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Messenger rna expression and methylation of candidate tumor-suppressor genes and risk of ovarian cancer-a case-control analysis

Publication ,  Journal Article
An, J; Wei, Q; Liu, Z; Lu, KH; Cheng, X; Mills, GB; Wang, LE
Published in: International Journal of Molecular Epidemiology and Genetics
July 21, 2010

To investigate the association of expression and promoter methylation of tumor-suppressor genes with risk of ovarian cancer, we conducted a case-control study of 102 patients with serous epithelial ovarian cancer and 100 patients without ovarian cancers. We measured mRNA expression levels (by real-time reverse transcription polymerase chain reaction) and methylation status (by methylation-specific polymerase chain reaction) of five candidate genes (BRCA1, BRCA2, hMLH1, MGMT, and DNMT3B) in tumors from the cases and normal ovaries from the controls. We found that mRNA expression levels of the five genes were decreased in tumors than in normal ovaries with 0.39-fold for BRCA1, 0.25-fold for BRCA2, 0.42-fold for hMLH1, 0.45-fold for MGMT, and 0.87-fold for DNMT3B, calculated by the 2-δδCT method. Ovarian cancer risk (odds ratios, ORs) was associated with low expression of all genes (2.95 [95% confidence interval (CI), 1.51 - 5.78] for BRCA1, 3.65 (95% CI, 1.82 - 7.30) for BRCA2, 5.25 (95% CI, 2.52 - 10.96) for hMLH1, and 4.72 (95% CI, 2.32 - 9.62) for MGMT) but not DNMT3B. However, methylation status was not associated with gene expression levels in the tumors, except for hMLH1 whose mean (± SD) gene expression was significantly lower in methylated (13.0 ± 7.6) than in unmethylated (31.2 ± 44.8) tumors (P < 0.001). We concluded that low mRNA expression of these tumorsuppressor genes, likely due to molecular mechanisms in addition to the promoter methylation in some instances, may be a biomarker for ovarian cancer risk in this study population. Larger studies are needed to validate our findings.

Duke Scholars

Published In

International Journal of Molecular Epidemiology and Genetics

EISSN

1948-1756

Publication Date

July 21, 2010

Volume

1

Issue

1

Start / End Page

1 / 10

Related Subject Headings

  • 1117 Public Health and Health Services
  • 0604 Genetics
 

Citation

APA
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ICMJE
MLA
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An, J., Wei, Q., Liu, Z., Lu, K. H., Cheng, X., Mills, G. B., & Wang, L. E. (2010). Messenger rna expression and methylation of candidate tumor-suppressor genes and risk of ovarian cancer-a case-control analysis. International Journal of Molecular Epidemiology and Genetics, 1(1), 1–10.
An, J., Q. Wei, Z. Liu, K. H. Lu, X. Cheng, G. B. Mills, and L. E. Wang. “Messenger rna expression and methylation of candidate tumor-suppressor genes and risk of ovarian cancer-a case-control analysis.” International Journal of Molecular Epidemiology and Genetics 1, no. 1 (July 21, 2010): 1–10.
An J, Wei Q, Liu Z, Lu KH, Cheng X, Mills GB, et al. Messenger rna expression and methylation of candidate tumor-suppressor genes and risk of ovarian cancer-a case-control analysis. International Journal of Molecular Epidemiology and Genetics. 2010 Jul 21;1(1):1–10.
An, J., et al. “Messenger rna expression and methylation of candidate tumor-suppressor genes and risk of ovarian cancer-a case-control analysis.” International Journal of Molecular Epidemiology and Genetics, vol. 1, no. 1, July 2010, pp. 1–10.
An J, Wei Q, Liu Z, Lu KH, Cheng X, Mills GB, Wang LE. Messenger rna expression and methylation of candidate tumor-suppressor genes and risk of ovarian cancer-a case-control analysis. International Journal of Molecular Epidemiology and Genetics. 2010 Jul 21;1(1):1–10.

Published In

International Journal of Molecular Epidemiology and Genetics

EISSN

1948-1756

Publication Date

July 21, 2010

Volume

1

Issue

1

Start / End Page

1 / 10

Related Subject Headings

  • 1117 Public Health and Health Services
  • 0604 Genetics