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Lynch syndrome in Tunisia: first description of clinical features and germline mutations

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

High rates of early colorectal cancers (CRC) are observed in Tunisia suggesting genetic susceptibility. Nevertheless, up to now, no molecular study has been performed in the Tunisian population. In our research, we evaluated the clinical characteristics of Tunisian families suspected of Lynch syndrome and the contribution of DNA mismatch repair (MMR) genes.

Methods

Thirty-one unrelated families suspected of Lynch syndrome were studied. Probands were tested for the presence of germline mutations in the MMR genes MLH1, MSH2, MSH6 and in MUTYH. Available tumours were analysed for microsatellite instability and expression of MMR proteins. Detailed family and medical histories were collected.

Results

A total of 134 cancers were noted in the 31 families, the most frequent type of cancer corresponding to CRC (69%), followed by uterine cancer (7.5%). Germline mutations were identified in 11 (35.5%) families (six MSH2, five MLH1, including seven novel mutations), seven of which fulfilled the Amsterdam criteria (sensitivity, 63.6%; positive predictive value, 58.3%). Noteworthy, germline mutations were detected in 52.6% of male patients tested, but in only 8.3% of females (p = 0.02). Moreover, CRC were essentially left sided in families without detected mutation (p = 0.017). Ages of onset of cancers and tumour spectrum were very similar in families with or without MMR germline mutation, contrasting with previous studies performed in other populations.

Conclusions

MMR genes contribute significantly to CRC susceptibility in the Tunisian population. However, the cause of early CRC susceptibility remains unknown in most cases, especially in women and in patients with early left colon or rectal cancer.

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Abbreviations

CRC:

Colorectal cancer

HNPCC:

Hereditary nonpolyposis colorectal cancer

MLPA:

Multiplex ligation dependent probe amplification

MMR:

Mismatch repair

MSI:

Microsatellite instability

MSI-H:

Microsatellite instability-high

MSS:

Microsatellite stable

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Acknowledgements

This study was the result of collaboration between the Universities of Tunis-El Manar and Lille Nord de France. S.A.B. was supported in part by a grant from the Tunisian government. We are indebted to all family members who agreed to attend our study. We also thank Dr O. Trabelsi, gastroenterologist in Tunis, Tunisia for providing us with families, Dr A. Wacrenier, Department of Pathology of the CHRU of Lille, France, for her help in immunohistochemistry of MMR proteins, Dr M. Crépin, Platform of Molecular Biology of the CHRU of Lille, France, and S. Aissi for revision of the text.

Conflict of interest

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Authors and Affiliations

  1. Laboratoire de Biochimie et Biologie Moléculaire de la Faculté des Sciences de Tunis, Tunis, Tunisia

    Sana Aissi-Ben Moussa & Mohamed Manai

  2. Inserm, U837, Centre de Recherche JP Aubert, Equipe n°5, Lille, and Cancéropôle Nord-Ouest, Lille, France

    Sana Aissi-Ben Moussa, Nicole Porchet & Marie-Pierre Buisine

  3. Service de Gastro-Entérologie, Hôpital Charles Nicolle de Tunis, Tunis, Tunisia

    Amel Moussa & Taoufik Najjar

  4. Laboratoire d’Anatomopathologie, Hôpital Charles Nicolle de Tunis, Tunis, Tunisia

    Nadia Kourda & Sarah Ben Jilani

  5. Service d’Oncologie Médicale, Institut de Carcinologie Salah Azaiez de Tunis, Tunis, Tunisia

    Amel Mezlini & Farhat Ben Ayed

  6. Service de Gastro-Entérologie, Hôpital Militaire de Tunis, Tunis, Tunisia

    Nabil Abdelli

  7. Laboratoire de Biochimie et Biologie Moléculaire, CHRU de Lille, Lille, France

    Farid Zerimech, Nicole Porchet & Marie-Pierre Buisine

  8. Faculté de Médecine H. Warembourg, Université de Lille Nord de France, Lille, France

    Nicole Porchet & Marie-Pierre Buisine

  9. Oncologie et Génétique Moléculaires, Laboratoire de Biochimie et Biologie Moléculaire, Centre de Biologie-Pathologie, CHRU de Lille, 59037, Lille Cedex, France

    Marie-Pierre Buisine

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  1. Sana Aissi-Ben Moussa
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  2. Amel Moussa
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  3. Nadia Kourda
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  4. Amel Mezlini
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  5. Nabil Abdelli
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  6. Farid Zerimech
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  7. Taoufik Najjar
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  8. Sarah Ben Jilani
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  9. Nicole Porchet
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  10. Farhat Ben Ayed
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  11. Mohamed Manai
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  12. Marie-Pierre Buisine
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Correspondence to Marie-Pierre Buisine.

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Moussa, S.AB., Moussa, A., Kourda, N. et al. Lynch syndrome in Tunisia: first description of clinical features and germline mutations. Int J Colorectal Dis 26, 455–467 (2011). https://doi.org/10.1007/s00384-010-1129-9

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