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

British Journal of Cancer
Mirvat SurakhyGareth L Bond

Abstract

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. 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. 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. These results identify a novel genetic component to ACC development that resides in ...Continue Reading

References

Jul 14, 1999·Developmental Genetics·L DeltourG Duester
Aug 2, 2001·Proceedings of the National Academy of Sciences of the United States of America·R C RibeiroR Sandrini
Oct 17, 2001·The Journal of Clinical Investigation·M Páez-PeredaG K Stalla
Apr 28, 2004·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·R C Ribeiro, B Figueiredo
Mar 12, 2005·Arquivos brasileiros de endocrinologia e metabologia·Emilia M PintoAna Claudia Latronico
Jul 22, 2005·Journal of Medical Genetics·B C FigueiredoR C Ribeiro
Sep 28, 2006·European Journal of Human Genetics : EJHG·Mariëlle W G RuijsLaura J Van't Veer
May 27, 2008·Nature Genetics·Mia HashibePaul Brennan
May 28, 2009·Nuclear Receptor Signaling·Cécile Rochette-Egly, Pierre Germain
Jun 23, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Alfredo BerrutiMassimo Terzolo
Jul 27, 2010·Advanced Drug Delivery Reviews·Nathan Bushue, Yu-Jui Yvonne Wan
Oct 29, 2010·The Journal of Nutrition·Tilman GruneHans K Biesalski
Sep 21, 2011·Molecular and Cellular Endocrinology·Jonathan D WassermanDavid Malkin
Apr 12, 2012·Nature Biotechnology·Philippe SanseauVincent Mooser
May 4, 2012·The New England Journal of Medicine·Martin FassnachtUNKNOWN FIRM-ACT Study Group
Aug 29, 2012·The Journal of Nutritional Biochemistry·Jarrett T WhelanLance C Bridges
Jun 5, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Gislaine CustódioBonald C Figueiredo
Jun 29, 2013·Cellular and Molecular Life Sciences : CMLS·Diana Rita SzabóPeter Igaz
Oct 10, 2013·The Journal of Biological Chemistry·Jaume AmengualJohannes von Lintig
Jan 7, 2015·Nature Reviews. Molecular Cell Biology·Thomas J Cunningham, Gregg Duester
Mar 7, 2015·Nature Communications·Emilia M PintoGerard P Zambetti
Jun 30, 2015·Nature Genetics·Matthew R NelsonPhilippe Sanseau
Mar 13, 2016·Seminars in Oncology·Iván P UrayPowel H Brown
Mar 25, 2016·Nature Reviews. Cancer·Giovanni StracquadanioGareth L Bond
May 12, 2016·Cancer Cell·Siyuan ZhengRoel G W Verhaak
Jun 17, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Emilia Modolo PintoGerard P Zambetti
Jul 9, 2016·Experimental Biology and Medicine·Lei WuDingbo Lin
Dec 13, 2016·Cancer Chemotherapy and Pharmacology·Jan S MorebAbdullah Khan
Mar 31, 2017·Science Translational Medicine·Chris FinanJuan P Casas
Jul 8, 2017·American Journal of Human Genetics·Peter M VisscherJian Yang

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Citations

Aug 21, 2020·European Journal of Human Genetics : EJHG·Christian P KratzDavid Malkin
Jan 24, 2021·The Lancet Child & Adolescent Health·Christian P KratzFranck Bourdeaut

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Datasets Mentioned

BETA
GSE76019
GSE76021

Methods Mentioned

BETA
genotyping
RNA-seq

Software Mentioned

gplots
qqman
survminer
reshape2
tidyr
R
R Base
ggplot2
dplyr
plyr

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