Researchers at the University at Buffalo have identified particular genes that are most prone to become cancer promoters when exposed to a process called DNA promoter hypermethylation.
Hypermethylation is a process that causes genes, which support normal cell development, to generate proteins that result in malignant behavior, or unregulated cell growth.
AdvertisementSo far, data has been very inadequate regarding the mechanism and causes of hypermethylation, particularly for hypermethylation in breast cancer.
The idea behind the current study was to find out how DNA hypermethylation relates to other characteristics of breast tumors.
"It is well known that mutation in genes -- alterations in their sequence -- is one of the characteristics of tumors responsible for some of their disease properties. In addition, it is now becoming clear that other changes in the DNA may also contribute to the development of cancer," said Menghua Tao, Ph.D., research assistant professor of social and preventive medicine in the UB School of Public Health and Health Professions and first author on the study.
Cancer epidemiologists examined methylation significance in three genes, known as E-cadherin, p16 and retinoic acid B2 receptor (RAR-B2), using tissue samples from 887 breast cancers. The samples were taken from women 35-79 years old who participated in the Western New York Exposures and Breast Cancer Study (WEB study).
Extensive personal interviews were used to gather information on possible breast-cancer risk factors and perplexing factors.
"We found that hypermethylation of E-cadherin, but not of the other genes, was more likely to occur in estrogen receptor (ER)-negative than in ER-positive tumors," said Tao.
ER-positive tumors are hose that express receptors for the hormone estrogen. Such tumors counter treatments that block these receptors.
"Similarly, hypermethylation of E-cadherin was more frequent among progestin receptor (PR)-negative cases. Compared to tumors that were both ER- and PR-positive, tumors that were both ER- and PR-negative were more likely to be E-cadherin hypermethylated. However, hypermethylation of E-cadherin, p16 and RAR-?2 was not associated with other clinicopathological features of breast cancer, such as tumor size, histological grade or nuclear grade," said Tao.
"Our data suggested that promoter hypermethylation is common in breast cancer," Tao added. "Because promoter hypermethylation is potentially reversible, identifying cancers with different hypermethylation may have important consequences for breast-cancer treatment."
Jo Freudenheim, Ph.D., professor and chair of the UB Department of Social and Preventive Medicine, heads the WEB Study.