Aberrant DNA methylation of some tumor suppressor genes in lung cancers from workers with chromate exposure

Our previous studies revealed a variety of genetic changes in lung cancers from chromate‐exposed workers (chromate lung cancer). In the present study, we examined epigenetic changes in chromate lung cancers. Nested‐methylation‐specific PCR was employed in studying the methylation of CpG islands in t...

Full description

Saved in:
Bibliographic Details
Published inMolecular carcinogenesis Vol. 50; no. 2; pp. 89 - 99
Main Authors Ali, Abdellah H. K., Kondo, Kazuya, Namura, Toshiaki, Senba, Yoshitaka, Takizawa, Hiromitsu, Nakagawa, Yasushi, Toba, Hiroaki, Kenzaki, Koichiro, Sakiyama, Shoji, Tangoku, Akira
Format Journal Article
LanguageEnglish
Published Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.02.2011
Wiley Subscription Services, Inc
Subjects
Online AccessGet full text

Cover

Loading…
More Information
Summary:Our previous studies revealed a variety of genetic changes in lung cancers from chromate‐exposed workers (chromate lung cancer). In the present study, we examined epigenetic changes in chromate lung cancers. Nested‐methylation‐specific PCR was employed in studying the methylation of CpG islands in the APC, MGMT, hMLH1 genes in 36 chromate lung cancers and 25 nonchromate lung cancers. Methylation in chromate lung cancers was detected at 86% for APC, 20% for MGMT, and 28% for hMLH1. Whereas, it occurred at lower frequencies in nonchromate lung cancers, particularly in APC (44%) and hMLH1 (0%) genes. Our previous study showed that methylation of p16 gene in chromate lung cancer and nonchromate lung cancer was 33% and 26%, respectively. The mean methylation index (MI), a reflection of the overall methylation status, was significantly higher in chromate lung cancers than nonchromate lung cancers (0.41 vs. 0.21, P = 0.001). Methylation of multiple genes (particularly hMLH1, p16, and APC genes) had experienced more than 15 yr of chromate exposure in chromate lung cancer (MI: <15 yr; 0.19, ≥15 yr, 0.42). There is a significant correlation of p16 and hMLH1 methylation with the expressional decrease or loss of the corresponding gene products (P = 0.037 and 0.024) respectively, and an inverse correlation between APC and MGMT methylation (P = 0.014). This study provides a novel evidence for the chromium carcinogenesis that chromate lung cancer is linked to the progressive methylation of some tumor suppressor genes, which may be related to genomic instability. © 2010 Wiley‐Liss, Inc.
Bibliography:ark:/67375/WNG-952RC9SZ-8
ArticleID:MC20697
istex:93BBC9C8E1A4C2E0B73C75D244DBA77F205F6B4B
ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
ISSN:0899-1987
1098-2744
1098-2744
DOI:10.1002/mc.20697