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Breast Cancer Research and Treatment

, Volume 138, Issue 2, pp 543–548 | Cite as

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

  • 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 BrauchEmail author
Epidemiology

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.

Keywords

HSD17B1 Polymorphism Breast cancer risk Hormone replacement therapy 

Notes

Acknowledgments

The authors acknowledge support of the Robert Bosch Foundation, Stuttgart, Germany, and the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114. OO was supported by the 7FP EU Marie Curie Initial Training Network “FightingDrugFailure” (GA238132). The MARIE study was supported by the Deutsche Krebshilfe e.V., grant number 70-2892-BR I and the Hamburg Cancer Society. The MARIE-GENICA project was funded by BMBF Germany grants 01KH0401, 01KH0402, 01KH0410, and 01KH0411. SASBAC was supported by National Institutes of Health (RO1 CA58427) and Märit and Hans Rausing’s Initiative Against Breast Cancer. KC was supported by the Swedish Cancer Society (5128-B07-01PAF). MCCS is supported by Cancer Council Victoria and by NHMRC (grants 209057, 251533, 396414, 504711, and 504715).

Conflict of interest

The authors have no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Ofure Obazee
    • 1
    • 13
  • Christina Justenhoven
    • 1
    • 13
  • Stefan Winter
    • 1
    • 13
  • Jenny Chang-Claude
    • 2
  • Anja Rudolph
    • 2
  • Petra Seibold
    • 2
  • Dieter Flesch-Janys
    • 3
  • Ulf Hannelius
    • 4
  • Jingmei Li
    • 4
    • 5
  • Keith Humphreys
    • 4
  • Per Hall
    • 4
  • Graham Giles
    • 6
    • 7
  • Gianluca Severi
    • 6
    • 7
  • Laura Baglietto
    • 6
    • 7
  • Melissa Southey
    • 8
  • Sylvia Rabstein
    • 9
  • Volker Harth
    • 9
    • 10
  • Anne Lotz
    • 9
  • Beate Pesch
    • 9
  • Thomas Brüning
    • 9
  • Christian Baisch
    • 11
  • Yon-Dschun Ko
    • 11
  • Ute Hamann
    • 12
  • Hiltrud Brauch
    • 1
    • 13
    Email author
  1. 1.Dr. Margarete Fischer-Bosch-Institute of Clinical PharmacologyStuttgartGermany
  2. 2.Divison of Cancer EpidemiologyGerman Cancer Research Center (DKFZ)HeidelbergGermany
  3. 3.Department of Medical Biometry and EpidemiologyCenter for Experimental Medicine, University Medical Center Hamburg-EppendorfHamburgGermany
  4. 4.Department of Medical Epidemiology and BiostatisticsKarolinska InstituteStockholmSweden
  5. 5.Human Genetics, Genome Institute of SingaporeSingaporeSingapore
  6. 6.Cancer Epidemiology Centre, The Cancer Council VictoriaMelbourneAustralia
  7. 7.Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of MelbourneMelbourneAustralia
  8. 8.Genetic Epidemiology Laboratory, Department of PathologyThe University of MelbourneMelbourneAustralia
  9. 9.Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum (IPA)BochumGermany
  10. 10.Institute for Occupational Medicine and Maritime MedicineUniversity Medical Center Hamburg-EppendorfHamburgGermany
  11. 11.Department of Internal MedicineEvangelische Kliniken Bonn gGmbH, Johanniter KrankenhausBonnGermany
  12. 12.Molecular Genetics of Breast CancerDeutsches Krebsforschungszentrum (DKFZ)HeidelbergGermany
  13. 13.University of TübingenTübingenGermany

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