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

• Type: Article in International Scientific Journal
• Date: 2009

Authors

Bastos, HN (Author) Other; Antao, MR (Author) Other; Silva, SN (Author) Other; Azevedo, AP (Author) Other; Manita, I (Author) Other; Teixeira, V (Author) Other; Pina, JE (Author) Other; Gil, OM (Author) Other; Ferreira, TC (Author) Other; Limbert, E (Author) Other; Rueff, J (Author) Other; Gaspar, JF (Author) Other

Journal

Title: Thyroid

Vol. 19

Pages: 1067-1076

ISSN: 1050-7256

Publisher: Mary Ann Liebert

Indexing

ISI Web of Knowledge - 52 Citations

Scopus - 56 Citations

Other information

Authenticus ID: P-003-FN2

DOI: 10.1089/thy.2009.0099

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11