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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Prognostic significance of gene-specific promoter hypermethylation in breast cancer patients.

Authors: Cho, Yoon Hee; Shen, Jing; Gammon, Marilie D; Zhang, Yu-Jing; Wang, Qiao; Gonzalez, Karina; Xu, Xinran; Bradshaw, Patrick T; Teitelbaum, Susan L; Garbowski, Gail; Hibshoosh, Hanina; Neugut, Alfred I; Chen, Jia; Santella, Regina M

Published In Breast Cancer Res Treat, (2012 Jan)

Abstract: The association between promoter methylation status and survival was investigated in a large cohort of women with breast cancer, participants in the Long Island Breast Cancer Study Project. Archived tumor tissues (n = 839) were collected from women diagnosed with a first primary invasive or in situ breast cancer in 1996-1997. Vital status was followed through the end of 2005 with a mean follow-up time of 8 years. Promoter methylation of eight breast cancer-related genes was assessed by MethyLight. The frequencies of methylation for HIN1, RASSF1A, DAPK1, GSTP1, CyclinD2, TWIST, CDH1 and RARβ were 62.9, 85.2, 14.1, 27.8, 19.6, 15.3, 5.8 and 27.6%, respectively. Since survival rates of in situ and invasive breast cancers are substantially different, survival analyses were conducted within 670 invasive cases with complete data on all genes. Age-adjusted Cox proportional hazards models revealed that GSTP1, TWIST and RARβ methylation was significantly associated with higher breast cancer-specific mortality. Methylation of GSTP1 and RARβ was significantly associated with higher all-cause mortality. To investigate the relationship between the number of methylated genes and breast cancer-specific mortality, we included previously published MethyLight data on p16 and APC methylation status. Breast cancer-specific mortality increased in a dose-dependent manner with increasing number of methylated genes (P (trend) = 0.002), although confidence intervals were wide. Our results suggest that promoter methylation, particularly for a panel of genes, has the potential to be used as a biomarker for predicting prognosis in breast cancer.

PubMed ID: 21837480 Exiting the NIEHS site

MeSH Terms: Breast Neoplasms/genetics*; Breast Neoplasms/mortality*; Breast Neoplasms/pathology; Cohort Studies; DNA Methylation/genetics*; Female; Follow-Up Studies; Glutathione S-Transferase pi/genetics; Humans; Nuclear Proteins/genetics; Prognosis; Promoter Regions, Genetic*; Receptors, Retinoic Acid/genetics; Surveys and Questionnaires; Twist-Related Protein 1/genetics

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