Shabnam Abtahi1, Fatemeh Izadi Jahromi1, Mohammad Hossein Dabbaghmanesh2, Mahyar Malekzadeh1, Abbas Ghaderi3,4. 1. Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. 2. Endocrine and Metabolism Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. 3. Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. ghaderi@sums.ac.ir. 4. Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran. ghaderi@sums.ac.ir.
Abstract
PURPOSE: Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4 or CD152) is among the immune checkpoint molecules and its abnormal expression in cancer predisposed individuals might make the person more susceptible to tumor initiation and progression. Considering the implication of single-nucleotide polymorphisms (SNPs) in CTLA-4 gene expression and probably protein function, one can assume the involvement of these SNPs in neoplastic diseases. rs5742909 ( - 318C > T) and rs231775 ( + 49 A > G) are among the most commonly studied SNPs and have been considered as genetic factors related to thyroid diseases. In this cross-sectional study, we aimed to elucidate the association between these SNPs and susceptibility to various types of thyroid cancers. METHODS: We investigated the genetic polymorphisms of - 318C > T and + 49 A > G in the CTLA-4 gene by means of ARMS-PCR and RFLP-PCR, respectively, in 167 patients with thyroid carcinomas (papillary, follicular, and anaplastic). The results were then compared with a group of 100 age-sex matched healthy individuals. RESULTS: A statistically significant association was observed between the presence of G allele in + 49 A > G locus and thyroid carcinoma, when comparing cases and controls (OR = 2.10; 95% CI = 1.35-3.28; P = 0.001) and the frequency of heterozygotes (AG) was higher than homozygotes for allele A (AA), in patients with and papillary thyroid carcinoma (PTC). Regarding Hashimoto's thyroiditis, the frequencies of A allele and AA genotype in PTC patients were higher than Hashimoto patients with no history of cancer (OR = 4.67, 95% CI = 2.70-8.08, P < 0.0001; and, OR = 4.68, 95% CI = 1.84-11.91, P = 0.0012; respectively). However; we observed no difference among allele/genotype frequencies in regards to locus - 318C > T. CONCLUSION: In this study, we observed that G allele in + 49 A > G and possibly lower expression of mutated CTLA-4 molecule, is associated with higher susceptibility to thyroid carcinoma. Although the G allele frequency was higher in thyroid cancer patients, when justified for the presence of lymphocytic thyroiditis, the presence of A allele seemed to increase the odds for PTC in patients with Hashimoto's disease.
PURPOSE:Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4 or CD152) is among the immune checkpoint molecules and its abnormal expression in cancer predisposed individuals might make the person more susceptible to tumor initiation and progression. Considering the implication of single-nucleotide polymorphisms (SNPs) in CTLA-4 gene expression and probably protein function, one can assume the involvement of these SNPs in neoplastic diseases. rs5742909 ( - 318C > T) and rs231775 ( + 49 A > G) are among the most commonly studied SNPs and have been considered as genetic factors related to thyroid diseases. In this cross-sectional study, we aimed to elucidate the association between these SNPs and susceptibility to various types of thyroid cancers. METHODS: We investigated the genetic polymorphisms of - 318C > T and + 49 A > G in the CTLA-4 gene by means of ARMS-PCR and RFLP-PCR, respectively, in 167 patients with thyroid carcinomas (papillary, follicular, and anaplastic). The results were then compared with a group of 100 age-sex matched healthy individuals. RESULTS: A statistically significant association was observed between the presence of G allele in + 49 A > G locus and thyroid carcinoma, when comparing cases and controls (OR = 2.10; 95% CI = 1.35-3.28; P = 0.001) and the frequency of heterozygotes (AG) was higher than homozygotes for allele A (AA), in patients with and papillary thyroid carcinoma (PTC). Regarding Hashimoto's thyroiditis, the frequencies of A allele and AA genotype in PTC patients were higher than Hashimoto patients with no history of cancer (OR = 4.67, 95% CI = 2.70-8.08, P < 0.0001; and, OR = 4.68, 95% CI = 1.84-11.91, P = 0.0012; respectively). However; we observed no difference among allele/genotype frequencies in regards to locus - 318C > T. CONCLUSION: In this study, we observed that G allele in + 49 A > G and possibly lower expression of mutated CTLA-4 molecule, is associated with higher susceptibility to thyroid carcinoma. Although the G allele frequency was higher in thyroid cancerpatients, when justified for the presence of lymphocytic thyroiditis, the presence of A allele seemed to increase the odds for PTC in patients with Hashimoto's disease.
Authors: Christina Resende de Paiva; Christian Grønhøj; Ulla Feldt-Rasmussen; Christian von Buchwald Journal: Front Oncol Date: 2017-04-10 Impact factor: 6.244