Estrogen and Progesterone Receptors in Colorectal Cancer and Surrounding Mucosa

Raigoso, P; Sanz, Lourdes; Vizoso, F; Llana, B. Fernández; Quintela,; Roibás, Antonio; P, Vérez; García-Muñiz, I L

doi:10.1177/172460080101600407

Cited by 11 publications

(4 citation statements)

References 18 publications

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“…Recent re-analysis of world wide data on the relationship between hormone replacement therapy and breast cancer showed that the risk of this cancer may be increased in women who are taking estrogen [123] . Estrogen receptors are reported to be present in colorectal tissue and colorectal adenocarcinoma and ER-β is found to be the predominate receptor expressed in colonic tissue [124][125][126][127][128][129][130] (Table 1).…”

Section: Surrogate End Point In Colon Cancermentioning

confidence: 99%

Molecular markers and targets for colorectal cancer prevention

Janakiram

Rao

2008

Acta Pharmacol Sin

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Colorectal cancer is the third most prevalent cancer in the world. If detected at an early stage, treatment often might lead to cure. As prevention is better than cure, epidemiological studies reveal that having a healthy diet often protects from promoting/ developing cancer. An important consideration in evaluating new drugs and devices is determining whether a product can effectively treat a targeted disease. There are quite a number of biomarkers making their way into clinical trials and few are awaiting the preclinical efficacy and safety results to enter into clinical trials. Researchers are facing challenges in modifying trial design and defining the right control population, validating biomarker assays from the biological and analytical perspective and using biomarker data as a guideline for decision making. In spite of following all guidelines, the results are disappointing from many of the large clinical trials. To avoid these disappointments, selection of biomarkers and its target drug needs to be evaluated in appropriate animal models for its toxicities and efficacies. The focus of this review is on the few of the potential molecular targets and their biomarkers in colorectal cancers. Strengths and limitations of biomarkers/surrogate endpoints are also discussed. Various pathways involved in tumor cells and the specific agents to target the altered molecular biomarker in biomolecular pathway are elucidated. Importance of emerging new platforms siRNAs and miRNAs technology for colorectal cancer therapeutics is reviewed.

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Section: Surrogate End Point In Colon Cancermentioning

confidence: 99%

Molecular markers and targets for colorectal cancer prevention

Janakiram

Rao

2008

Acta Pharmacol Sin

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“…16 Progesterone and oestradiol receptors have been found in normal colonic tissue. 17 Multiple studies failed to show a clear or consistent effect of female sex hormones on gastric emptying, small bowel transit and colonic transit with either longer orocecal transit time in the luteal phases compared with the follicular phases 9,11,12 or no significant variation with the phase of the menstrual cycle in whole gut, 18,19 orocecal, 19 or colonic transit. 8 Our aim was to clarify the effects on colonic transit of doses of progesterone and oestradiol that intended to mimic the levels occurring in the luteal phase of the menstrual cycle and the withdrawal of sex hormones, as occurs immediately prior to menstruation.…”

Section: Introductionmentioning

confidence: 99%

“…At the tissue level, sex hormones inhibit muscle contractility in a variety of sites, including uterus, gall bladder, 14 lower oesophageal sphincter, 15 and colon 16 . Progesterone and oestradiol receptors have been found in normal colonic tissue 17 …”

Section: Introductionmentioning

confidence: 99%

Effect of female sex hormone supplementation and withdrawal on gastrointestinal and colonic transit in postmenopausal women

Gonenne

Esfandyari

Camilleri

et al. 2006

Neurogastroenterology Motil

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Females are disproportionately affected by constipation, which is often aggravated during pregnancy. Bowel function also changes during the luteal phase of the menstrual cycle. The aim was to compare the effects of acute administration of female sex steroids on gastric emptying, small bowel transit and colonic transit in healthy postmenopausal subjects. A second aim was to determine whether withdrawal of the hormones was associated with a change in transit. Forty-nine postmenopausal females were randomized to receive for 7 days 400 mg day(-1) micronized progesterone, 0.2 mg day(-1) oestradiol, combination of the two, or placebo. Treatment groups were balanced on age. Participants underwent whole gut transit measurement by scintigraphy using a 99m-labeled technetium-egg meal and 111-labeled indium-charcoal via a delayed-release capsule. Transit measurement was repeated after withdrawal of the study medications. The primary endpoints were ascending colon (AC) emptying half-life time (t1/2) and colonic geometric centre (GC) at 24 h. Secondary analysis variables were GC at 4 and 48 h, gastric emptying t1/2 and colonic filling at 6 h. There was a significant overall effect of progesterone on colonic transit with shorter AC emptying t1/2 and significantly greater colonic GC at 48 h. No transit endpoints were altered by oestradiol or combined hormonal treatment relative to placebo. Oestradiol and progesterone resulted in looser stool consistency. Withdrawal of the hormone supplement was not associated with significant alteration in transit. Micronized progesterone does not retard colonic transit in postmenopausal females.

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“…Because of the similarities in BMI associations for women exposed to estrogen and for men, it has been hypothesized that androgen, as well as estrogen, might be related to colon cancer risk. Both estrogen and androgen receptors are present in colorectal tissue (7)(8)(9)(10)(11)(12). Most of the actions of estrogens and androgens seem to be exerted through the respective receptors (13,14), suggesting that the estrogen receptor and androgen receptor may be important in regulating colorectal cancer risk associated with these hormones.…”

Section: Introductionmentioning

confidence: 99%

Associations between ERα, ERβ, and AR Genotypes and Colon and Rectal Cancer

Slattery¹,

Sweeney²,

Murtaugh³

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Estrogen and androgens are thought to be involved in the etiology of colorectal cancer. We evaluate genetic variants of the estrogen receptor genes (ERa and ERb) and the androgen receptor gene (AR). We use data from two large case-control studies of colon (n = 1,580 cases and 1,968 controls) and rectal (n = 797 cases and 1,016 controls) cancer. We evaluated the 351A>G XbaI polymorphism of ERa, the 1,082 G>A and CA repeat polymorphisms of ERb, and the CAG repeat of AR. Having two 25 or more CA repeats in ERb was associated with an increased relative risk of colon cancer in women [odds ratio (OR), 2.13; 95% confidence interval (95% CI), 1.24-3.64] but not in men (P interaction relative excess risk from interaction < 0.01; multiplicative = 0.03). Increasing number of AR CAG repeats was directly associated with colon cancer among men (OR, 1.28; 95% CI, 1.06-1.54), but not women (OR, 0.83; 95% CI, 0.68-1.02); the interaction P value for AR gene Â sex was <0.01. Taking hormone replacement therapy (HRT) was associated with a reduced risk of colon cancer in the presence of the R allele of the ERb gene, whereas an R allele was associated with increased risk among postmenopausal women who did not take HRT. Postmenopausal women not using HRT who had z25 CA repeats of the ERb gene had over a 6-fold increased risk of colon cancer (OR, 6.71; 95% CI, 2.89-15.6). Our results suggest that the ERb gene is more important than ERA in the etiology of colorectal cancer. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2936 -42)

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Estrogen and Progesterone Receptors in Colorectal Cancer and Surrounding Mucosa

Cited by 11 publications

References 18 publications

Molecular markers and targets for colorectal cancer prevention

Molecular markers and targets for colorectal cancer prevention

Effect of female sex hormone supplementation and withdrawal on gastrointestinal and colonic transit in postmenopausal women

Associations between ERα, ERβ, and AR Genotypes and Colon and Rectal Cancer

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