Sex-specific differences in the expression levels of estrogen receptor subtypes in colorectal cancer

Gend Med. 2008 Sep;5(3):209-17. doi: 10.1016/j.genm.2008.07.005.


Background: Altered expression of estrogen receptors alpha and beta (ERalpha and ERbeta) has been hypothesized to play a role in carcinogenesis. However, little is known about the sex-specific differences of ER expression in colorectal cancer (CRC).

Objective: This study examined ERalpha and ERbeta protein levels in male and female patients with CRC.

Methods: Using Western blot analysis, the intensity of ERalpha and ERbeta protein levels was determined in tumor tissue and in corresponding normal colon mucosa from patients with CRC.

Results: All 64 white patients (33 men, mean [SEM] age 64.1 [13.1] years, age range 26-90 years; 31 women, mean age 68.5 [14.5] years, age range 39-91 years [4 were premenopausal at time of surgery]) expressed ERalpha and ERbeta protein in normal colon mucosa, and there were no significant differences between men and women. In tumor tissue, a significantly increased ERalpha protein level was observed in men (P = 0.02 vs normal tissue), whereas in women, the ERalpha level did not differ significantly between tumor and normal tissue. The level of ERbeta protein in CRC was significantly reduced in both men and women, but more so in men (P = 0.04 vs women). Furthermore, in men, the ERbeta level was significantly lower in poorly differentiated tumors than in moderately differentiated tumors (P < 0.03), whereas in women, poor differentiation of the tumor was not associated with a significant decrease of ERbeta level.

Conclusions: Altered levels of ER subtypes resulting in an increased ERalpha:ERbeta ratio were found in patients with CRC. The observation of significantly greater alterations in men than in women supports the hypothesis of sex-specific differences in the pathogenesis of CRC.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Colorectal Neoplasms / metabolism*
  • Estrogen Receptor alpha / metabolism*
  • Estrogen Receptor beta / metabolism*
  • Female
  • Humans
  • Intestinal Mucosa / metabolism*
  • Male
  • Middle Aged
  • Sex Characteristics


  • Estrogen Receptor alpha
  • Estrogen Receptor beta