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Urothelial carcinomas arising in arsenic‐contaminated areas are associated with hypermethylation of the gene promoter of the death‐associated protein kinase
Author(s) -
Chen WT,
Hung WC,
Kang WY,
Huang YC,
Chai CY
Publication year - 2007
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/j.1365-2559.2007.02871.x
Subject(s) - arsenic , methylation , dna methylation , cancer research , immunohistochemistry , carcinogenesis , medicine , carcinoma , biology , pathology , gene , cancer , gene expression , chemistry , genetics , organic chemistry
Aims: The mechanisms of urothelial carcinogenesis in areas highly contaminated with arsenic remain unclear. The aim was to determine whether hypermethylation of death‐associated protein kinase (DAPK) gene is associated with chronic arsenic exposure. Methods and results: The frequency of aberrant promoter methylation of DAPK in 17 urothelial carcinomas from an arsenic‐contaminated area and 21 urothelial carcinomas from a non‐arsenic‐contaminated area was determined by methylation‐specific polymerase chain reaction. DAPK hypermethylation status was significantly higher in urothelial cancers arising in arsenic‐contaminated areas when compared with tumours from patients from non‐contaminated areas ( P = 0.018). In the subset of patients from living environments which were contaminated with arsenic, there was a statistically significant association between DAPK hypermethylation and patient’s age, tumour invasiveness, histological grade and recurrence. This was not seen for urothelial carcinoma from patients from non‐contaminated areas. A close correlation was also found between DAPK promoter methylation and low‐intensity DAPK expression, as detected by immunohistochemistry ( P = 0.037). Conclusion: Exposure to arsenic may induce DAPK promoter hypermethylation and inactivate the function of DAPK in urothelial carcinoma. This could prove to be a key molecular event contributing to the malignant phenotype of tumour arising in patients from arsenic‐contaminated environments.