Estrogen receptor β (ERβ) is the predominant ER in the colorectal epithelium, whose expression is greatly reduced in colorectal cancer compared with normal colon tissue.
ESR2rs1256049 CT/TT genotypes were associated with reduced risk of CRC (odds ratio [OR], 0.7, 95% confidence interval [CI], 0.5-1.0), while rs4986938 CT/TT genotypes were associated with increased risk of CRC (OR, 1.5, 95% CI, 1.0-2.1).
We explored the effect modification of MHT-associated CRC risk in postmenopausal women by 47 polymorphisms with known or putative functional relevance in 16 candidate genes related to hormone metabolism (COMT, CYP1A1, CYP1A2, CYP1B1, CYP2C9, CYP2C19, CYP3A4, CYP17A1, GSTP, and HSD17B1), transport (ABCB1), and signaling (ESR1, ESR2, SHBG, PGR, and NR1I2).
These findings implicate a role of ESR2 in the risk for developing CRC in women and suggest that HSD17B1, ABCB1, and SHBG genes may contribute to sex steroid-mediated effects on CRC development.
The incidence of colorectal cancer was significantly different according to the ESR2 CA repeat genotype only among females (SS, 37/202 = 18.3%; SL, 19/332 = 5.7%; LL, 5/155 = 3.2%, P < 0.0001).
Recent advances in the molecular biology of CRC, specifically in microsatellite status, estrogen hormone and estrogen receptor beta, have led to greater understanding of the effect of estrogen in colorectal carcinogenesis.
The implications of this pathway include new possibilities to treat or prevent colorectal cancer with targeted endocrine drugs and the potential of ERbeta as a novel diagnostic tool.
In this study we assessed the ERβ expression in the intestinal mucosa of FAP patients to verify its possible involvement in tumor progression in colorectal cancer.