Original Article Messenger RNA expression and methylation of selected tumor-suppressor genes and risk of ovarian cancer – a case-control analysis
Jiaze An, Qingyi Wei, Zhensheng Liu, Karen H. Lu, Xi Cheng, Gordon B Mills, Li-E Wang
Departments of Epidemiology, Gynecologic Oncology, and Systems Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA
Received May 31, 2009; accepted June 23, 2009; available online June 30, 2009
Abstract: 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 transcriptase polymerase chain reaction) and methylation status (by methylation-specific polymerase chain reaction) of five selected genes (BRCA1, BRCA2, hMLH1, MGMT, and DNMT3B) in tumors from the cases and normal ovaries from the controls. We found that mean mRNA expression levels of the five genes were lower in tumors than in normal ovaries, with differences statistically significant for BRCA2 and hMLH1 but borderline for MGMT. 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 tumor-suppressor genes BRCA2, hMLH1, and MGMT, likely due to molecular mechanisms in addition to the promoter methylation, may be a biomarker for ovarian cancer risk in this study population. Larger studies are needed to validate our findings. (IJMEG905001).
Key words: Case-control study, DNA repair, epigenetics, molecular epidemiology, ovarian cancer
Address all correspondence to: Li-E Wang, MD Department of Epidemiology, Unit 1365 The University of Texas M. D. Anderson Cancer Center 1515 Holcombe Blvd. Houston, TX 77030 Tel: 713-792-3020; Fax: 713-563-0999 E-mail: firstname.lastname@example.org.