title: Germline BRCA2 mutations and the risk of esophageal squamous cell carcinoma.
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%).
authors.affiliation: Digestive Disease Research Center, Medical Sciences/University of Tehran, Tehran, Iran.
authors.forename: M R
authors.initials: MR
authors.lastname: Akbari
authors.forename: R
authors.initials: R
authors.lastname: Malekzadeh
authors.forename: D
authors.initials: D
authors.lastname: Nasrollahzadeh
authors.forename: D
authors.initials: D
authors.lastname: Amanian
authors.forename: F
authors.initials: F
authors.lastname: Islami
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.forename: I
authors.initials: I
authors.lastname: Zandvakili
authors.forename: R
authors.initials: R
authors.lastname: Shakeri
authors.forename: M
authors.initials: M
authors.lastname: Sotoudeh
authors.forename: K
authors.initials: K
authors.lastname: Aghcheli
authors.forename: R
authors.initials: R
authors.lastname: Salahi
authors.forename: A
authors.initials: A
authors.lastname: Pourshams
authors.forename: S
authors.initials: S
authors.lastname: Semnani
authors.forename: P
authors.initials: P
authors.lastname: Boffetta
authors.forename: S M
authors.initials: SM
authors.lastname: Dawsey
authors.forename: P
authors.initials: P
authors.lastname: Ghadirian
authors.forename: S A
authors.initials: SA
authors.lastname: Narod
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D018389:Codon, Nonsense / Q000235:genetics; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007492:Iran / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics
chemical_list: D024682:BRCA2 Protein; D018389:Codon, Nonsense