Journal Article

Aberrant promoter hypermethylation in serum DNA from patients with silicosis

Shigeki Umemura, Nobukazu Fujimoto, Akio Hiraki, Kenichi Gemba, Nagio Takigawa, Keiichi Fujiwara, Masanori Fujii, Hiroshi Umemura, Mamoru Satoh, Masahiro Tabata, Hiroshi Ueoka, Katsuyuki Kiura, Takumi Kishimoto and Mitsune Tanimoto

in Carcinogenesis

Volume 29, issue 9, pages 1845-1849
Published in print September 2008 | ISSN: 0143-3334
Published online July 2008 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgn169
Aberrant promoter hypermethylation in serum DNA from patients with silicosis

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It is well established that patients with silicosis are at high risk for lung cancer; however, it is difficult to detect lung cancer by chest radiography during follow-up treatment of patients with silicosis because of preexisting diffuse pulmonary shadows. The purpose of this study is to evaluate the usefulness of detection of serum DNA methylation for early detection of lung cancer in silicosis. Serum samples from healthy controls (n = 20) and silicosis patients with (n = 11) and without (n = 67) lung cancer were tested for aberrant hypermethylation at the promoters of the DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT), p16INK4a, ras association domain family 1A (RASSF1A), the apoptosis-related gene death-associated protein kinase (DAPK) and retinoic acid receptor β (RARβ) by methylation-specific polymerase chain reaction. Aberrant promoter methylation in at least one of five tumor suppressor genes was detected more frequently in the serum DNA of silicosis patients with lung cancer than in that of patients without it (P = 0.006). Furthermore, the odds ratio of having lung cancer was 9.77 (P = 0.009) for those silicosis patients with methylation of at least one gene. Extended exposure to silica (>30 years) was correlated with an increased methylation frequency (P = 0.017); however, methylation status did not correlate with age, smoking history or radiographic findings of silicosis. These results suggest that testing for aberrant promoter methylation of tumor suppressor genes using serum DNA may facilitate early detection of lung cancer in patients with silicosis.

Journal Article.  4216 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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