Comprehensive genetic assessment of the ESR1 locus identifies a risk region for endometrial cancer.

Endocrine-related Cancer
Tracy O'MaraAmanda B Spurdle

Abstract

Excessive exposure to estrogen is a well-established risk factor for endometrial cancer (EC), particularly for cancers of endometrioid histology. The physiological function of estrogen is primarily mediated by estrogen receptor alpha, encoded by ESR1. Consequently, several studies have investigated whether variation at the ESR1 locus is associated with risk of EC, with conflicting results. We performed comprehensive fine-mapping analyses of 3633 genotyped and imputed single nucleotide polymorphisms (SNPs) in 6607 EC cases and 37 925 controls. There was evidence of an EC risk signal located at a potential alternative promoter of the ESR1 gene (lead SNP rs79575945, P=1.86×10(-5)), which was stronger for cancers of endometrioid subtype (P=3.76×10(-6)). Bioinformatic analysis suggests that this risk signal is in a functionally important region targeting ESR1, and eQTL analysis found that rs79575945 was associated with expression of SYNE1, a neighbouring gene. In summary, we have identified a single EC risk signal located at ESR1, at study-wide significance. Given SNPs located at this locus have been associated with risk for breast cancer, also a hormonally driven cancer, this study adds weight to the rationale for performing inform...Continue Reading

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Citations

May 3, 2016·Nature Genetics·Timothy Ht ChengAmanda B Spurdle
Apr 30, 2017·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Amanda B SpurdleJudy Kirk
Aug 10, 2018·International Journal of Cancer. Journal International Du Cancer·Robert NeffPaul J Goodfellow
Feb 19, 2020·Journal of Medical Genetics·Cemsel BafligilEmma J Crosbie
Jul 10, 2020·Clinical Epigenetics·Holly RussellAnnabelle Lewis
Oct 2, 2020·Archives of Gynecology and Obstetrics·Jutta PretscherEva Schwenke
Oct 5, 2016·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Christopher I AmosDouglas F Easton
Jan 17, 2021·Cancers·Sheetal ParidaDipali Sharma

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