Genome-wide association and epistatic studies in sporadic medullary and juvenile papillary thyroid carcinomas

Although many genetic studies on thyroid cancers using different approaches have been conducted, just a few loci have been systematically associated. Given the difficulties to obtain single-loci associations this work focuses on the study of epistatic interactions that could help to understand the genetic architecture of complex diseases and explain new heritable components of genetic risk. To our knowledge, this is the first genome-wide epistatic screening for epistasis ever performed in thyroid cancer. Here, we analyzed both sporadic medullary thyroid cancer (sMTC) and juvenile papillary thyroid cancer (PTC) patients. 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 cancer development and progression. Overall, this study contributes to the understanding of the genetic basis of thyroid cancer susceptibility in two different case scenarios such as sMTC and juvenile PTC. It opens further ways of knowledge of new heritable components of genetic risk to disease through association and statistical viewpoints. DNA derived from peripheral blood was hybridized to Affymetrix Genome-Wide Human SNP 6.0 arrays. Two different series of patients were recruited, one with 66 sporadic medullary thyroid cancer (sMTC) patients, with no family history suggestive of MEN 2. The second group compiled 30 juvenile patients with PTC (under 18 years of age) with no history of head and neck irradiation. Additionally, 129 healthy controls comprising unselected, unrelated, race, age, and sex-matched individuals without previous thyroid-related disease history were recruited.