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Association of Polymorphisms in ERCC2 Gene with Non-Familial Thyroid Cancer Risk

Departments of ¹ Genetics and ² Laboratorial Medicine, Faculty of Medical Sciences, New University of Lisbon; ³ Department of Nuclear Medicine, Portuguese Oncology Institute of Lisbon, Lisboa, Portugal; ⁴ Department of Radiological Protection and Nuclear Safety, Nuclear and Technological Institute, Sacavém, Portugal; and ⁵ Hospital Garcia da Horta, Unit of Endocrinology, Almada, Portugal

Requests for reprints: José Rueff, Department of Genetics, Faculty of Medical Sciences, New University of Lisbon, Rua da Junqueira 96, P-1349-008 Lisboa, Portugal. Phone: 351-213-610290; Fax: 351-213-622018. E-mail: rueff.gene{at}fcm.unl.pt

The ERCC2 protein is an evolutionary conserved ATP-dependent helicase that is associated with a TFIIH transcription factor complex and plays an important role in nucleotide excision repair. Mutations in this gene are responsible for xeroderma pigmentosum and also for Cocayne syndrome and trichothiodystrophy. Several single nucleotide polymorphisms have been identified in the ERCC2 locus. Among them, a G23591A polymorphism in the codon 312 results in an Asp Asn substitution in a conserved region and a A35931C polymorphism in the codon 751 results in a Lys Gln substitution. Because these polymorphisms have been associated with an increased risk for several types of cancers, we carried out an hospital based case-control study in a Caucasian Portuguese population to evaluate the potential role of these polymorphisms on the individual susceptibility to thyroid cancer. The results obtained did not reveal a significant association between each individual polymorphism studied (G23591A and A35931C) and an increased thyroid cancer risk, but individuals homozygous for non-wild-type variants are overrepresented in patients group. The evaluation of the different haplotypes generated by these polymorphisms showed that individuals simultaneously homozygous for rare variants of both polymorphisms have an increased risk for thyroid cancer [adjusted odds ratio (OR) 3.084; 95% confidence interval (95% CI), 1.347-7.061; P = 0.008] and for papillary thyroid–type tumors (adjusted OR, 2.997; 95% CI, 1.235-7.272; P = 0.015) but not for follicular thyroid–type tumors. These results suggest that genetic polymorphisms in this gene might be associated with individual susceptibility towards thyroid cancer, mainly papillary-type tumors, but larger studies are required to confirm these results.