ECE2014 Poster Presentations Thyroid Cancer (70 abstracts)
The effect of allelic variants of the thyroid hormone receptor β (THRB) gene on the incidence of papillary thyroid carcinoma
Anna Wojcicka 1, , Marek Roslon 3 , Malgorzata Czetwertynska 1, , Michal Swierniak 1, , Joanna Dlugosinska 4 , Adam Kot 1, , Rafal Ploski 6 , Aneta Hromada-Judycka 1 , Marta Swiech 1 & Krystian Jazdzewski 1,
1Genomic Medicine, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland; 2Centre of New Technologies, CENT, University of Warsaw, Warsaw, Poland; 3Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland; 4Department of Endocrine Oncology and Nuclear Medicine, Institute of Oncology, Maria Sklododowska-Curie Memorial Cancer Center, Warsaw, Poland; 5Department of Nuclear Medicine and Endocrine Oncology, Institute of Oncology, Maria Sklododowska-Curie Memorial Cancer Center, Gliwice, Poland; 6Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland.
Objectives: Papillary thyroid carcinoma (PTC) is the most common malignancy of the endocrine system. Its heritability is the highest among common cancers, as evidenced by family-based studies. Thyroid hormone receptor β gene (THRB), a known tumor suppressor, is crucial for the proper thyroid function, therefore its polymorphisms are likely to affect the risk for thyroid cancer.
Aim of the study: In order to identify alleles that might modify the risk and clinical presentation of PTC we genotyped the three functional SNPs of THRB, namely rs13066296, rs13097208 and rs6792725.
Materials and results: DNA extracted from blood of 1683 PTC patients and 1667 control subjects was analyzed by Sequenom iPLEX technology. The association study revealed a significant association between the rs6792725 GG genotype of the THRB gene and a risk of development of PTC (OR=1.20; 95% CI: 1.05–1.39; P=0.0078). The study also showed a significant association between the CTG haplotype (rs13066296–rs13097208–rs6792725) and a higher risk of development of PTC (OR=1.15; P=0.047). Clinical phenotype was found to be influenced by interactive impact of the SNPs in combination with gender. rs13066296 variant modifies the likelihood of more advanced disease in males compared to women. The risk for worse T-status significantly decreases with each additional variant allele (hetero- or homozygous state) in males compared to females (P=0.023). Moreover, analysis of interaction between rs13097208 and age revealed an interactive, protective impact on clinical stage. The risk of worse clinical stage significantly decreases in the presence of rs13097208 variant allele (P=0.034).
Conclusions: This is the first study identifying a polymorphism and a haplotype within the THRB gene that significantly predisposes to the development of PTC in a Polish population, and an important step in understanding the background of genetic predisposition to PTC.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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