title: Association of polymorphisms in genes of the homologous recombination DNA repair pathway and thyroid cancer risk.
abstract: BACKGROUND
  Ionizing radiation exposure has been pointed out as a risk factor for thyroid cancer. The double-strand breaks induced by this carcinogen are usually repaired by homologous recombination repair pathway, a pathway that includes several polymorphic genes. Since there is a scarcity of data about the involvement of these gene polymorphisms in thyroid cancer susceptibility, we carried out a case-control study in a Caucasian Portuguese population.
  
  
  METHODS
  We genotyped 109 patients and 217 controls for the XRCC3 T241M, XRCC2 R188H, NBS1 E185Q, and RAD51 Ex1-59G>T polymorphisms to evaluate their potential main effects on risk for this pathology.
  
  
  RESULTS
  The results obtained showed that for the RAD51 Ex1-59G>T polymorphism, the homozigosity for the variant allele was associated with an almost significant increase of the odds ratio (OR) (adjusted OR = 1.9; confidence interval 95%: 1.0-3.5; p = 0.057). Additionaly, when the XRCC3 T241M data were analyzed concerning the presence of at least one wild-type allele, we observed that individuals homozygous for the variant allele had a higher risk for thyroid cancer (adjusted OR = 2.0; confidence interval 95%: 1.1-3.6; p = 0.026). When the data were analyzed according to the number of RAD51 Ex1-59G>T and XRCC3 T241M variant alleles, the coexistence of three or more variant alleles in either gene was associated to a significant higher risk (three variant alleles: adjusted OR = 2.9, p = 0.036; four variant alleles: adjusted OR = 8.0, p = 0.006).
  
  
  CONCLUSIONS
  Since XRCC3 is involved in the assembly and stabilization of RAD51 protein multimers at double-strand break sites, we cannot exclude that the interaction of both polymorphisms can lead to a decreased DNA repair capacity and consequently increased risk for thyroid cancer.
authors.affiliation: Department of Genetics, Faculty of Medical Sciences, New University of Lisbon, P-1349-008 Lisbon, Portugal.
authors.forename: Helder Novais
authors.initials: HN
authors.lastname: Bastos
authors.forename: Mónica Rego
authors.initials: MR
authors.lastname: Antão
authors.forename: Susana N
authors.initials: SN
authors.lastname: Silva
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Azevedo
authors.forename: Isabel
authors.initials: I
authors.lastname: Manita
authors.forename: Valdemar
authors.initials: V
authors.lastname: Teixeira
authors.forename: Julieta Esperança
authors.initials: JE
authors.lastname: Pina
authors.forename: Octávia Monteiro
authors.initials: OM
authors.lastname: Gil
authors.forename: Teresa Cruz
authors.initials: TC
authors.lastname: Ferreira
authors.forename: Edward
authors.initials: E
authors.lastname: Limbert
authors.forename: José
authors.initials: J
authors.lastname: Rueff
authors.forename: Jorge Francisco
authors.initials: JF
authors.lastname: Gaspar
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D004260:DNA Repair / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011174:Portugal / Q000453:epidemiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D015398:Signal Transduction / Q000235:genetics; D012907:Smoking / Q000453:epidemiology; D013964:Thyroid Neoplasms / Q000453:epidemiology* / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm