The Effects of Long-Term Estrogen Administration to Women following Hysterectomy

Burch, Jane; Byrd, Benjamin F.; Vaughn, William K.

doi:10.1159/000398277

Cited by 38 publications

(4 citation statements)

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“…A pivotal role for steroidal hormones in cancer is also supported by epidemiological studies in women showing that 57 hormone replacement therapy (HRT) with estrogen reduces risk of CRC. 58-60 One possible explanation is that estrogen drives expansion of IL-10-dependent CD4+CD25+ T REG cells, 61-64 a feature of ovulation and pregnancy that minimizes maternal rejection. 65 This tolerance-based effect toward gut bacteria may serve to downregulate carcinogenic inflammation in the bowel in female animal; levels of cytokine IL-6 are generally lower than in males.…”

Section: Discussionmentioning

confidence: 99%

Unifying roles for regulatory T cells and inflammation in cancer

Erdman¹,

Rao²,

Olipitz³

et al. 2010

Intl Journal of Cancer

137

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Activities of CD4+ regulatory (TREG) cells restore immune homeostasis during chronic inflammatory disorders. Roles for TREG cells in inflammation-associated cancers, however, are paradoxical. It is widely believed that TREG function in cancer mainly to suppress protective anticancer responses. However, we demonstrate here that TREG cells also function to reduce cancer risk throughout the body by efficiently downregulating inflammation arising from the gastrointestinal (GI) tract. Building on a “hygiene hypothesis” model in which GI infections lead to changes in TREG that reduce immune-mediated diseases, here we show that gut bacteria-triggered TREG may function to inhibit cancer even in extraintestinal sites. Ability of bacteria-stimulated TREG to suppress cancer depends on interleukin (IL)-10, which serves to maintain immune homeostasis within bowel and support a protective antiinflammatory TREG phenotype. However, under proinflammatory conditions, TREG may fail to provide antiinflammatory protection and instead contribute to a T helper (Th)-17-driven procarcinogenic process; a cancer state that is reversible by downregulation of inflammation. Consequently, hygienic individuals with a weakened IL-10 and TREG-mediated inhibitory loop are highly susceptible to the carcinogenic consequences of elevated IL-6 and IL-17 and show more frequent inflammation-associated cancers. Taken together, these data unify seemingly divergent disease processes such as autoimmunity and cancer and help explain the paradox of TREG and inflammation in cancer. Enhancing protective TREG functions may promote healthful longevity and significantly reduce risk of cancer.

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Section: Discussionmentioning

confidence: 99%

Unifying roles for regulatory T cells and inflammation in cancer

Erdman¹,

Rao²,

Olipitz³

et al. 2010

Intl Journal of Cancer

137

View full text Add to dashboard Cite

show abstract

“…Studies investigating the role of exogenous estrogens have also given equivocal results (Weiss et al, 1981;Potter and McMichael, 1983;Burch et al, 1975) which may reflect variations in the use of exogenous hormones. For example, in the United States the use of oral contraceptives increased from their introduction in 1960 until 1976 and declined subsequently (Russell-Briefel et al, 1985).…”

Section: Discussionmentioning

confidence: 99%

The influence of parity and exogenous female hormones on the risk of colorectal cancer

Davis

Furner

Persky

et al. 1989

Intl Journal of Cancer

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Evidence that female sex hormones may play a role in the subsequent development of colorectal cancer has accumulated from time trends in colorectal cancer rates and from epidemiologic studies. Using data available from the Cross Cancer Institute Northern Alberta Cancer Program, the relationship of parity, exogenous hormones and colorectal cancer was evaluated. Five hundred and twenty-eight colon cancer and 192 rectal cancer cases were identified and 349 nonendocrine cancers were selected as controls. All subjects were diagnosed and interviewed between 1969 and 1973. Protective associations between previous pregnancies and colorectal cancer were found in women over age 50 at diagnosis (OR = 0.5, 95% CI = 0.3-0.9) and in women who never used exogenous hormones (OR = 0.3, 95% CI = 0.2-0.7). Results from this study provide additional support for earlier suggestions that parity may have a protective effect against the development of colorectal cancer, similar to the effects reported in the case of breast, endometrial and ovarian tumors.

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“…In humans, men are up to 70% more likely than women to suffer from colon cancer and dysregulated IL-6 (J. Lin et al 2007;Burch et al 1975). Interleukin-6 may function through activation of Stat3 phosphorylation in tumor cells, resulting in inhibition of dendritic cell maturation (Berishaj et al 2007;Menetrier-Caux et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Roles for Inflammation and Regulatory T Cells in Colon Cancer

Erdman

Poutahidis

2009

Toxicol Pathol

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Risk for developing cancer rises substantially as a result of poorly regulated inflammatory responses to pathogenic bacterial infections. Anti-inflammatory CD4+ regulatory cells (TREG) function to restore immune homeostasis during chronic inflammatory disorders. It seems logical that TREG cells would function to reduce risk of inflammation-associated cancer in the bowel by down-regulating inflammation. It is widely believed, however, that TREG function in cancer mainly to suppress protective anticancer inflammatory responses. Thus roles for inflammation, TREG cells, and gut bacteria in cancer are paradoxical and are the subject of controversy. Our accumulated data build upon the “hygiene hypothesis” model in which gastrointestinal (GI) infections lead to changes in TREG that reduce inflammation-associated diseases. Ability of TREG to inhibit or suppress cancer depends upon gut bacteria and IL-10, which serve to maintain immune balance and a protective anti-inflammatory TREG phenotype. However, under poorly regulated pro-inflammatory conditions, TREG fail to inhibit and may instead contribute to a T helper (Th)-17-driven procarcinogenic process, a cancer state that is reversible by down-regulation of inflammation and interleukin (IL)-6. Consequently, hygienic individuals with a weakened IL-10– and TREG–mediated inhibitory loop are highly susceptible to the carcinogenic consequences of elevated inflammation and show more frequent inflammation-associated cancers. Taken together, these data help explain the paradox of inflammation and TREG in cancer and indicate that targeted stimulation of TREG may promote health and significantly reduce risk of cancer.

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The Effects of Long-Term Estrogen Administration to Women following Hysterectomy

Cited by 38 publications

References 0 publications

Unifying roles for regulatory T cells and inflammation in cancer

Unifying roles for regulatory T cells and inflammation in cancer

The influence of parity and exogenous female hormones on the risk of colorectal cancer

Roles for Inflammation and Regulatory T Cells in Colon Cancer

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