Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Dec 21:8:83.
doi: 10.1186/s12920-015-0160-7.

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

Berta Luzón-Toro  1   2 , Marta Bleda  3   4   5 , Elena Navarro  6   7 , Luz García-Alonso  8   9 , Macarena Ruiz-Ferrer  10   11 , Ignacio Medina  12   13 , Marta Martín-Sánchez  14   15 , Cristina Y Gonzalez  16   17 , Raquel M Fernández  18   19 , Ana Torroglosa  20   21 , Guillermo Antiñolo  22   23 , Joaquin Dopazo  24   25   26 , Salud Borrego  27   28
Affiliations

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

Berta Luzón-Toro et al. BMC Med Genomics. .

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.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Gene-gene interactions obtained in sMTC patients by MDR analyses. a a total of 29 GxG interactions were obtained, (b) from which three were significant based on cross-validation value (>0.5)
Fig. 2
Fig. 2
Gene-gene interactions obtained in jPTC patients by MDR analyses. a a total of 259 GxG interactions were obtained, (b) from which 133 were significant based on cross-validation value (>0.5)
Fig. 3
Fig. 3
Expression profiling for arrays in 18 PTC samples (a) DIO1, (b) DMGD and (c) LOXL1 genes. Figures adapted from GeoDataSets
See this image and copyright information in PMC

References

    1. Figge JJ. Epidemiology of thyroid cancer. In: Wartofsky LVND, editor. Thyroid Cancer: A Comprehensive Guide to Clinical Management. Totowa: Human Press; 1999.
    1. Randolph GW, Maniar D. Medullary carcinoma of the thyroid. Cancer Control. 2000;7(3):253–261. - PubMed
    1. Moline J EC: Multiple Endocrine Neoplasia Type 2. In: SourceGeneReviews® [Internet]. Edited by Pagon RA AM, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Dolan CR, Fong CT, Smith RJH, Stephens K, editors. Seattle: University of Washington, Seattle; 2005.
    1. Eng C, Clayton D, Schuffenecker I, Lenoir G, Cote G, Gagel RF, et al. The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis. Jama. 1996;276(19):1575–1579. doi: 10.1001/jama.1996.03540190047028. - DOI - PubMed
    1. Fernandez RM, Pecina A, Antinolo G, Navarro E, Borrego S. Analysis of RET polymorphisms and haplotypes in the context of sporadic medullary thyroid carcinoma. Thyroid. 2006;16(4):411–417. doi: 10.1089/thy.2006.16.411. - DOI - PubMed

Publication types

Supplementary concepts