Epigenetics and Genetics in Endometrial Cancer: New Carcinogenic Mechanisms and Relationship with Clinical Practice

Abstract

Endometrial cancer is the seventh most common cancer worldwide among females. An increased incidence and a younger age of patients are also predicted to occur, and therefore elucidation of the pathological mechanisms is important. However, several aspects of the mechanism of carcinogenesis in the endometrium remain unclear. Associations with genetic mutations of cancer-related genes have been shown, but these do not provide a complete explanation. Therefore, epigenetic mechanisms have been examined. Silencing of genes by DNA hypermethylation, hereditary epimutation of DNA mismatch repair genes and regulation of gene expression by miRNAs may underlie carcinogenesis in endometrial cancer. New therapies include targeting epigenetic changes using histone deacetylase inhibitors. Some cases of endometrial cancer may also be hereditary. Thus, patients with Lynch syndrome which is a hereditary disease, have a higher risk for developing endometrial cancer than the general population. Identification of such disease-related genes may contribute to early detection and prevention of endometrial cancer.

KEYWORDS::

• DNA hypermethylation
• DNA mismatch repair
• endometrial cancer
• epimutation
• HDAC inhibitor
• hMLH1
• lower uterine segment
• Lynch syndrome
• miRNA
• MMR

Financial & competing interests disclosure

The authors gratefully acknowledge grant support from the Japan Society for the Promotion of Science (JSPS) through a Grant-in-Aid for Scientific Research (KAKENHI); a Grant-in-Aid for Scientific Research (C) (22591866) and a Grant-in-Aid for Young Scientists (B) (21791573); the Ichiro Kanehara Foundation; and the Keio University Medical Science Fund through a Research Grant for Life Sciences and Medicine. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The authors gratefully acknowledge grant support from the Japan Society for the Promotion of Science (JSPS) through a Grant-in-Aid for Scientific Research (KAKENHI); a Grant-in-Aid for Scientific Research (C) (22591866) and a Grant-in-Aid for Young Scientists (B) (21791573); the Ichiro Kanehara Foundation; and the Keio University Medical Science Fund through a Research Grant for Life Sciences and Medicine. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.