Open AccessMethylation of estrogen receptor 1 in colorectal adenomas is not age‐dependent, but is correlated with K‐ras mutation
Author(s) -
Horii Joichiro,
Hiraoka Sakiko,
Kato Jun,
Saito Shunsuke,
Harada Keita,
Fujita Hideyuki,
Kaji Eisuke,
Yamamoto Kazuhide
Publication year - 2009
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01140.x
Subject(s) - methylation , dna methylation , estrogen receptor alpha , estrogen receptor , adenoma , medicine , methyltransferase , malignancy , colorectal cancer , estrogen , biology , endocrinology , cancer research , cancer , breast cancer , genetics , gene , gene expression
The promoter region of estrogen receptor 1 ( ESR1 ) has been shown to be methylated in normal colorectal mucosa in an age‐dependent manner. However, the methylation of this region in colorectal tumors has not sufficiently been investigated. The methylation status of ESR1 in 105 colorectal adenoma tissues was examined by MethyLight and presented as the percentage of methylated references (PMR). Factors that affect the PMR of ESR1 in adenomas were determined using parameters including patient age, sex, past history of malignancy, family history of colorectal cancer, smoking and drinking habits, clinical characteristics of adenomas (location, size, macroscopic appearance, and histology), and K‐ras mutation. Multiple linear regression revealed that the PMR was not correlated with patient age. K‐ras mutation was significantly correlated with the higher methylation status of ESR1 in adenoma ( t ‐value = 3.21, P = 0.0018), whereas alcohol exposure was significantly correlated with lower methylation status ( t ‐value = –2.37, P = 0.02). Because methylation of O 6 ‐methylguanine DNA methyltransferase ( MGMT ) has been reported to be correlated with K‐ras G‐to‐A transition, methylation of ESR1 was compared with that of MGMT with regard to K‐ras mutation. Contrary to expectations, methylation of MGMT was not significantly correlated with K‐ras G‐to‐A transition, but that of ESR1 was strongly correlated with K‐ras G‐to‐A transition. Thus, the methylation status of ESR1 in adenomas was not correlated with patient age, but was associated with K‐ras mutation, suggesting that methylation of ESR1 in tumors functions differently from that in normal colon mucosa. ( Cancer Sci 2009; 100: 1005–1011)