title: Mutations in Fanconi anemia genes and the risk of esophageal cancer.
abstract: The incidence of esophageal squamous cell carcinoma (ESCC) is very high in northeastern Iran. Previously, we reported a strong familial component of ESCC among Turkmens, who constitute approximately one-half of the population of this region. We hypothesized that the genes which cause Fanconi anemia might be candidate genes for ESCC. We sequenced the entire coding regions of 12 Fanconi anemia genes in the germline DNA of 190 Turkmen cases of ESCC. We identified three heterozygous insertion/deletion mutations: one in FANCD2 (p.Val1233del), one in FANCE (p.Val311SerfsX2), and one in FANCL (p.Thr367AsnfsX13). All three patients had a strong family history of ESCC. In addition, four patients (out of 746 tested) were homozygous for the FANCA p.Ser858Arg mutation, compared to none of 1,373 matched controls (OR = 16.7, 95% CI = 6.2-44.2, P = 0.01). The p. Lys3326X mutation in BRCA2 (also known as Fanconi anemia gene FANCD1) was present in 27 of 746 ESCC cases and in 16 of 1,373 controls (OR = 3.38, 95% CI = 1.97-6.91, P = 0.0002). In summary, both heterozygous and homozygous mutations in several Fanconi anemia-predisposing genes are associated with an increased risk of ESCC in Iran.
authors.affiliation: Digestive Disease Research Center, Shariati Hospital, Tehran University of Medical Sciences, North Kargar Street, Tehran, Iran.
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Akbari
authors.forename: Reza
authors.initials: R
authors.lastname: Malekzadeh
authors.forename: Pierre
authors.initials: P
authors.lastname: Lepage
authors.forename: David
authors.initials: D
authors.lastname: Roquis
authors.forename: Ali R
authors.initials: AR
authors.lastname: Sadjadi
authors.forename: Karim
authors.initials: K
authors.lastname: Aghcheli
authors.forename: Abbas
authors.initials: A
authors.lastname: Yazdanbod
authors.forename: Ramin
authors.initials: R
authors.lastname: Shakeri
authors.forename: Jafar
authors.initials: J
authors.lastname: Bashiri
authors.forename: Masoud
authors.initials: M
authors.lastname: Sotoudeh
authors.forename: Akram
authors.initials: A
authors.lastname: Pourshams
authors.forename: Parviz
authors.initials: P
authors.lastname: Ghadirian
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics*; D005199:Fanconi Anemia / Q000235:genetics*; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000235:genetics; D052239:Fanconi Anemia Complementation Group E Protein / Q000235:genetics; D052240:Fanconi Anemia Complementation Group L Protein / Q000235:genetics; D005260:Female; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006801:Humans; D054643:INDEL Mutation; D007492:Iran / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D012306:Risk
chemical_list: C499907:FANCE protein, human; D052236:Fanconi Anemia Complementation Group D2 Protein; D052239:Fanconi Anemia Complementation Group E Protein; D052240:Fanconi Anemia Complementation Group L Protein