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Breast Cancer Research
Published in: Breast Cancer Research 2/2012

Open Access 01-04-2012 | Research article

Reproductive aging-associated common genetic variants and the risk of breast cancer

Authors: Chunyan He, Daniel I Chasman, Jill Dreyfus, Shih-Jen Hwang, Rikje Ruiter, Serena Sanna, Julie E Buring, Lindsay Fernández-Rhodes, Nora Franceschini, Susan E Hankinson, Albert Hofman, Kathryn L Lunetta, Giuseppe Palmieri, Eleonora Porcu, Fernando Rivadeneira, Lynda M Rose, Greta L Splansky, Lisette Stolk, André G Uitterlinden, Stephen J Chanock, Laura Crisponi, Ellen W Demerath, Joanne M Murabito, Paul M Ridker, Bruno H Stricker, David J Hunter

Published in: Breast Cancer Research | Issue 2/2012

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Abstract

Introduction

A younger age at menarche and an older age at menopause are well established risk factors for breast cancer. Recent genome-wide association studies have identified several novel genetic loci associated with these two traits. However, the association between these loci and breast cancer risk is unknown.

Methods

In this study, we investigated 19 and 17 newly identified single nucleotide polymorphisms (SNPs) from the ReproGen Consortium that have been associated with age at menarche and age at natural menopause, respectively, and assessed their associations with breast cancer risk in 6 population-based studies among up to 3,683 breast cancer cases and 34,174 controls in white women of European ancestry. In addition, we used these SNPs to calculate genetic risk scores (GRSs) based on their associations with each trait.

Results

After adjusting for age and potential population stratification, two age at menarche associated SNPs (rs1079866 and rs7821178) and one age at natural menopause associated SNP (rs2517388) were associated with breast cancer risk (p values, 0.003, 0.009 and 0.023, respectively). The odds ratios for breast cancer corresponding to per-risk-allele were 1.14 (95% CI, 1.05 to 1.24), 1.08 (95% CI, 1.02 to 1.15) and 1.10 (95% CI, 1.01 to 1.20), respectively, and were in the direction predicted by their associations with age at menarche or age at natural menopause. These associations did not appear to be attenuated by further controlling for self-reported age at menarche, age at natural menopause, or known breast cancer susceptibility loci. Although we did not observe a statistically significant association between any GRS for reproductive aging and breast cancer risk, the 4th and 5th highest quintiles of the younger age at menarche GRS had odds ratios of 1.14 (95% CI, 1.01 to 1.28) and 1.13 (95% CI, 1.00 to 1.27), respectively, compared to the lowest quintile.

Conclusions

Our study suggests that three genetic variants, independent of their associations with age at menarche or age at natural menopause, were associated with breast cancer risk and may contribute modestly to breast cancer risk prediction; however, the combination of the 19 age at menarche or the 17 age at natural menopause associated SNPs did not appear to be useful for identifying a high risk subgroup for breast cancer.
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Metadata
Title
Reproductive aging-associated common genetic variants and the risk of breast cancer
Authors
Chunyan He
Daniel I Chasman
Jill Dreyfus
Shih-Jen Hwang
Rikje Ruiter
Serena Sanna
Julie E Buring
Lindsay Fernández-Rhodes
Nora Franceschini
Susan E Hankinson
Albert Hofman
Kathryn L Lunetta
Giuseppe Palmieri
Eleonora Porcu
Fernando Rivadeneira
Lynda M Rose
Greta L Splansky
Lisette Stolk
André G Uitterlinden
Stephen J Chanock
Laura Crisponi
Ellen W Demerath
Joanne M Murabito
Paul M Ridker
Bruno H Stricker
David J Hunter
Publication date
01-04-2012
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 2/2012
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr3155

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