Mutations in Fanconi anemia genes and the risk of esophageal cancer

被引：44

作者：

Akbari, Mohammad R. ^{[1
,2
,3
]}

Malekzadeh, Reza ^{[1
]}

Lepage, Pierre ^{[4
]}

Roquis, David ^{[4
]}

Sadjadi, Ali R. ^{[1
]}

Aghcheli, Karim ^{[1
]}

Yazdanbod, Abbas ^{[5
]}

Shakeri, Ramin ^{[1
]}

Bashiri, Jafar ^{[1
]}

Sotoudeh, Masoud ^{[1
]}

Pourshams, Akram ^{[1
]}

Ghadirian, Parviz ^{[6
]}

Narod, Steven A. ^{[2
]}

机构：

[1] Univ Tehran Med Sci, Digest Dis Res Ctr, Shariati Hosp, Tehran 14114, Iran

[2] Univ Toronto, Womens Coll Res Inst, Toronto, ON M5G 1N8, Canada

[3] Univ Toronto, Inst Med Sci, Fac Med, Toronto, ON M5S 1A1, Canada

[4] McGill Univ, Genome Quebec Innovat Ctr, Montreal, PQ, Canada

[5] Ardabil Univ Med Sci, Dept Internal Med, Ardebil, Iran

[6] Univ Montreal, Epidemiol Res Unit, Res Ctr, CHUM Hotel Dieu, Montreal, PQ, Canada

来源：

HUMAN GENETICS | 2011年 / 129卷 / 05期

基金：

加拿大健康研究院;

关键词：

POLYMORPHIC STOP CODON; FANCD2; SUSCEPTIBILITY; IDENTIFICATION; BRCA2; PATHWAY; PROTEIN; POPULATION; INSIGHTS; DELETION;

D O I：

10.1007/s00439-011-0951-7

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：573 / 582

页数：10

共 55 条

[1] Heterogeneous activation of the Fanconi anemia pathway by patient-derived FANCA mutants [J].