Article Type: Original Article
Abstract: Introduction: 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 for Fanconi anemia may be candidate genes for ESCC Method: We sequenced the entire coding regions of 12 Fanconi anemia genes in the germline DNAof 190 Turkmen ESCC cases Results: We identified three heterozygote insertion/deletions; 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. None of 811 Turkmen controls carried any of these three insertion/deletions. In addition, we found four homozygote carriers of the deleterious FANCA p.858Ser>Arg mutation in 746 ESCC patients, but in none of 1373 matched controls (P = 0.01). The p.3326Lys>X mutation in BRCA2 (Fanconi anemia gene FANCD1) was present in 27 of 746 ESCC cases and 16 of 1373 controls (OR=3.38; 95% CI: 1.97 - 6.91; P=0.0002). Conclusion: In summary, both heterozygote and homozygote mutations in a number of Fanconi anemia genes are associated with an increased risk of ESCC.