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Germline BRCA2 mutations and the risk of esophageal squamous cell carcinoma

Oncogene volume 27, pages 1290–1296 (2008)Cite this article

Abstract

The incidence of esophageal squamous cell carcinoma (ESCC) is very high among the Turkmen population of Iran. Family studies suggest a genetic component to the disease. Turkmen are ethnically homogenous and are well suited for genetic studies. A previous study from China suggested that BRCA2 might play a role in the etiology of ESCC. We screened for mutations in the coding region of the BRCA2 gene in the germline DNA of 197 Turkmen patients with ESCC. A nonsense variant, K3326X, was identified in 9 of 197 cases (4.6%) vs 2 of 254 controls (0.8%) (OR=6.0, 95% CI=1.3–28; P=0.01). This mutation leads to the loss of the C-terminal domain of the BRCA2 protein, a part of the region of interaction with the FANCD2 protein. We observed nine other BRCA2 variants in single cases only, including two deletions, and seven missense mutations. Six of these were judged to be pathogenic. In total, a suspicious deleterious BRCA2 variant was identified in 15 of 197 ESCC cases (7.6%).

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Acknowledgements

We thank Dr Haj-amin Marjani, Dr Noushin Taghavi and Dr Fatemeh Rajabzadeh from the case–control study center (Atrak Clinic) in Gonbad city for helping with study subject recruitment. We also appreciate the kind help of Ofelia Francisco-Pabalan, Cheryl Crozier and Swan Cot for laboratory testings. This study was supported by grants from the Canadian Institutes of Health Research (CIHR) and the Digestive Disease Research Center (DDRC), Tehran University of Medical Sciences (TUMS).

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Authors and Affiliations

  1. Digestive Disease Research Center, Medical Sciences/University of Tehran, Tehran, Iran

    M R Akbari, R Malekzadeh, D Nasrollahzadeh, D Amanian, F Islami, R Shakeri, M Sotoudeh, K Aghcheli & A Pourshams

  2. Women's College Research Institute, University of Toronto, Toronto, Canada

    M R Akbari, S Li, I Zandvakili & S A Narod

  3. Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Canada

    M R Akbari

  4. Research Center of Gastroentrology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran

    R Salahi & S Semnani

  5. International Agency for Research on Cancer, Lyon, France

    P Boffetta

  6. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA

    S M Dawsey

  7. Epidemiology Research Unit Research Centre, CHUM- Hôtel-Dieu, University of Montreal, Montreal, Canada

    P Ghadirian

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Correspondence to R Malekzadeh or S A Narod.

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Akbari, M., Malekzadeh, R., Nasrollahzadeh, D. et al. Germline BRCA2 mutations and the risk of esophageal squamous cell carcinoma. Oncogene 27, 1290–1296 (2008). https://doi.org/10.1038/sj.onc.1210739

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