GA GENOTYPE OF THE ARG280HIS POLYMORPHISM ON THE XRCC1 GENE: GENETIC SUSCEPTIBILITY GENOTYPE IN DIFFERENTIATED THYROID CARCINOMAS?
Kirnap NG1,*, Tutuncu NB1,2, Yalcin Y2, Cebi HPB2, Tutuncu T2,3, Nar A1, Verdi H2, Atac FB2
*Corresponding Author: Nazlı G. Kirnap, M.D., Department of Endocrinology and Metabolism, Başkent University Faculty of Medicine, Taskent Caddesi No. 77, Bahcelievler, 06490, Ankara, Turkey. Tel.: +90-(0)312-203-6868. Fax: +90-(0)312-304-2700. E-mail: kirnapnazli@hotmail.com
page: 73
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Abstract

Differentiated thyroid carcinomas (DTC) are the most common form of endocrine malignancies. The role of genetic variations in the development of papillary thyroid carcinoma (PTC) is approximately 60.0-70.0%. The X-ray repair cross-complementing group 1 (XRCC1) protein has an important role in DNA repair mechanisms and genomic polymorphisms of XRCC1 gene affect the function of the protein. In the present case-control study, we aimed to compare the genotype frequency distributions of XRCC1 single nucleotide polymorphisms (SNPs) in terms of the presence of other risk factors (Hashimoto’s thyroiditis, smoking, obesity, radiation exposure) in patients with thyroid nodules who had fine-needle aspiration biopsy (FNAB) and/or thyroid surgery due to thyroid cancer. The genotype frequency distributions of three common XRCC1 SNPs (Arg194Trp, Arg399Gln, Arg280His) were compared to those with DTC (n = 228), benign thyroid nodules (BTN, n = 100) and healthy controls (n = 93) in terms of certain pre defined risk factors such as the presence of Hashimoto’s thyroiditis, smoking, obesity, a family history of thyroid cancer and radiation exposure. The frequency of the GA genotype of Arg280His in DTC cases was found to be higher than in those with BTN and the healthy control group (p <0.001). The DTC group had the lowest frequency of AA genotype of Arg280His (35.5%, p <0.001). Among those with a family history of thyroid cancer, 78.9% had a GA genotype and 21.1% had the AA genotype of Arg280His (p = 0.004). The Arg280His GA genotype was more common in DTC than in cancer-free controls. The GA genotype frequency was also high in DTC cases with a family history of thyroid cancer



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