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International Journal of Colorectal Disease

, Volume 26, Issue 4, pp 455–467 | Cite as

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

  • Sana Aissi-Ben Moussa
  • Amel Moussa
  • Nadia Kourda
  • Amel Mezlini
  • Nabil Abdelli
  • Farid Zerimech
  • Taoufik Najjar
  • Sarah Ben Jilani
  • Nicole Porchet
  • Farhat Ben Ayed
  • Mohamed Manai
  • Marie-Pierre BuisineEmail author
Original Article

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.

Keywords

Lynch syndrome Hereditary nonpolyposis colorectal cancer DNA mismatch repair Microsatellite instability MUTYH 

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

Notes

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

None.

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Sana Aissi-Ben Moussa
    • 1
    • 2
  • Amel Moussa
    • 3
  • Nadia Kourda
    • 4
  • Amel Mezlini
    • 5
  • Nabil Abdelli
    • 6
  • Farid Zerimech
    • 7
  • Taoufik Najjar
    • 3
  • Sarah Ben Jilani
    • 4
  • Nicole Porchet
    • 2
    • 7
    • 8
  • Farhat Ben Ayed
    • 5
  • Mohamed Manai
    • 1
  • Marie-Pierre Buisine
    • 2
    • 7
    • 8
    • 9
    Email author
  1. 1.Laboratoire de Biochimie et Biologie Moléculaire de la Faculté des Sciences de TunisTunisTunisia
  2. 2.Inserm, U837, Centre de Recherche JP Aubert, Equipe n°5Lille, and Cancéropôle Nord-OuestLilleFrance
  3. 3.Service de Gastro-EntérologieHôpital Charles Nicolle de TunisTunisTunisia
  4. 4.Laboratoire d’AnatomopathologieHôpital Charles Nicolle de TunisTunisTunisia
  5. 5.Service d’Oncologie MédicaleInstitut de Carcinologie Salah Azaiez de TunisTunisTunisia
  6. 6.Service de Gastro-EntérologieHôpital Militaire de TunisTunisTunisia
  7. 7.Laboratoire de Biochimie et Biologie MoléculaireCHRU de LilleLilleFrance
  8. 8.Faculté de Médecine H. WarembourgUniversité de Lille Nord de FranceLilleFrance
  9. 9.Oncologie et Génétique Moléculaires, Laboratoire de Biochimie et Biologie Moléculaire, Centre de Biologie-PathologieCHRU de LilleLille CedexFrance

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