The role of common variants of non-homologous end-joining repair genes XRCC4, LIG4 and Ku80 in thyroid cancer risk

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Abstract

Variations, such as single nucleotide polymorphisms (SNPs) in DNA damage repair genes have been pointed out as possible factors to cancer predisposition. Ionizing radiation (IR) induces DNA double strand breaks (DSBs) and is the main recognized risk factor for thyroid cancer. However, most of the patients do not show chronic contact with IR and the other factors have non-concordant data. Thus, thyroid cancer could be due to gene variations in association with certain exogenous factors. One of the pathways that repair DSBs is DNA non-homologous end-joining (NHEJ) that comprises several polymorphic genes. We intend to study the role of polymorphic variants in XRCC4, LIG4 and Ku80 genes, since there is scarcity of data on the role of these genes in thyroid cancer susceptibility. We carried out a hospital-based case-control study in a Caucasian Portuguese population (109 patients and 217 controls) to estimate the potential role of the XRCC4 (N298S and T134I), LIG4 (T9I) and Ku80 (Ex21-238G-A, Ex21+338T-C, Ex21-352C-A, Ex21+466A-G) polymorphisms in the individual susceptibility for this disease. The results here reported do not associate these polymorphisms with susceptibility for non-familial thyroid cancer. However, when the data were analyzed according to the type of tumour, significant results for Ku80 Ex21-238G-A and Ex21+466A-G were found for papillary tumours (adjusted OR = 2.281: 95% CI = 1.063-4.894: P=0.034). Taken together these results suggest that some of these variants in NHEJ genes can contribute to thyroid cancer susceptibility. However, further studies with a larger sample size will be needed to support our results.
Original languageEnglish
Pages (from-to)1079-1085
Number of pages7
JournalOncology Reports
Volume24
Issue number4
Publication statusPublished - 1 Jan 2010

Keywords

  • genetic susceptibility
  • thyroid cancer
  • non-homologous end-joining repair
  • DNA repair polymorphisms

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