Extremely High Tp53 Mutation Load in Esophageal Squamous Cell Carcinoma in Golestan Province, Iran

被引：27

作者：

Abedi-Ardekani, Behnoush ^{[1
,2
,3
]}

Kamangar, Farin ^{[4
,5
]}

Sotoudeh, Masoud ^{[1
]}

Villar, Stephanie ^{[2
]}

Islami, Farhad ^{[1
,2
,6
]}

Aghcheli, Karim ^{[1
]}

Nasrollahzadeh, Dariush ^{[1
,7
]}

Taghavi, Noushin ^{[1
]}

Dawsey, Sanford M. ^{[4
]}

Abnet, Christian C. ^{[4
]}

Hewitt, Stephen M. ^{[8
]}

Fahimi, Saman ^{[1
,9
]}

Saidi, Farrokh ^{[1
]}

Brennan, Paul ^{[2
]}

Boffetta, Paolo ^{[6
,10
]}

Malekzadeh, Reza ^{[1
]}

Hainaut, Pierre ^{[2
]}

机构：

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

[2] Int Agcy Res Canc, F-69372 Lyon, France

[3] Social Secur Org, Tehran, Iran

[4] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[5] Morgan State Univ, Sch Community Hlth & Policy, Dept Publ Hlth Anal, Baltimore, MD 21239 USA

[6] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA

[7] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[8] NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA

[9] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England

[10] Int Prevent Res Inst, Lyon, France

来源：

PLOS ONE | 2011年 / 6卷 / 12期

基金：

美国国家卫生研究院;

关键词：

POLYCYCLIC AROMATIC-HYDROCARBONS; HIGH-RISK AREA; NORTHEASTERN IRAN; DNA-DAMAGE; TOBACCO-SMOKE; NORTHERN IRAN; P53; MUTATIONS; CANCER; POPULATION; CHINA;

D O I：

10.1371/journal.pone.0029488

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Background: Golestan Province in northeastern Iran has one of the highest incidences of esophageal squamous cell carcinoma (ESCC) in the world with rates over 50 per 100,000 person-years in both sexes. We have analyzed TP53 mutation patterns in tumors from this high-risk geographic area in search of clues to the mutagenic processes involved in causing ESCC. Methodology/Principal Findings: Biopsies of 119 confirmed ESCC tumor tissue from subjects enrolled in a case-control study conducted in Golestan Province were analyzed by direct sequencing of TP53 exons 2 through 11. Immunohistochemical staining for p53 was carried out using two monoclonal antibodies, DO7 and 1801. A total of 120 TP53 mutations were detected in 107/119 cases (89.9%), including 11 patients with double or triple mutations. The mutation pattern was heterogeneous with infrequent mutations at common TP53 "hotspots" but frequent transversions potentially attributable to environmental carcinogens forming bulky DNA adducts, including 40% at bases known as site of mutagenesis by polycyclic aromatic hydrocarbons (PAHs). Mutations showed different patterns according to the reported temperature of tea consumption, but no variation was observed in relation to ethnicity, tobacco or opium use, and alcoholic beverage consumption or urban versus rural residence. Conclusion/Significance: ESCC tumors in people from Golestan Province show the highest rate of TP53 mutations ever reported in any cancer anywhere. The heterogeneous mutation pattern is highly suggestive of a causative role for multiple environmental carcinogens, including PAHs. The temperature and composition of tea may also influence mutagenesis.

引用

页数：9

共 38 条

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Polycyclic aromatic hydrocarbon exposure in oesophageal tissue and risk of oesophageal squamous cell carcinoma in north-eastern Iran [J].