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A new polymorphism in the coding region of exon four in HSD17B2 in relation to risk of sporadic and hereditary breast cancer

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Abstract

In situ synthesis of oestrogens is of great importance in the development and progression of breast cancer. 17β-hydroxysteroid dehydrogenase (17HSD) type 2 catalyses oxidation from oestradiol to oestrone, and thereby protects the breast epithelial cells from oestradiol. Low expression of 17HSD type 2 has been associated with decreased survival in breast cancer, but no studies have investigated the mechanism behind the low expression. The 17HSD type 2 gene (HSD17B2) was screened for mutations with Single Stranded Conformation Polymorphism (SSCP)-DNA sequencing in 59 sporadic breast cancer cases, 19 hereditary breast cancer cases and seven breast cancer cell lines. DNA samples from 226 healthy individuals were used to identify if changes were previously unknown polymorphisms. No mutation was detected and therefore mutations in HSD17B2 do not explain why some breast tumours exhibit low 17HSD type 2 expression. However, a previously unknown polymorphism was found in exon four (Met226Val). Using molecular modelling, we found that the substituted residue is located at the outer part of the steroid binding site, probably causing minor alterations in the substrate binding. We further studied if the polymorphism contributes to breast cancer susceptibility in a larger material, but did not find an increased risk in the group of 317 sporadic breast cancer patients, 188 breast cancer patients with two close relatives with breast cancer or 122 hereditary breast cancer patients, compared to the healthy control group. We suggest that the detected polymorphism does not contribute to a higher risk of developing breast cancer.

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Abbreviations

17HSD:

17β-Hydroxysteroid dehydrogenase

ER:

Oestrogen receptor

Met:

Methionine

Val:

Valine

Gly:

Glycine

SSCP:

Single stranded conformation polymorphism

OR:

Odds ratio

CI:

Confidence interval

TCR:

Two close relatives with breast cancer

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Acknowledgements

This work was funded by the Swedish Cancer Society and Linköping University.

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Authors and Affiliations

  1. Department of Biomedicine and Surgery, Division of Oncology, Linköping University, 581 85, Linköping, Sweden

    Agneta Jansson, Anette Olsson, Petter Storm, Marie Stenmark-Askmalm & Olle Stål

  2. IFM Bioinformatics, Linköping University, 581 83, Linköping, Sweden

    Jonas Carlsson & Bengt Persson

  3. Department of Oncology, Karolinska University Hospital/Södersjukhuset, 118 83, Stockholm, Sweden

    Sara Margolin

  4. Division of Medical genetics, Linköping University, 581 85, Linköping, Sweden

    Cecilia Gunnarsson

  5. Department of Molecular Medicine, Karolinska Institute, 171 76, Stockholm, Sweden

    Annika Lindblom

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  1. Agneta Jansson
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Correspondence to Agneta Jansson.

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Jansson, A., Carlsson, J., Olsson, A. et al. A new polymorphism in the coding region of exon four in HSD17B2 in relation to risk of sporadic and hereditary breast cancer. Breast Cancer Res Treat 106, 57–64 (2007). https://doi.org/10.1007/s10549-006-9477-4

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  • DOI: https://doi.org/10.1007/s10549-006-9477-4

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