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The 3′ untranslated region C > T polymorphism of prohibitin is a breast cancer risk modifier in Polish women carrying a BRCA1 mutation

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Abstract

The variable penetrance of breast cancer in BRCA1 mutation carriers suggests that other genetic or environmental factors modify breast cancer risk. The C to T transition in the 3′ untranslated region of the prohibitin (PHB) gene alters mRNA function and has been shown to be associated with an increased breast cancer risk among young North-American women who have one first-degree relative with breast cancer. To investigate whether the PHB 3′UTR polymorphism acts as a modifier of hereditary breast cancer risk we performed a case-control study among female BRCA1 mutation carriers, which included 258 cases and 258 controls who were unaffected by ovarian cancer, in situ breast carcinoma or any other type of cancer. Controls were matched to cases by year of birth and BRCA1 mutation (5382insC, 300 T > G, 4153delA). Genotyping analysis was performed using RFLP-PCR. Odds ratios (OR) were calculated using conditional and penalised univariable and multivariable logistic regression. Multivariable penalised logistic regression revealed CT (ORadj, 2.03; 95% CI, 1.17–3.59) and combined CT + TT (ORadj, 2.12; 95% CI, 1.23–3.70) genotypes as significant modifiers of breast cancer risk. Breast cancer risk did not differ between carriers of the 300 T > G and 5382insC mutation. Our results suggest that the PHB 3′UTR T allele increases the risk of breast cancer in patients who are already at increased risk of disease.

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Acknowledgements

We are grateful to all women for their participation in this study. We thank Antje Seidel-Renkert and Michael Gilbert for expert technical assistance. This work was supported by the Deutsches Krebsforschungszentrum, Heidelberg. Anna Jakubowska is a guest researcher from the Pomeranian Medical University, Szczecin, Poland supported by a fellowship from the DKFZ. Jacek Gronwald was supported by a Yamagiwa-Yoshida Memorial UICC International Cancer Study Grant.

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Authors and Affiliations

  1. Department of Genetics and Pathology, Pomeranian Medical University, Ul. Polabska 4, 70-115, Szczecin, Poland

    Anna Jakubowska, Jacek Gronwald, Bohdan Górski, Tomasz Huzarski, Tomasz Byrski & Jan Lubiński

  2. Division of Molecular Genome Analysis, Molecular Genetics of Breast Cancer, German Cancer Research Center, Im Neuenheimer Feld 580, 69120, Heidelberg, Germany

    Anna Jakubowska & Ute Hamann

  3. Central Unit Biostatistics, German Cancer Research Center, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Axel Benner

  4. Discipline of Medical Genetics, School of Biomedical Sciences, University of Newcastle, and the Hunter Medical Research Institute, Lookout Road, New Lambton, 2305, NSW, Australia

    Rodney J. Scott

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  1. Anna Jakubowska
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  2. Jacek Gronwald
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Correspondence to Ute Hamann.

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Jakubowska, A., Gronwald, J., Górski, B. et al. The 3′ untranslated region C > T polymorphism of prohibitin is a breast cancer risk modifier in Polish women carrying a BRCA1 mutation. Breast Cancer Res Treat 104, 67–74 (2007). https://doi.org/10.1007/s10549-006-9389-3

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  • DOI: https://doi.org/10.1007/s10549-006-9389-3

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