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Published in: Breast Cancer Research and Treatment 2/2013

01-04-2013 | Epidemiology

Confirmation of the reduction of hormone replacement therapy-related breast cancer risk for carriers of the HSD17B1_937_G variant

Authors: Ofure Obazee, Christina Justenhoven, Stefan Winter, Jenny Chang-Claude, Anja Rudolph, Petra Seibold, Dieter Flesch-Janys, Ulf Hannelius, Jingmei Li, Keith Humphreys, Per Hall, Graham Giles, Gianluca Severi, Laura Baglietto, Melissa Southey, Sylvia Rabstein, Volker Harth, Anne Lotz, Beate Pesch, Thomas Brüning, Christian Baisch, Yon-Dschun Ko, Ute Hamann, Hiltrud Brauch

Published in: Breast Cancer Research and Treatment | Issue 2/2013

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Abstract

17β-hydroxysteroid dehydrogenase type 1 (HSD17B1) plays an important role in the biosynthesis of 17β-estradiol. The current study aimed at confirming the reduced risk of breast cancer in carriers of the non-synonymous HSD17B1_937_A>G (rs605059) polymorphism who used any hormone replacement therapy (HRT) for 10 years or longer. We performed an independent association study using four breast cancer case-control studies from Australia, Germany, and Sweden. In all, 5,777 cases and 8,189 age-matched controls of European descent were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and TaqMan. Risk estimates were calculated by interaction analysis and main effect analysis adjusted for age and study. Main effect analyses for women using any HRT for 10 years or longer (1,428 cases versus 1,724 controls) revealed a protective effect of the HSD17B1_937_G allele on breast cancer risk (OR 0.86, 95 % CI: 0.73–0.99; p = 0.048). Thus, our previous finding of a protective effect of the HSD17B1_937_G allele on HRT-associated breast cancer risk has now been confirmed both in independent large patient cohorts and a comprehensive pooled analysis supporting the hypothesis that a HSD17B1-mediated decreased conversion of estrone to the more potent 17β-estradiol may reduce the estrogenic effects, thereby reducing the risk of developing breast cancer during long-term HRT use.
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Metadata
Title
Confirmation of the reduction of hormone replacement therapy-related breast cancer risk for carriers of the HSD17B1_937_G variant
Authors
Ofure Obazee
Christina Justenhoven
Stefan Winter
Jenny Chang-Claude
Anja Rudolph
Petra Seibold
Dieter Flesch-Janys
Ulf Hannelius
Jingmei Li
Keith Humphreys
Per Hall
Graham Giles
Gianluca Severi
Laura Baglietto
Melissa Southey
Sylvia Rabstein
Volker Harth
Anne Lotz
Beate Pesch
Thomas Brüning
Christian Baisch
Yon-Dschun Ko
Ute Hamann
Hiltrud Brauch
Publication date
01-04-2013
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2013
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-013-2448-7

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