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Breast Cancer Research
Published in: Breast Cancer Research 6/2010

Open Access 01-12-2010 | Research article

A genome-wide association scan on estrogen receptor-negative breast cancer

Authors: Jingmei Li, Keith Humphreys, Hatef Darabi, Gustaf Rosin, Ulf Hannelius, Tuomas Heikkinen, Kristiina Aittomäki, Carl Blomqvist, Paul DP Pharoah, Alison M Dunning, Shahana Ahmed, Maartje J Hooning, Antoinette Hollestelle, Rogier A Oldenburg, Lars Alfredsson, Aarno Palotie, Leena Peltonen-Palotie, Astrid Irwanto, Hui Qi Low, Garrett HK Teoh, Anbupalam Thalamuthu, Juha Kere, Mauro D'Amato, Douglas F Easton, Heli Nevanlinna, Jianjun Liu, Kamila Czene, Per Hall

Published in: Breast Cancer Research | Issue 6/2010

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Abstract

Introduction

Breast cancer is a heterogeneous disease and may be characterized on the basis of whether estrogen receptors (ER) are expressed in the tumour cells. ER status of breast cancer is important clinically, and is used both as a prognostic indicator and treatment predictor. In this study, we focused on identifying genetic markers associated with ER-negative breast cancer risk.

Methods

We conducted a genome-wide association analysis of 285,984 single nucleotide polymorphisms (SNPs) genotyped in 617 ER-negative breast cancer cases and 4,583 controls. We also conducted a genome-wide pathway analysis on the discovery dataset using permutation-based tests on pre-defined pathways. The extent of shared polygenic variation between ER-negative and ER-positive breast cancers was assessed by relating risk scores, derived using ER-positive breast cancer samples, to disease state in independent, ER-negative breast cancer cases.

Results

Association with ER-negative breast cancer was not validated for any of the five most strongly associated SNPs followed up in independent studies (1,011 ER-negative breast cancer cases, 7,604 controls). However, an excess of small P-values for SNPs with known regulatory functions in cancer-related pathways was found (global P = 0.052). We found no evidence to suggest that ER-negative breast cancer shares a polygenic basis to disease with ER-positive breast cancer.

Conclusions

ER-negative breast cancer is a distinct breast cancer subtype that merits independent analyses. Given the clinical importance of this phenotype and the likelihood that genetic effect sizes are small, greater sample sizes and further studies are required to understand the etiology of ER-negative breast cancers.
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Metadata
Title
A genome-wide association scan on estrogen receptor-negative breast cancer
Authors
Jingmei Li
Keith Humphreys
Hatef Darabi
Gustaf Rosin
Ulf Hannelius
Tuomas Heikkinen
Kristiina Aittomäki
Carl Blomqvist
Paul DP Pharoah
Alison M Dunning
Shahana Ahmed
Maartje J Hooning
Antoinette Hollestelle
Rogier A Oldenburg
Lars Alfredsson
Aarno Palotie
Leena Peltonen-Palotie
Astrid Irwanto
Hui Qi Low
Garrett HK Teoh
Anbupalam Thalamuthu
Juha Kere
Mauro D'Amato
Douglas F Easton
Heli Nevanlinna
Jianjun Liu
Kamila Czene
Per Hall
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 6/2010
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2772

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