Dataset Information

Insulin/IGF and sex hormone axes in human endometrium and associations with endometrial cancer risk factors.

ABSTRACT:

Purpose

Experimental and observational data link insulin, insulin-like growth factor (IGF), and estrogens to endometrial tumorigenesis. However, there are limited data regarding insulin/IGF and sex hormone axes protein and gene expression in normal endometrial tissues, and very few studies have examined the impact of endometrial cancer risk factors on endometrial tissue biology.

Methods

We evaluated endometrial tissues from 77 premenopausal and 30 postmenopausal women who underwent hysterectomy for benign indications and had provided epidemiological data. Endometrial tissue mRNA and protein levels were measured using quantitative real-time PCR and immunohistochemistry, respectively.

Results

In postmenopausal women, we observed higher levels of phosphorylated IGF-I/insulin receptor (pIGF1R/pIR) in diabetic versus non-diabetic women (p value =0.02), while women who reported regular nonsteroidal anti-inflammatory drug use versus no use had higher levels of insulin and progesterone receptors (both p values ?0.03). We also noted differences in pIGF1R/pIR staining with OC use (postmenopausal women only), and the proportion of estrogen receptor-positive tissues varied by the number of live births and PTEN status (premenopausal only) (p values ?0.04). Compared to premenopausal proliferative phase women, postmenopausal women exhibited lower mRNA levels of IGF1, but higher IGFBP1 and IGFBP3 expression (all p values ?0.004), and higher protein levels of the receptors for estrogen, insulin, and IGF-I (all p values ?0.02). Conversely, pIGF1R/pIR levels were higher in premenopausal proliferative phase versus postmenopausal endometrium (p value =0.01).

Conclusions

These results highlight links between endometrial cancer risk factors and mechanistic factors that may contribute to early events in the multistage process of endometrial carcinogenesis.

SUBMITTER: Merritt MA

PROVIDER: S-EPMC4870288 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Publications

Insulin/IGF and sex hormone axes in human endometrium and associations with endometrial cancer risk factors.

Merritt Melissa A MA Strickler Howard D HD Einstein Mark H MH Yang Hannah P HP Sherman Mark E ME Wentzensen Nicolas N Brouwer-Visser Jurriaan J Cossio Maria Jose MJ Whitney Kathleen D KD Yu Herbert H Gunter Marc J MJ Huang Gloria S GS

Cancer causes & control : CCC 20160428 6

<h4>Purpose</h4>Experimental and observational data link insulin, insulin-like growth factor (IGF), and estrogens to endometrial tumorigenesis. However, there are limited data regarding insulin/IGF and sex hormone axes protein and gene expression in normal endometrial tissues, and very few studies have examined the impact of endometrial cancer risk factors on endometrial tissue biology.<h4>Methods</h4>We evaluated endometrial tissues from 77 premenopausal and 30 postmenopausal women who underwen ...[more]

PMID: 27125830

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Project description:Paradoxically, a breast cancer risk reduction with conjugated equine estrogens (CEE) and a risk elevation with CEE plus medroxyprogesterone acetate (CEE?+?MPA) were observed in the Women's Health Initiative (WHI) randomized controlled trials. The effects of hormone therapy on serum sex hormone levels, and on the association between baseline sex hormones and disease risk, may help explain these divergent breast cancer findings.Serum sex hormone concentrations were measured for 348 breast cancer cases in the CEE?+?MPA trial and for 235 cases in the CEE trial along with corresponding pair-matched controls, nested within the WHI trials of healthy postmenopausal women. Association and mediation analyses, to examine the extent to which sex hormone levels and changes can explain the breast cancer findings, were conducted using logistic regression.Following CEE treatment, breast cancer risk was associated with higher concentrations of baseline serum estrogens, and with lower concentrations of sex hormone binding globulin. However, following CEE?+?MPA, there was no association of breast cancer risk with baseline sex hormone levels. The sex hormone changes from baseline to year 1 provided an explanation for much of the reduced breast cancer risk with CEE. Specifically, the treatment odds ratio (95% confidence interval) increased from 0.71 (0.43, 1.15) to 0.92 (0.41, 2.09) when the year 1 measures were included in the logistic regression analysis. In comparison, the CEE?+?MPA odds ratio was essentially unchanged when these year 1 measures were included.Breast cancer risk remains low following CEE use among women having favorable baseline sex hormone profiles, but CEE?+?MPA evidently produces a breast cancer risk for all women similar to that for women having an unfavorable baseline sex hormone profile. These patterns could reflect breast ductal epithelial cell stimulation by CEE?+?MPA that is substantially avoided with CEE, in conjunction with relatively more favorable effects of either regimen following a sustained period of estrogen deprivation. These findings may have implications for other hormone therapy formulations and routes of delivery.clinicaltrials.gov identifier: NCT00000611.

Dataset Information

Insulin/IGF and sex hormone axes in human endometrium and associations with endometrial cancer risk factors.

Purpose

Methods

Results

Conclusions

Publications

Insulin/IGF and sex hormone axes in human endometrium and associations with endometrial cancer risk factors.

Similar Datasets

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