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Carcinogenic mechanisms of endometrial cancer: Involvement of genetics and epigenetics
Author(s) -
Banno Kouji,
Yanokura Megumi,
Iida Miho,
Masuda Kenta,
Aoki Daisuke
Publication year - 2014
Publication title -
journal of obstetrics and gynaecology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 50
eISSN - 1447-0756
pISSN - 1341-8076
DOI - 10.1111/jog.12442
Subject(s) - endometrial cancer , pten , epigenetics , carcinogenesis , cancer research , dna methylation , cdh1 , cancer , medicine , tumor suppressor gene , microrna , biology , genetics , oncology , gene , pi3k/akt/mtor pathway , gene expression , apoptosis , cadherin , cell
Endometrial cancer is increasing worldwide and the number of patients with this disease is likely to continue to grow, including younger patients. Many endometrial cancers show estrogen‐dependent proliferation, but the carcinogenic mechanisms are unknown or not completely explained beyond mutations of single oncogenes and tumor suppressor genes. Possible carcinogenic mechanisms include imbalance between endometrial proliferation by unopposed estrogen and the mismatch repair ( MMR ) system; hypermethylation of the MMR gene h MLH 1 ; mutation of PTEN , β‐catenin and K ‐ras genes in type I endometrial cancer and of HER ‐2/neu and p53 genes in type II endometrial cancer; hypermethylation of SPRY 2 , RASSF1A , RSK 4 , CHFR and CDH 1 ; and methylation of tumor suppressor microRNAs, including mi R ‐124 , mi R ‐126 , mi R ‐137 , mi R ‐491 , mi R ‐129‐2 and mi R ‐152 . Thus, it is likely that the carcinogenic mechanisms of endometrial cancer involve both genetic and epigenetic changes. Mutations and methylation of MMR genes induce various oncogenic changes that cause carcinogenesis, and both MMR mutation in germ cells and methylation patterns may be inherited over generations and cause familial tumorigenesis. Determination of the detailed carcinogenic mechanisms will be useful for prevention and diagnosis of endometrial cancer, risk assessment, and development of new treatment strategies targeting MMR genes.