title: Confirmation of the reduction of hormone replacement therapy-related breast cancer risk for carriers of the HSD17B1_937_G variant.
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.
authors: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Auerbachstrasse 112, 70376, Stuttgart, Germany.
authors: Ofure
authors: O
authors: Obazee
authors: Christina
authors: C
authors: Justenhoven
authors: Stefan
authors: S
authors: Winter
authors: Jenny
authors: J
authors: Chang-Claude
authors: Anja
authors: A
authors: Rudolph
authors: Petra
authors: P
authors: Seibold
authors: Dieter
authors: D
authors: Flesch-Janys
authors: Ulf
authors: U
authors: Hannelius
authors: Jingmei
authors: J
authors: Li
authors: Keith
authors: K
authors: Humphreys
authors: Per
authors: P
authors: Hall
authors: Graham
authors: G
authors: Giles
authors: Gianluca
authors: G
authors: Severi
authors: Laura
authors: L
authors: Baglietto
authors: Melissa
authors: M
authors: Southey
authors: Sylvia
authors: S
authors: Rabstein
authors: Volker
authors: V
authors: Harth
authors: Anne
authors: A
authors: Lotz
authors: Beate
authors: B
authors: Pesch
authors: Thomas
authors: T
authors: Brüning
authors: Christian
authors: C
authors: Baisch
authors: Yon-Dschun
authors: YD
authors: Ko
authors: Ute
authors: U
authors: Hamann
authors: Hiltrud
authors: H
authors: Brauch
mesh_terms: D001943:Breast Neoplasms / Q000139:chemically induced / Q000235:genetics*; D016022:Case-Control Studies; D004960:Estradiol Dehydrogenases / Q000235:genetics*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D012307:Risk Factors
chemical_list: D004960:Estradiol Dehydrogenases; C513331:HSD17B1 protein, human