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Extremely high Tp53 mutation load in esophageal squamous cell carcinoma in Golestan Province, Iran

Abedi-Ardekani, B. and Kamangar, F. and Sotoudeh, M. and Villar, S. and Islami, F. and Aghcheli, K. and Nasrollahzadeh, D. and Taghavi, N. and Dawsey, S.M. and Abnet, C.C. and Hewitt, S.M. and Fahimi, S. and Saidi, F. and Brennan, P. and Boffetta, P. and Malekzadeh, R. and Hainaut, P. (2011) Extremely high Tp53 mutation load in esophageal squamous cell carcinoma in Golestan Province, Iran. PLoS ONE, 6 (12).

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Abstract

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.

Item Type: Article
Additional Information: cited By 10
Uncontrolled Keywords: DNA; monoclonal antibody; opiate; polycyclic aromatic hydrocarbon; protein p53, adult; aged; alcohol consumption; article; cigarette smoking; controlled study; DNA adduct; esophagus biopsy; esophagus carcinoma; ethnicity; exon; female; fluid intake; gene mutation; human; human cell; human tissue; immunohistochemistry; Iran; major clinical study; male; mutagenesis; sequence analysis; squamous cell carcinoma; tea; tumor suppressor gene; urban rural difference; water temperature; codon; esophagus tumor; genetics; Iran; mutation; risk factor; squamous cell carcinoma, Aged; Carcinoma, Squamous Cell; Codon; Esophageal Neoplasms; Female; Genes, p53; Humans; Iran; Male; Mutation; Risk Factors
Subjects: کهورت
مقالات نمایه شده محققین دانشگاه در سایت ,Web of Science ,Scopus
موارد کلی
Divisions: معاونت تحقیقات و فناوری
Depositing User: GOUMS
Date Deposited: 20 Apr 2015 04:10
Last Modified: 12 Mar 2016 06:55
URI: http://eprints.goums.ac.ir/id/eprint/2552

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