Role of genetic variants of autophagy genes in susceptibility for non-medullary thyroid cancer and patients outcome

PLoS One. 2014 Apr 16;9(4):e94086. doi: 10.1371/journal.pone.0094086. eCollection 2014.

Abstract

Autophagy is a central process in regulation of cell survival, cell death and proliferation and plays an important role in carcinogenesis, including thyroid carcinoma. Genetic variation in autophagy components has been demonstrated to influence the capacity to execute autophagy and is associated with disease susceptibility, progression and outcome. In the present study, we assessed whether genetic variation in autophagy genes contributes to susceptibility to develop thyroid carcinoma, disease progression and/or patient outcome. The results indicate that patients carrying the ATG5 single nucleotide polymorphisms rs2245214 have a higher probability to develop thyroid carcinoma (OR 1.85 (95% CI 1.04-3.23), P = 0.042). In contrast, no significant differences could be observed for the other genetic variants studied in terms of thyroid carcinoma susceptibility. Furthermore, none of the selected genetic variants were associated with clinical parameters of disease progression and outcome. In conclusion, genetic variation in ATG5, a central player in the autophagy process, is found to be associated with increased susceptibility for thyroid carcinoma, indicating a role for autophagy in thyroid carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autophagy / genetics*
  • Autophagy-Related Protein 5
  • Carcinoma / genetics*
  • Genetic Variation*
  • Genotype
  • Humans
  • Male
  • Microtubule-Associated Proteins / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Survival Analysis
  • Thyroid Neoplasms / genetics*

Substances

  • ATG5 protein, human
  • Autophagy-Related Protein 5
  • Microtubule-Associated Proteins

Grants and funding

TSP was supported by a Veni grant of the Netherlands Organization for Scientific Research (NWO). MGN was supported by a Vici grant of the Netherlands Organization for Scientific Research (NWO). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.