Identification of epistatic interactions through genome-wide association studies in sporadic medullary and juvenile papillary thyroid carcinomas.

Abstract

BACKGROUND:

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. 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.

METHODS:

We 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.

RESULTS:

We 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.

CONCLUSIONS:

Overall, 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.

• Authors: Berta Luzón-Toro, Marta Bleda, Elena Navarro, Luz García-Alonso, Macarena Ruiz-Ferrer, Ignacio Medina, Marta Martín-Sánchez, Cristina Y Gonzalez, Raquel M Fernández, Ana Torroglosa, Guillermo Antiñolo, Joaquin Dopazo, Salud Borrego
• Journal: BMC medical genomics (BMC Med Genomics) Vol. 8 Pg. 83 (Dec 21 2015) ISSN: 1755-8794 [Electronic] England
• PMID: 26690675 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Adolescent
• Carcinoma (genetics)
• Carcinoma, Neuroendocrine (genetics)
• Carcinoma, Papillary
• Case-Control Studies
• Child
• Child, Preschool
• Epistasis, Genetic
• Female
• Genetic Predisposition to Disease (genetics)
• Genome-Wide Association Study
• Humans
• Male
• Polymorphism, Single Nucleotide
• Thyroid Cancer, Papillary
• Thyroid Neoplasms (genetics)
• Young Adult