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Breast Cancer Research
Published in: Breast Cancer Research 1/2015

Open Access 01-12-2015 | Research article

Genetic risk variants associated with in situ breast cancer

Authors: Daniele Campa, Myrto Barrdahl, Mia M. Gaudet, Amanda Black, Stephen J. Chanock, W. Ryan Diver, Susan M. Gapstur, Christopher Haiman, Susan Hankinson, Aditi Hazra, Brian Henderson, Robert N. Hoover, David J. Hunter, Amit D. Joshi, Peter Kraft, Loic Le Marchand, Sara Lindström, Walter Willett, Ruth C. Travis, Pilar Amiano, Afshan Siddiq, Dimitrios Trichopoulos, Malin Sund, Anne Tjønneland, Elisabete Weiderpass, Petra H. Peeters, Salvatore Panico, Laure Dossus, Regina G. Ziegler, Federico Canzian, Rudolf Kaaks

Published in: Breast Cancer Research | Issue 1/2015

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Abstract

Introduction

Breast cancer in situ (BCIS) diagnoses, a precursor lesion for invasive breast cancer, comprise about 20 % of all breast cancers (BC) in countries with screening programs. Family history of BC is considered one of the strongest risk factors for BCIS.

Methods

To evaluate the association of BC susceptibility loci with BCIS risk, we genotyped 39 single nucleotide polymorphisms (SNPs), associated with risk of invasive BC, in 1317 BCIS cases, 10,645 invasive BC cases, and 14,006 healthy controls in the National Cancer Institute’s Breast and Prostate Cancer Cohort Consortium (BPC3). Using unconditional logistic regression models adjusted for age and study, we estimated the association of SNPs with BCIS using two different comparison groups: healthy controls and invasive BC subjects to investigate whether BCIS and BC share a common genetic profile.

Results

We found that five SNPs (CDKN2BAS-rs1011970, FGFR2-rs3750817, FGFR2-rs2981582, TNRC9-rs3803662, 5p12-rs10941679) were significantly associated with BCIS risk (P value adjusted for multiple comparisons <0.0016). Comparing invasive BC and BCIS, the largest difference was for CDKN2BAS-rs1011970, which showed a positive association with BCIS (OR = 1.24, 95 % CI: 1.11–1.38, P = 1.27 x 10−4) and no association with invasive BC (OR = 1.03, 95 % CI: 0.99–1.07, P = 0.06), with a P value for case-case comparison of 0.006. Subgroup analyses investigating associations with ductal carcinoma in situ (DCIS) found similar associations, albeit less significant (OR = 1.25, 95 % CI: 1.09–1.42, P = 1.07 x 10−3). Additional risk analyses showed significant associations with invasive disease at the 0.05 level for 28 of the alleles and the OR estimates were consistent with those reported by other studies.

Conclusions

Our study adds to the knowledge that several of the known BC susceptibility loci are risk factors for both BCIS and invasive BC, with the possible exception of rs1011970, a putatively functional SNP situated in the CDKN2BAS gene that may be a specific BCIS susceptibility locus.
Appendix
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Metadata
Title
Genetic risk variants associated with in situ breast cancer
Authors
Daniele Campa
Myrto Barrdahl
Mia M. Gaudet
Amanda Black
Stephen J. Chanock
W. Ryan Diver
Susan M. Gapstur
Christopher Haiman
Susan Hankinson
Aditi Hazra
Brian Henderson
Robert N. Hoover
David J. Hunter
Amit D. Joshi
Peter Kraft
Loic Le Marchand
Sara Lindström
Walter Willett
Ruth C. Travis
Pilar Amiano
Afshan Siddiq
Dimitrios Trichopoulos
Malin Sund
Anne Tjønneland
Elisabete Weiderpass
Petra H. Peeters
Salvatore Panico
Laure Dossus
Regina G. Ziegler
Federico Canzian
Rudolf Kaaks
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2015
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-015-0596-x

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