Abstract
BackgroundThe molecular mechanisms leading to sporadic medullary thyroid carcinoma (sMTC) and juvenile papillary thyroid carcinoma (PTC), two rare tumours of the thyroid gland, remain poorly understood. Genetic studies on thyroid carcinomas have been conducted, although just a few loci have been systematically associated. Given the difficulties to obtain single-loci associations, this work expands its scope to the study of epistatic interactions that could help to understand the genetic architecture of complex diseases and explain new heritable components of genetic risk.MethodsWe carried out the first screening for epistasis by Multifactor-Dimensionality Reduction (MDR) in genome-wide association study (GWAS) on sMTC and juvenile PTC, to identify the potential simultaneous involvement of pairs of variants in the disease.ResultsWe have identified two significant epistatic gene interactions in sMTC (CHFR-AC016582.2 and C8orf37-RNU1-55P) and three in juvenile PTC (RP11-648k4.2-DIO1, RP11-648k4.2-DMGDH and RP11-648k4.2-LOXL1). Interestingly, each interacting gene pair included a non-coding RNA, providing thus support to the relevance that these elements are increasingly gaining to explain carcinoma development and progression.ConclusionsOverall, this study contributes to the understanding of the genetic basis of thyroid carcinoma susceptibility in two different case scenarios such as sMTC and juvenile PTC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-015-0160-7) contains supplementary material, which is available to authorized users.
Highlights
The molecular mechanisms leading to sporadic medullary thyroid carcinoma and juvenile papillary thyroid carcinoma (PTC), two rare tumours of the thyroid gland, remain poorly understood
Studies have been focused on the analysis of specific single nucleotide polymorphisms (SNPs)/haplotypes and significant associations to sporadic medullary thyroid carcinoma (sMTC) have been described for different susceptibility genes, suggesting that this phenotype may be caused by a combination of multiple common genetic variants [5,6,7]
We report here the first study that combines a screening for epistasis by Multifactor-dimensionality reduction (MDR) in genome-wide association study (GWAS) on these two rare thyroid carcinoma types
Summary
The molecular mechanisms leading to sporadic medullary thyroid carcinoma (sMTC) and juvenile papillary thyroid carcinoma (PTC), two rare tumours of the thyroid gland, remain poorly understood. The few pathologic studies carried out in jPTC point to exposure to ionizing radiation as the only known environmental risk factor [12, 13]. It have reported several SNPs associated with the risk of PTC in the absence of radiation, most of them were carried out with older patients (mean age around 45 years) and/or using somatic rather than germline DNA [6]. As in the case of sMTC, the molecular mechanisms that account for jPTC or explain the development of this tumour remain largely unknown
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