Polymorphisms in matricellular SPP1 and SPARC contribute to susceptibility to papillary thyroid cancer

Genomics. 2020 Nov;112(6):4959-4967. doi: 10.1016/j.ygeno.2020.09.018. Epub 2020 Sep 9.

Abstract

There is a compelling need to identify novel genetic variants for papillary thyroid cancer (PTC) susceptibility. The Cancer Genome Atlas (TCGA) data showed associations between SPP1 and SPARC mRNA overexpression and aggressive behaviors of PTC, which prompted us to assess potential associations between genetic variants in these genes and PTC risk. Three highly linked SPARC loci (rs1054204, rs3210714, and rs3549) contributed to reduced PTC risk under a codominant model (odds ratio [OR], 0.79-0.80). Variant CAG alleles at these loci significantly enhanced SPARC transcription activation upon cotransfection with miR-29b and miR-495 when compared to the common alleles GGC (all P < 0.05). The three SPARC polymorphisms interacted with SPP1 rs4754, with elevated joint ORs of 2.43, 2.52, and 2.52, respectively. Additionally, interaction between SPP1 rs2358744 and SPARC rs2304052 was observed. Our study revealed associations between SPP1 and SPARC polymorphisms that, individually or in combination, are involved in PTC susceptibility.

Keywords: Genetic model; Papillary thyroid cancer; Single nucleotide polymorphism; Susceptibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • MicroRNAs / metabolism
  • Middle Aged
  • Models, Genetic
  • Osteonectin / genetics*
  • Osteonectin / metabolism
  • Osteopontin / genetics*
  • Osteopontin / metabolism
  • Polymorphism, Single Nucleotide
  • RNA, Messenger / metabolism
  • Thyroid Cancer, Papillary / genetics*
  • Thyroid Cancer, Papillary / metabolism
  • Thyroid Cancer, Papillary / pathology
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / pathology

Substances

  • 3' Untranslated Regions
  • MicroRNAs
  • Osteonectin
  • RNA, Messenger
  • SPARC protein, human
  • SPP1 protein, human
  • Osteopontin