Analysis of 17β-hydroxysteroid dehydrogenase types 5, 7, and 12 genetic sequence variants in breast cancer cases from French Canadian Families with high risk of breast and ovarian cancer

Plourde, Marie; Ferland, Alexandra; Soucy, Penny; Hamdi, Yosr; Tranchant, Martine; Durocher, Francine; Simard, Jacques

doi:10.1016/j.jsbmb.2009.05.005

Cited by 12 publications

(6 citation statements)

References 76 publications

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“…In line with our null results, no genetic main effects have previously been detected for the investigated SNPs in SRD5A1, SRD5A2, and AKR1C3 in relation to breast cancer [23,43] as well as for AKR1C4_rs3750572 (r 2 = 1.00 with AKR1C4_rs3829125 and AKR1C4_17134592) on mammographic density [44].…”

Section: Discussionsupporting

confidence: 90%

Polymorphism Thr160Thr in SRD5A1, involved in the progesterone metabolism, modifies postmenopausal breast cancer risk associated with menopausal hormone therapy

Hein

Abbas

Seibold

et al. 2011

Breast Cancer Res Treat

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Menopausal hormone therapy (MHT) is associated with an increased breast cancer risk in postmenopausal women, with combined estrogen-progestagen therapy posing a greater risk than estrogen monotherapy. However, few studies focused on potential effect modification of MHT-associated breast cancer risk by genetic polymorphisms in the progesterone metabolism. We assessed effect modification of MHT use by five coding single nucleotide polymorphisms (SNPs) in the progesterone metabolizing enzymes AKR1C3 (rs7741), AKR1C4 (rs3829125, rs17134592), and SRD5A1 (rs248793, rs3736316) using a two-center population-based case-control study from Germany with 2,502 postmenopausal breast cancer patients and 4,833 matched controls. An empirical-Bayes procedure that tests for interaction using a weighted combination of the prospective and the retrospective case-control estimators as well as standard prospective logistic regression were applied to assess multiplicative statistical interaction between polymorphisms and duration of MHT use with regard to breast cancer risk assuming a log-additive mode of inheritance. No genetic marginal effects were observed. Breast cancer risk associated with duration of combined therapy was significantly modified by SRD5A1_rs3736316, showing a reduced risk elevation in carriers of the minor allele (p (interaction,empirical-Bayes) = 0.006 using the empirical-Bayes method, p (interaction,logistic regression) = 0.013 using logistic regression). The risk associated with duration of use of monotherapy was increased by AKR1C3_rs7741 in minor allele carriers (p (interaction,empirical-Bayes) = 0.083, p (interaction,logistic regression) = 0.029) and decreased in minor allele carriers of two SNPs in AKR1C4 (rs3829125: p (interaction,empirical-Bayes) = 0.07, p (interaction,logistic regression) = 0.021; rs17134592: p (interaction,empirical-Bayes) = 0.101, p (interaction,logistic regression) = 0.038). After Bonferroni correction for multiple testing only SRD5A1_rs3736316 assessed using the empirical-Bayes method remained significant. Postmenopausal breast cancer risk associated with combined therapy may be modified by genetic variation in SRD5A1. Further well-powered studies are, however, required to replicate our finding.

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Section: Discussionsupporting

confidence: 90%

Polymorphism Thr160Thr in SRD5A1, involved in the progesterone metabolism, modifies postmenopausal breast cancer risk associated with menopausal hormone therapy

Hein

Abbas

Seibold

et al. 2011

Breast Cancer Res Treat

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“…17β-HSD-1, 5, 7, and 12; the individual isoforms that can metabolize androstenediol to androstenedione, are expressed in epithelial cells of acini and/or ducts as well as in the stromal cells in the breast [25]. Human 17β-HSD-5 belongs to the aldo-keto reductase (AKR) superfamily [26] is identical to AKR1C3 [27]. It is widely expressed in human tissues including the prostate, endometrium, and mammary gland [28].…”

Section: Enzymology Of Estrogen Biosynthesis In Postmenopausal Womenmentioning

confidence: 99%

“…It is widely expressed in human tissues including the prostate, endometrium, and mammary gland [28]. AKR1C3 as well as 17β-HSD-1, 7, and 12 are all expressed in breast tumor tissue [26,29]. Aromatase (CYP19), which converts androstenedione to estrone and testosterone to estradiol, is expressed in stromal and carcinoma or parenchymal components of breast cancer tissue [30].…”

Section: Enzymology Of Estrogen Biosynthesis In Postmenopausal Womenmentioning

confidence: 99%

Analysis of estrogens in serum and plasma from postmenopausal women: Past present, and future

Blair

2010

Steroids

113

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Previous studies have shown that the selection of women who are at high breast cancer risk for treatment with chemoprevention agents leads to an enhanced benefit/risk ratio. However, further efforts to implement this strategy will require the development of new models to predict the breast cancer risk of particular individuals. Postmenopausal women with elevated plasma or serum estrogens are at increased risk for breast cancer. Therefore, the roles of various enzymes involved in the biosynthesis of estrogens in postmenopausal women have been reviewed in detail. In addition, the potential genotoxic and/or proliferative effects of the different estrogen metabolites as risk factors in the etiology of breast cancer have been examined. Unfortunately, much of the current bioanalytical methodology employed for the analysis of plasma and serum estrogens has proved to be problematic. Major advances in risk assessment would be possible if reliable methodology were available to quantify estradiol and its major metabolites in the plasma or serum of postmenopausal women. High performance liquid chromatography (HPLC) coupled with radioimmunoassay (RIA) currently provides the most sensitive and best validated immunoassay method for the analysis for estrone and estradiol in serum samples from postmenopausal women. However, inter-individual differences in specificity observed with many other immunoassays have caused significant problems when interpreting epidemiologic studies of breast cancer. It is almost impossible to overcome the inherent assay problems involved in using RIA-based methodology, particularly for multiple estrogens. For reliable measurements of multiple estrogens in plasma or serum, it will be necessary to employ stable isotope dilution methodology in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) Extremely high sensitivity can be obtained with pre-ionized estrogen derivatives when employed in combination with a modern triple quadrupole mass spectrometer and nanoflow LC. Using [ 13 C 6 ]-estrone as the internal standard it has proved possible to analyze estrone as its preionized Girard T (GT) derivative in sub-fg (low amol) amounts on column. This suggests that in the future it will be possible to routinely conduct LC-MS assays of multiple estrogen metabolites in serum and plasma at even lower concentrations than the current lower limit of quantitation of 0.4 pg/ mL (1.6 pmol/L). The ease with which the pre-ionization derivatization strategy can be implemented will make it possible to readily introduce high sensitivity stable isotope dilution methodology in laboratories that are currently employing LC-MS/MS methodology. This will help conserve important plasma and serum samples as it will be possible to conduct high sensitivity analyses using low sample volumes.

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“…HSD17B12 has been identified as an oncogene in various cancers. Studies have shown that HSD17B12 mRNA expression level is higher in breast tumour tissues than in normal tissues and negatively correlated with prognosis 38,39 . HSD17B12 is also gradually up‐regulated with the severity of ovarian cancer 40 .…”

Section: Discussionmentioning

confidence: 99%

Functional genetic variant of HSD17B12 in the fatty acid biosynthesis pathway predicts the outcome of colorectal cancer

Lin

Meng

Zhang

et al. 2020

J Cellular Molecular Medi

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Analysis of 17β-hydroxysteroid dehydrogenase types 5, 7, and 12 genetic sequence variants in breast cancer cases from French Canadian Families with high risk of breast and ovarian cancer

Cited by 12 publications

References 76 publications

Polymorphism Thr160Thr in SRD5A1, involved in the progesterone metabolism, modifies postmenopausal breast cancer risk associated with menopausal hormone therapy

Polymorphism Thr160Thr in SRD5A1, involved in the progesterone metabolism, modifies postmenopausal breast cancer risk associated with menopausal hormone therapy

Analysis of estrogens in serum and plasma from postmenopausal women: Past present, and future

Functional genetic variant of HSD17B12 in the fatty acid biosynthesis pathway predicts the outcome of colorectal cancer

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