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Family history predictors of BRCA1/BRCA2 mutation status among Tunisian breast/ovarian cancer families

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Abstract

Background

With the increasing request for BRCA1/BRCA2 mutation tests, several risk models have been developed to predict the presence of mutation in these genes; in this study, we have developed an efficient BRCA genetic testing strategy.

Method

As first step, to identify predictor variables associated with BRCA status, we have undertaken a cumulative mutation analysis including data from three Tunisian studies. Then, we have developed a logistic regression model for predicting the likelihood of harboring a BRCA mutation. Using receiver operating characteristic curves (ROC), an effective evaluation was performed. A total of 92 Tunisian families were included. Overall, 27 women were positive for BRCA1/BRCA2 deleterious mutations.

Results

Tow recurrent mutations (c.211dupA and c.5266dupC) explained 76 % of BRCA1-related families and three recurrent mutations (c.1310_1313del, c.1542_1547delAAGA and c.7887_7888insA) explained 90 % of BRCA2-related families. Early age at diagnosis of breast cancer, ovarian cancer, bilateral breast cancer were associated with BRCA1, whereas male breast cancer and four or more breast cancer cases in the family were associated with BRCA2. The area under the receiver operating characteristic curve of the risk score was 0.802 (95 % confidence interval = 0.0699–0. 905).

Conclusion

Logistic regression reported particular profiles related to BRCA germline mutation carriers in our population, as well as an efficient prediction model that may be a useful tool for increasing the cost-effectiveness of genetic testing strategy.

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Acknowledgments

The authors thank all the clinicians at the Salah Azaiz Cancer Institute for taking part in this study.

Author information

Authors and Affiliations

  1. Laboratoire Génétique Humaine, Faculté de Médecine de Tunis, University Tunis El Manar, 3, Rue ALI DOUAGI, Bardo, Tunis, Tunisia

    Aouatef Riahi

  2. High School of Economic and Commercial Sciences of Tunis, University of Tunis, Tunis, Tunisia

    Mohamel el Ghourabi

  3. Department of Immunohistocytology, Salah Azaiz Institute, Tunis, Tunisia

    Asma Fourati

  4. Department of Hereditary and Congenital Disorders, Charles Nicolle Hospital, Tunis, Tunisia

    Habiba Chaabouni-Bouhamed

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  1. Aouatef Riahi
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  2. Mohamel el Ghourabi
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  3. Asma Fourati
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  4. Habiba Chaabouni-Bouhamed
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Corresponding author

Correspondence to Aouatef Riahi.

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Funding sources

This work was funded by the Ministry of High Education and Scientific Research and Technology (Tunisia).

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The authors made no disclosures.

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Riahi, A., Ghourabi, M.e., Fourati, A. et al. Family history predictors of BRCA1/BRCA2 mutation status among Tunisian breast/ovarian cancer families. Breast Cancer 24, 238–244 (2017). https://doi.org/10.1007/s12282-016-0693-4

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  • DOI: https://doi.org/10.1007/s12282-016-0693-4

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