Recombinase