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.