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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Postmenopausal estrogen deficiency may result in a wide variety of physiologic disorders, including vasomotor symptoms, urogenital atrophy, an increase in the risk of coronary heart disease, osteoporotic fractures, and Alzheimer's disease. The growing body of evidence, including much that is newly published, demonstrating that hormone replacement therapy (HRT) can largely prevent or mitigate these sequelae, will be reviewed in this paper. The efficacy of HRT in alleviating vasomotor and urogenital discomfort, the most common symptoms of postmenopausal estrogen deficiency, is well established. Evidence from over 30 epidemiologic studies indicates that estrogen reduces the risk of coronary heart disease (CHD) by 50%. The risk of major CHD has been found to be markedly reduced in women who receive combined estrogen/progestogen therapy compared to nonusers (or estrogen-alone users). Estrogen is recommended as the modality of choice to prevent bone loss: data supporting a positive effect of estrogen on the risk of wrist and vertebral fracture are quite favorable. Similarly, outcomes of recent investigations have demonstrated a positive impact of HRT on both psychological function and the risk of osteoarthritis. In addition, HRT substantially reduces the risk of colon cancer. Moreover, the potential for HRT to delay the progression or reduce the risk for developing Alzheimer's disease is a new area of research that shows promise. Improvements in quality-of-life assessments have also been reported in conjunction with the relief of menopausal symptoms by HRT. Clinicians should be aware of the large amount of new evidence that strengthens the case for wider use of HRT. Based on these new data, physicians may conclude that HRT would benefit the majority of their postmenopausal patients and thus encourage HRT use in the absence of known risk factors.
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PMID:Benefits of hormone replacement therapy--overview and update. 939 82

We investigated the association between hormone replacement therapy (HRT), primarily conjugated estrogens with or without medroxyprogesterone acetate, and colon cancer risk in a nested case-control study among women ages 55-79 years enrolled in Group Health Cooperative, a health maintenance organization in Washington state. Cases were diagnosed between 1984 and 1993. We selected controls randomly from enrollment files. HRT use was ascertained from a computerized database containing virtually all prescriptions dispensed since 1977. Among subjects with at least 5 years of pharmacy database information before reference date (1 year before diagnosis date), there were 341 cases of incident colon cancer and 1,679 controls. Estrogen use during the 5 years before reference date was not associated with risk of colon cancer [odds ratio (OR) = 0.85 and 95% confidence interval (CI) = 0.57-1.27 for 1-749 estrogen tablets; OR = 0.97 and 95% CI = 0.68-1.40 for > or =750 estrogen tablets]. An analysis including only women with at least 10 years of pharmacy database coverage found no association with use during the 10 years before reference date [OR = 1.07 (95% CI = 0.61-1.86) for 1-749 estrogen tablets; OR = 1.11 (95% CI = 0.69-1.80) for 750 or more estrogen tablets]. These results do not support the hypothesis that recent HRT use substantially reduces risk of colon cancer.
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PMID:Hormone replacement therapy and colon cancer among members of a health maintenance organization. 1040 82

Colorectal cancer is the third leading cause of cancer death in women. Studies on the potential protective effect of postmenopausal hormone replacement on the incidence of colon cancer have been contradictory. To attempt to clarify the potential protective effect of hormone replacement therapy (HRT), an English-language key word (KW) search of MEDLINE, up to August 1999, was performed for KW colon cancer or colorectal adenoma or colon adenoma or adenomatous polyp and KW estrogen replacement or hormone replacement. Additional references were obtained from reading of the reference lists. Thirty-five studies, including 3 meta-analyses, were found. Of these, 23 suggested any degree of protective effect of HRT, 11 reported neutral results, and 1 reported negative impact of hormone replacement. The single prospective randomized controlled trial included small numbers of inpatients taking high-dose estrogen. However, studies did not uniformly specify hormone type, dose, duration, and potential differential effects on right and left colon. Estrogen and progesterone effects were not often considered separately. Many studies had inadequate control of confounders, for example, family history of colon cancer or indication for endoscopy. Therefore, although the majority of studies, especially more rigorously designed recent studies, support the conclusion that postmenopausal estrogen replacement therapy (ERT) has a protective effect against colon adenomas and colon cancer, methodological limitations preclude practical application of study results at present. Prospective studies are needed to confirm the existence and degree of protective effect, as well as to specify the mechanism of protection.
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PMID:Estrogen replacement therapy and colon cancer: a clinical review. 1059 28

Epidemiological studies suggest that estrogen prevents neoplastic transformation in the intestinal mucosa. Estrogen was shown to increase the expression of vitamin D receptors (VDR) in a variety of tissues. 1,25-Dihydroxyvitamin D [1,25-(OH)2D] and several of its analogues are known as potent antineoplastic and prodifferentiative in many cell types, including colon-derived cells. The present study was designed to examine the effect of estradiol (E2) on dimethylhydrazine (DMH)-induced colon cancer in rats, and the possibility that E2 may exert its protective effect on the colon through modulation of the vitamin D-endocrine system. The in vivo effect of E2 on DMH-induced colorectal cancer was studied in four groups of ovariectomized female rats: (I) untreated control, (II) E2 treated, (III) DMH treated, and (IV) combined E2 and DMH treated. Significantly higher uterine weights and higher colonic estrogen receptor content confirmed the effectiveness of ovariectomy and E2 replacement. The number of malignant tumors in group IV was 2.3+/-1.1 (mean +/- SE) per rat, compared with 8.1+/-1.9 in group III (P < 0.001). Exposure to estrogen was associated with a marked increase in VDR mRNA content and VDR protein expression in the normal colonic mucosa. In tumor extracts VDR protein expression was considerably lower compared with normal mucosa. Estrogen treatment did not affect serum levels of 25(OH)D, 1,25(OH)2D, and PTH. Significant CpG island methylation in the VDR gene was observed in colonic tissue DNA harvested from rats treated with DMH, but not in colonic mucosae from rats treated with DMH + E2. The highest frequency of CpG methylation in the VDR gene was detected in DNA extracted from cancer tissue rims. In summary, the protective effect of estrogen against chemically induced colonic carcinogenesis is associated with reduced methylation of the VDR gene and with upregulation of both VDR gene transcription and protein expression. We suggest that estrogen may interfere with the process of CpG DNA methylation in the colonic mucosa to prevent silencing of the VDR gene. Increased VDR activity could be one of the mechanisms by which estrogen protects against neoplastic transformation in the colon.
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PMID:The protective effect of estrogen against chemically induced murine colon carcinogenesis is associated with decreased CpG island methylation and increased mRNA and protein expression of the colonic vitamin D receptor. 1069 Oct 27

There is preliminary evidence that polymorphism of apolipoprotein E (apoE, protein; APOE, gene), one of the key regulatory proteins in cholesterol metabolism, influences the pathobiology of carcinoma of the colon, prostate and breast and also primary tumours of the brain. This study was designed to determine whether APOE polymorphism is related to variation in the rate of tumour cell proliferation and clinical outcome in carcinoma of the breast. One hundred and eleven infiltrating ductal carcinomas, for which follow up data were available, were included in the study. Estrogen and progesterone receptor status (ER, PR) cell proliferation index (MIB- 1) and APOE genotypes were determined from paraffin-embedded tissue by standard methods. Positive correlations were found between grade and tumour size, grade and presence of metastasis, grade and MIB-1 expression, as well as between ER and PR. Survival correlated inversely with tumour size and the presence of positive lymph nodes. Both steroid receptors correlated inversely with MIB- 1 expression. PR positive status also correlated inversely with high histological grade and presence of lymph node metastases. APOE allele frequencies resembled those of the general population. No significant associations were found between possession of either APOE epsilon2 or epsilon4 alleles and the parameters investigated. Although there is evidence to suggest that APOE epsilon4 may predispose to the development of carcinoma of the breast our data do not support the hypothesis that APOE genotype influences the rate of tumour cell proliferation or the clinical course.
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PMID:Apolipoprotein E polymorphism and breast carcinoma: correlation with cell proliferation indices and clinical outcome. 1111 53

Estrogen replacement therapy either with (HRT) or without (ERT) accompanying progesterone is routinely offered to well women at the time of menopause, in order to relieve vasomotor symptoms, (hot flashes), reduce urogenital atrophy and reduce the risks of cardiovascular disease, osteoporosis and perhaps colon cancer and Alzheimer's disease. It is generally felt however, that women with a previous diagnosis of breast cancer are not suitable candidates for such therapy since either estrogen or progesterone may be associated with an increased risk of cancer recurrence. There are however, a variety of approaches to menopausal therapy in such women. A careful history must first be taken in order to identify the symptoms or conditions of concern. Vasomotor symptoms can be reduced by the use of other medications such as the antidepressant venlafaxine (Effexor). Estring, a vaginal estrogen ring can be used to reduce genitourinary symptoms, with little systemic estrogen absorption. Osteoporosis can be prevented or treated with calcium supplements, exercise, improved diet, bisphosphonates and/or selective estrogen receptor modulators (SERMs) while cardiovascular risk can be reduced by diet and exercise, as well as the appropriate use of lipid lowering and antihypertensive medications.
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PMID:The role of hormone replacement therapy in women with a previous diagnosis of breast cancer and a review of possible alternatives. 1133 40

Estrogen used alone (estrogen replacement therapy [ERT]) or with the addition of progesterone (hormone replacement therapy [HRT]) is known to be effective in reducing menopausal symptoms including hot flashes, vaginal dryness and urinary symptoms. It has been traditionally contraindicated, however, in women with a previous diagnosis of breast cancer because of fear that it may increase the risk of recurrence. There are considerable basic scientific data but little methodologically strong observational data and none from randomized studies concerning the use of ERT in women with a prior diagnosis of breast cancer. From our knowledge of the physiology of breast cancer, however, estrogen and/or progestational agents should be used with caution in women with a previous diagnosis of breast cancer. There are currently many alternatives to ERT/HRT in the prevention of menopausal symptoms such as vitamin E, clonidine and selective serotonin reuptake inhibitor antidepressants such as venlafaxine. There are also a variety of other approaches to the prevention of osteoporosis and cardiovascular disease including bisphosphonates, diet, and exercise; and diet, exercise, and statins, respectively. Other suggested beneficial effects of estrogen such as colon cancer prevention can be approached by the use of aspirin or the non-steroidals. Several trials of ERT/HRT used for 2 years versus no therapy in menopausal women with a previous diagnosis of breast cancer are ongoing in Europe and Britain, and should give us stronger data as to the role of HRT in this setting.
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PMID:Hormone replacement in women with a history of breast cancer. 1152 54

The advantages and disadvantages of hormone replacement therapy (HRT) have been debated nearly as long as the treatment has been in use, especially the relationship between HRT and risk of cancer development. It is hoped that recently published studies will shed more light on this complex issue. Several large population studies suggest that there may be a small but increased risk of developing breast cancer in HRT users, especially in estrogen and progesterone users. This risk appears most pronounced after 5 years of HRT use. Endometrial cancer, which has long been associated with unopposed estrogen use, can be successfully prevented with the addition of progestins to the HRT regimen, provided it is given for at least 10 days each month. Estrogen replacement therapy has also been shown to significantly reduce the risk for colon cancer but not rectal cancers. Finally, a large prospective study has linked HRT with an increase in ovarian cancer mortality.
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PMID:Hormone replacement therapy and cancer risk. 1155 17

Carcinoma of the colon is common and its incidence varies according to the geographical location and dietary habits. The aims of this paper are, first, to review the current epidemiological data on the incidence and mortality of colon cancer in postmenopausal women using hormone replacement therapy (HRT); second, to review the published data on the prevalence of estrogen receptors in healthy and malignant colonic tissue; and third, to examine the available evidence of gene silencing as applicable to this and other neoplastic conditions. Estrogen use confers overall protection, with a reduction in the incidence of colon adenoma and carcinoma of about 30%. Estrogen use reduces the colon cancer-related mortality. The risk of colon cancer is decreased among current and recent users of postmenopausal HRT but the molecular mechanisms involved remain unclear. Estrogen acts either on a single major transformation step in the oncogenetic process, or is involved in multiple events that avert the course of this transformation. Aberrant methylation of the CpG islands in the promoter regions of the estrogen receptor gene, as well as of other genes, is equivalent to the silencing of that gene, with the consequence of inactivation, or reduced expression, of a number of genes downstream, including tumor suppressor genes. This epigenetic mechanism, when reversed, suppresses the growth of cancer cells in vitro and in vivo. The ubiquitous distribution of the estrogen receptor genes and their isoforms, in a tissue-specific manner, opens new avenues for the understanding of cellular behavior in health and disease.
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PMID:Estrogen and colon cancer: current issues. 1197 57

Soybeans are a natural dietary source of isoflavones, which have estrogen-like properties. Therefore, it is worthwhile to consider the implications for soy of the recently published findings of the Heart and Estrogen/Progestin Replacement Study (HERS) I/II and the Women's Health Initiative (WHI). The WHI found coronary heart disease (CHD) risk to be increased in women receiving hormone replacement therapy, and both studies found increases in venous thromboembolic disease in such women. Additionally, stroke and breast cancer risk were increased in the WHI, although risk of colorectal cancer and fracture was decreased. Because research suggests that it is the combination of estrogen plus progestin, and not estrogen alone, that increases breast cancer risk, soy seems unlikely to increase risk because it has no progestin activity. Similarly, there is no evidence to suggest that soy will increase venous thromboembolic disease or stroke; however, only limited data are available in this area. There are promising data suggesting that soy may decrease CHD risk, although studies conducted thus far have examined only markers of risk and not actual CHD events. Similarly, short-term studies generally suggest that soy reduces bone loss in postmenopausal women; however, such effects have been noted primarily only at the spine, and longer-term studies are needed. Finally, very limited human research suggests that soy may decrease colon cancer risk, but this is highly speculative. The results of HERS I/II and WHI suggest that soy may have some of the advantages, but not the disadvantages, of combined hormone replacement therapy (at least with respect to the specific hormones and doses used in the HERS I/II and WHI), but that large, long-term intervention studies examining disease outcome are needed before definitive conclusions can be drawn. Nevertheless, the evidence warrants recommendations that menopausal women include soy in their diets.
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PMID:Soy foods and soybean isoflavones and menopausal health. 1255 10


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