Messenger RNA expression and methyiation of candidate tumor-suppressor genes and risk of ovarian cancer–a case-control analysis

International Journal of Molecular Epidemiology and Genetics

Jiaze An¹  Li-E Wang¹  Zhensheng Liu¹  Karen H Lu¹  Xi Cheng¹  Gordon B Mills¹  Qingyi Wei¹ 

关键词: Case-control study;    DNA repair;    epigenetics;    molecular epidemiology;    ovarian cancer;   

DOI  :  

学科分类：流行病学

来源: e-Century Publishing Corporation

【 摘 要 】

To investigate the association of expression and promoter methyiation 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 methyiation status (by methylation-specific polymerase chain reaction) of five candidate genes (BRCA1, BRCA2, hMLHl, 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 hMLHl, 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 hMLHl, and 4.72 (95% CI, 2.32 - 9.62) for MGMT) but not DNMT3B. However, methyiation status was not associated with gene expression levels in the tumors, except for hMLHl 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 tumor-suppressor genes, likely due to molecular mechanisms in addition to the promoter methyiation in some instances, may be a biomarker for ovarian cancer risk in this study population. Larger studies are needed to validate our findings.

【 授权许可】

Unknown