Estrogens and Colorectal Cancer

Abstract

In recent years, several lines of epidemiologic, clinical and experimental evidences have been reported showing that estrogen hormones may be involved in malignant colorectal tumors. The sex differences in site-specific incidence, the increased incidence of colonic cancer in women with breast cancer, the protective effect of increasing parity and the reduced risk among women taking postmenopausal hormones, are all elements suggesting that sex hormones may play a role. Male rats experimentally exposed to the carcinogen dimethylhydrazine, have twice the risk of developing colon cancer and significantly shorter survival times than their female counterparts. Along with the clinical, experimental and epidemiologic findings there are also biologic reasons why estrogen may be protective. Most estrogen action appears to be exerted via the estrogen receptors (ERs) on target cells. ERs have been reported in several solid tumors including gastrointestinal neoplasms such as esophageal, gallbladder, gastric and colorectal cancer. At the end of 1995, a second ER (ER-beta) was cloned from the rat prostate cDNA library and subsequently, the human and mouse homologs. Its demonstration in normal and neoplastic human colorectal tissues and "in vitro" in colonic epithelial cells, has renewed interest in investigating the existence of two ER subtypes. The presence of two ERs could explain the selective actions of estrogens on different target tissues and, particularly, on the gastrointestinal tract. Finally, our studies suggest that estrogens and their receptors play an important role in the growth and progression of colorectal tumors, by interacting with other molecules required for cell proliferation like growth factors and polyamines.

Oral Contraceptive Use, Reproductive Factors, and Colorectal Cancer Risk: Findings from Wisconsin

“…Bile acid secretion is potentially damaging to the colonic mucosa and may prompt the initiation or promotion of malignant growth (18,39,51). Supplementing exogenous estrogen decreases bile acid levels (51,52). The absorption of bile acids in the proximal bowel provides support for a protective effect for colon but not rectal cancer (39,51).…”

Expression of estrogen receptor ® in human colorectal cancer

“…Several epidemiologic studies have shown that colon cancer might be influenced by steroid hormones [1][2][3] , and estrogen use might be associated with a low risk of colon cancer [21][22][23][24][25][26][27] . Some experimental results indicated that estrogen had a trophic effect on colon cancer [1,[11][12] .…”

“…Animal models showed that male rats had a higher risk developing colon cancer compared with their female counterparts when exposed to dimethylhydrazine, an experimental carcinogen. The results indicated that 17β-oestradiol (E 2 ) treatment could significantly reduce the frequency of dimethylhydrazine-induced large intestinal tumors in rats [1][2][3] . These evidences suggest that estrogen maybe involved in the growth of colonic tumors.…”

Nitric oxide impairs the 17β-estradiol-induced apoptosis in human colon adenocarcinoma cells

“…DLD-1 cells contain constitutively only the ERb-1 isoform and lack any ERa isoform (Fiorelli et al 1999, Di Leo et al 2001, Acconcia et al 2005a. Cells were routinely grown in air containing 5% CO 2 in modified, phenol red-free, RPMI-1640 medium, containing 10% (v/v) charcoal-stripped fetal calf serum, L-glutamine (2.0 mM), gentamicin (0.1 mg/ml), and penicillin (100 U/ml).…”