Association of Polymorphisms in Genes of the Homologous Recombination DNA Repair Pathway and Thyroid Cancer Risk

Hélder Novais Bastos, Mónica Rego Antão, Susana N Silva, Ana P. Azevedo, Isabel Manita , Julieta Esperança Pina, Valdemar Teixeira, Octávia Monteiro Gil, Teresa Cruz Ferreira, Edward S. Limbert, José Rueff, Jorge F. Gaspar

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1067-1076
Number of pages10
JournalThyroid
Volume19
Issue number10
DOIs
Publication statusPublished - 5 Oct 2009

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