Skip to main content
eScholarship
Open Access Publications from the University of California

UC San Diego

UC San Diego Previously Published Works bannerUC San Diego

A common polymorphism in the retinoic acid pathway modifies adrenocortical carcinoma age-dependent incidence.

  • Author(s): Surakhy, Mirvat
  • Wallace, Marsha
  • Bond, Elisabeth
  • Grochola, Lukasz Filip
  • Perez, Husein
  • Di Giovannantonio, Matteo
  • Zhang, Ping
  • Malkin, David
  • Carter, Hannah
  • Parise, Ivy Zortea S
  • Zambetti, Gerard
  • Komechen, Heloisa
  • Paraizo, Mariana M
  • Pagadala, Meghana S
  • Pinto, Emilia M
  • Lalli, Enzo
  • Figueiredo, Bonald C
  • Bond, Gareth L
  • et al.
Abstract

Background

Genome-wide association studies (GWASs) have enriched the fields of genomics and drug development. Adrenocortical carcinoma (ACC) is a rare cancer with a bimodal age distribution and inadequate treatment options. Paediatric ACC is frequently associated with TP53 mutations, with particularly high incidence in Southern Brazil due to the TP53 p.R337H (R337H) germline mutation. The heterogeneous risk among carriers suggests other genetic modifiers could exist.

Methods

We analysed clinical, genotype and gene expression data derived from paediatric ACC, R337H carriers, and adult ACC patients. We restricted our analyses to single nucleotide polymorphisms (SNPs) previously identified in GWASs to associate with disease or human traits.

Results

A SNP, rs971074, in the alcohol dehydrogenase 7 gene significantly and reproducibly associated with allelic differences in ACC age-of-onset in both cohorts. Patients homozygous for the minor allele were diagnosed up to 16 years earlier. This SNP resides in a gene involved in the retinoic acid (RA) pathway and patients with differing levels of RA pathway gene expression in their tumours associate with differential ACC progression.

Conclusions

These results identify a novel genetic component to ACC development that resides in the retinoic acid pathway, thereby informing strategies to develop management, preventive and therapeutic treatments for ACC.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
Current View