Steroid receptors in dimethylhydrazine-induced colon carcinogenesis

Odagiri, Emi; Jibiki, Kazuko; Kato, You; Nakamura, Shintaro; Oda, Sen-ichi; Demura, Reiko; Demura, Hiroshi

doi:10.1002/1097-0142(19851201)56:11<2627::aid-cncr2820561116>3.0.co;2-j

Cited by 15 publications

(6 citation statements)

References 18 publications

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“…Indeed, males treated with estradiol exhibit significantly less tumors than untreated rats in some chemical mutagen-induced models of colon cancer. 25,26 Alternatively, ERb may be a more important player in colon epithelial cell homeostasis in females than in males. This is supported by slightly higher ERb levels in normal mucosa in women than in normal mucosa in men.…”

Section: Discussionmentioning

confidence: 99%

Estrogen receptor β deficiency enhances small intestinal tumorigenesis in Apc^Min/+ mice

Giroux

Lemay

Bernatchez

et al. 2008

Intl Journal of Cancer

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Clinical evidence suggests that estradiol replacement therapy reduces colon cancer risk in ‘post’menopausal women. In colon epithelial cells, the estrogen receptor β (ERβ) is the predominant ER subtype and is thought to mediate the genomic effect of estrogens. The first aim of this study was to investigate the consequence of ERβ deficiency on intestinal tumorigenesis in the ApcMin/+ mouse model. Furthermore, to explore the biological mechanisms by which estrogens may influence the pathogenesis of colorectal cancer, we performed gene expression profiles in colonocytes from ovariectomized wild‐type (WT) vs. ERβ−/− mice, treated with estradiol (E2) or vehicle. Specifically in female, ERβ deficiency was found to be associated with higher adenoma multiplicity in the small intestine, but not in the colon. Furthermore, tumors from ERβ−/−ApcMin/+ female mice were on average significantly larger than those from control ApcMin/+ mice. Higher steady‐state proliferation in epithelial cells of the jejunum and colon from ERβ−/−ApcMin/+ vs. ApcMin/+ female mice was confirmed by BrdU incorporation assay. Interestingly, functional categorization of microarray results revealed the TGFβ signaling pathway to be modulated in colonocytes, especially for the WT + E2 vs. WT + Vehicle and the ERβ−/− + E2 vs. WT + E2 comparisons. Using quantitative PCR analysis, we observed transcripts from ligands of the TGFβ pathway to be upregulated in colonocytes from E2‐treated WT and ERβ−/− mice and downregulated in ERβ‐deficient mice, mostly in an E2‐independent manner. Therefore, our results demonstrate that ERβ deficiency enhances small intestinal tumorigenesis and suggest that modulation of the TGFβ signaling pathway could contribute to the protective role of estrogens on intestinal tumorigenesis. © 2008 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Estrogen receptor β deficiency enhances small intestinal tumorigenesis in Apc^Min/+ mice

Giroux

Lemay

Bernatchez

et al. 2008

Intl Journal of Cancer

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“…In these analyses, covariates included age (time to event variable); body mass index (kg/m 2 ) (quintiles); menopausal status (pre‐, peri‐, postmenopausal), pack‐years of smoking (never smoked + 5 levels for smokers); and education (3 levels). Addition of indicator variables for screening center1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and randomization group in the original clinical trial (intervention/usual care) did not affect the risk estimates, and therefore these variables were omitted. The second stage of the analysis was restricted to the dietary cohort.…”

Section: Methodsmentioning

confidence: 99%

“…reported that in individuals without colonic tumors, methylation of the estrogen receptor increases with age, and that in individuals with colonic tumors, estrogen receptor methylation is almost universally present, suggesting that the estrogen receptor may act as a tumor suppressor. In addition, estradiol has been shown to inhibit chemically‐induced murine colon carcinogenesis,8 and in rats treated with dimethylhydrazine, the colon tumor yield is higher in males compared to females 9…”

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Oral contraceptive use, hormone replacement therapy, reproductive history and risk of colorectal cancer in women

Kabat

Miller

Rohan

2007

Intl Journal of Cancer

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Evidence from epidemiologic studies suggests a possible role of exogenous and endogenous hormones in colorectal carcinogenesis in women. However, with respect to exogenous hormones, in contrast to hormone replacement therapy, few cohort studies have examined oral contraceptive use in relation to colorectal cancer risk. We used data from a large cohort study of Canadian women enrolled in a randomized controlled trial of breast cancer screening to assess the association of oral contraceptive use, hormone replacement therapy and reproductive factors with risk of colorectal cancer, overall and by subsite within the colorectum. Cancer incidence and mortality were ascertained by linkage to national databases. Among 89,835 women aged 40-59 at enrollment and followed for an average of 16.4 years, we identified 1,142 incident colorectal cancer cases. Proportional hazards models were used to estimate the associations between the exposures of interest and risk of colorectal cancer. Ever use of oral contraceptives at baseline was associated with a modest reduction in the risk of colorectal cancer (hazard ratio 0.83, 95% confidence interval 0.73-0.94), with similar effects for different subsites within the colorectum. No trend was seen in the hazard ratios with increasing duration of oral contraceptive use. No associations were seen with use of hormone replacement therapy (ever use or duration of use) or reproductive factors. Our results are suggestive of an inverse association between oral contraceptive use and colorectal carcinogenesis. However, given the lack of a dose-response relationship and the potential for confounding, studies with more complete assessment of exogenous hormone use throughout the life course are needed to clarify this association. ' 2007 Wiley-Liss, Inc.Key words: colorectal neoplasms; cohort study; oral contraceptive use; hormone replacement therapy; reproductive factorsIn virtually every region of the world, incidence rates of colorectal cancer are higher in men compared to women for a given age. 1 Early etiological studies indicated a correlation between colorectal cancer and breast cancer rates and elevated colon cancer rates in nuns. 2 These observations led McMichael and Potter 3 to postulate that endogenous and/or exogenous steroid hormone exposure may protect against colon cancer.Experimental studies indicate that estrogens may play a protective role in colorectal carcinogenesis either indirectly by reducing secondary bile acids and insulin-like growth factor-I or directly by regulating cell growth in the colonic epithelium and inhibiting cell proliferation of colorectal tumors by binding to the estrogen receptor. 4,5 In cultured colon cancer cells, methylation-associated loss of expression of the estrogen receptor gene results in deregulated growth. 6,7 Issa et al. 7 reported that in individuals without colonic tumors, methylation of the estrogen receptor increases with age, and that in individuals with colonic tumors, estrogen receptor methylation is almost universally present, suggesting ...

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“…(5)(6)(7) In an experimental study of rats, there is also a greater preponderance of colon cancer in men compared with women. (8) In addition, estradiol has been shown to inhibit chemically-induced murine colon carcinogenesis. (9) The recent Women's Health Initiative trial reported a connection between hormonal status and colorectal cancer risk, where postmenopausal hormone use (estrogen-plus-progestin) is associated with a 40% reduction in colorectal cancer risk, (10) further suggesting possible protective effects of estrogen and/ or progesterone in the development of colorectal cancer.…”

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confidence: 99%

Higher parity and earlier age at first birth are associated with lower risk of death from colon cancer

Kuo

et al. 2012

Cancer Science

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This study was undertaken to examine whether there is an association between parity and age at first birth and risk of colon cancer. The study cohort consisted of 1 292 462 women who had a first and singleton childbirth between 1978 and 1987. We tracked each woman from the time of their first childbirth to December 31, 2009, and their vital status was ascertained by linking records with the computerized mortality database. We used the Cox proportional hazards model with time-dependent covariates to estimate the hazard ratios (HR) of death from colon cancer associated with parity and age at first birth. We limited eligible colon cancer deaths to those who were 45 years old or more to exclude possible heredity colon cancer cases, which usually occur at an early age. There were 670 colon cancer deaths during 34 980 246 person-years of follow-up. The colon cancer death rate was 1.96 cases per 100 000 person-years. The adjusted HR was 2.76 (95% CI = 1.60-4.75) for women who gave birth between 20 and 24 years and 7.35 (95% CI = 4.28-12.62) for women who gave birth after 24 years of age when compared with women who gave birth at younger than 20 years. A rising risk of colon cancer was seen with increasing age at first birth. The adjusted HR were 0.81 (95% CI = 0.65-1.02) among women with two live births, 0.93 (95% CI = 0.74-1.18) among women with three live births and 0.72 (95% CI = 0.51-1.00) for women with four or more births when compared with women who had given birth to only one child. The present study provides evidence that reproductive factors (parity and early age at first birth) may confer a protective effect on the risk of colon cancer. (Cancer Sci 2012; 103: 1553-1557 I n Taiwan, colorectal cancer is the third leading cause of cancer death for men and women.(1) In 2010, The age-adjusted death rate for colorectal cancer was 23.4 per 100 000 among men and 17.0 per 100 000 among women. There is substantial geographic variation in colorectal cancer death within the country.Men tend to have a higher incidence of colon cancer than women of similar age.(2) An excess not only of some reproductive cancers but also of colon cancer was observed among nuns.(3) It has been hypothesized that sex hormones play a role in the protective effect against colon cancer.(4) The influence of sex hormones on colon cancer risk is supported by the presence of estrogen receptors in the normal colonic epithelium and neoplastic colonic tissue.(5-7) In an experimental study of rats, there is also a greater preponderance of colon cancer in men compared with women.(8) In addition, estradiol has been shown to inhibit chemically-induced murine colon carcinogenesis.(9) The recent Women's Health Initiative trial reported a connection between hormonal status and colorectal cancer risk, where postmenopausal hormone use (estrogen-plus-progestin) is associated with a 40% reduction in colorectal cancer risk, (10) further suggesting possible protective effects of estrogen and/ or progesterone in the development of colorectal cancer. However, two pro...

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Steroid receptors in dimethylhydrazine-induced colon carcinogenesis

Cited by 15 publications

References 18 publications

Estrogen receptor β deficiency enhances small intestinal tumorigenesis in Apc^Min/+ mice

Estrogen receptor β deficiency enhances small intestinal tumorigenesis in Apc^Min/+ mice

Oral contraceptive use, hormone replacement therapy, reproductive history and risk of colorectal cancer in women

Higher parity and earlier age at first birth are associated with lower risk of death from colon cancer

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Steroid receptors in dimethylhydrazine-induced colon carcinogenesis

Cited by 15 publications

References 18 publications

Estrogen receptor β deficiency enhances small intestinal tumorigenesis in ApcMin/+ mice

Estrogen receptor β deficiency enhances small intestinal tumorigenesis in ApcMin/+ mice

Oral contraceptive use, hormone replacement therapy, reproductive history and risk of colorectal cancer in women

Higher parity and earlier age at first birth are associated with lower risk of death from colon cancer

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Estrogen receptor β deficiency enhances small intestinal tumorigenesis in Apc^Min/+ mice

Estrogen receptor β deficiency enhances small intestinal tumorigenesis in Apc^Min/+ mice