1. ¹Digestive Disease Research Center, Medical Sciences/University of Tehran, Tehran, Iran
2. ²Women's College Research Institute, University of Toronto, Toronto, Canada
3. ³Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Canada
4. ⁴Research Center of Gastroentrology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
5. ⁵International Agency for Research on Cancer, Lyon, France
6. ⁶Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
7. ⁷Epidemiology Research Unit Research Centre, CHUM- Hôtel-Dieu, University of Montreal, Montreal, Canada

Correspondence: Professor SA Narod, Women's College Research Institute, 7th Floor, 790 Bay Street, Toronto, Ontario M5G 1N8, Canada. E-mail: steven.narod@wchospital.ca; Professor R Malekzadeh, Digestive Disease Research Center, Shariati Hospital, Medical Sciences/University of Tehran, Tehran 14114, Iran. E-mail: malek@ams.ac.ir

Received 26 March 2007; Revised 13 June 2007; Accepted 13 July 2007; Published online 27 August 2007.

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%).