Dietary glycaemic index, glycaemic load and endometrial and ovarian cancer risk: a systematic review and meta-analysis.

Long-term consumption of a high glycaemic index (GI) or glycaemic load (GL) diet may lead to chronic hyperinsulinaemia, which is a potential risk factor for cancer. To date, many studies have examined the association between GI, GL and cancer risk, although results have been inconsistent, therefore our objective was to conduct a systematic review of the literature. Medline and Embase were systematically searched using terms for GI, GL and cancer to identify studies published before December 2007. Random effects meta-analyses were performed for endometrial cancer, combining maximally adjusted results that compared risk for those in the highest versus the lowest category of intake. Separate analysis examined risk by body mass index categories. Five studies examining GI and/or GL intake and endometrial cancer risk were identified. Pooled effect estimates for endometrial cancer showed an increased risk for high GL consumers (RR 1.20; 95% CI: 1.06-1.37), further elevated in obese women (RR 1.54; 95% CI: 1.18-2.03). No significant associations were observed for GI. Only two studies examined ovarian cancer and therefore no meta-analysis was performed, but results indicate positive associations for GL also. A high GL, but not a high GI, diet is positively associated with the risk of endometrial cancer, particularly among obese women. © 2008 Cancer Research UK All rights reserved.

Comparative validation of c-kit exon 11 mutation analysis on cytology samples and corresponding surgical resections of gastrointestinal stromal tumours

Objective:

Dietary Carbohydrate Intake, Glycemic Index, and Glycemic Load and Endometrial Cancer Risk: A Prospective Cohort Study

Endometrial cancer risk has been directly associated with glycemic load. However, few studies have investigated this link, and the etiological role of specific dietary carbohydrate components remains unclear. Our aim was to investigate associations of carbohydrate intake, glycemic index, and glycemic load with endometrial cancer risk in the US Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Recruitment took place in 1993-2001. Over a median of 9.0 years of follow-up through 2009, 386 women developed endometrial cancer among 36,115 considered in the analysis. Dietary intakes were assessed using a 124-item diet history questionnaire. Cox proportional hazards models were applied to calculate hazard ratios and 95% confidence intervals. Significant inverse associations were detected between endometrial cancer risk and total available carbohydrate intake (hazard ratio (HR) = 0.66, 95% confidence interval (CI): 0.49, 0.90), total sugars intake (HR = 0.71, 95% CI: 0.52, 0.96), and glycemic load (HR = 0.63, 95% CI: 0.46, 0.84) when women in the highest quartile of intake were compared with those in the lowest. These inverse associations were strongest among overweight and obese women. No associations with endometrial cancer risk were observed for glycemic index or dietary fiber. Our findings contrast with previous evidence and suggest that high carbohydrate intakes and glycemic loads are protective against endometrial cancer development. Further clarification of these associations is warranted.

Expression of transketolase-like 1 protein (TKTL1) in human endometrial cancer

Malignant tumors metabolize glucose to lactate even in the presence of oxygen (aerobic glycolysis). The metabolic switch from oxidative glycolysis to non-oxidative fermentation of glucose and proteins performed by the tumor cells seems to be associated with TKTL1 and pAkt overexpression. Therefore the aim of the present study was to investigate the expression of TKTL1 and pAkt in human specimens of endometrial cancer as compared to benign endometrium. Additionally, expression of the glucose transporter GLUT1 was also investigated as aerobic glycolysis is associated with an increased need for glucose.

Perifosine inhibits growth of human experimental endometrial cancers by blockade of AKT phosphorylation

Perifosine is an orally active alkylphospholipid analog, which has shown anti-tumor activity in a variety of cancers by inhibition of AKT phosphorylation. The objective of the current study was to evaluate its efficacy in in vitro models of human endometrial cancer.

Risk factors (excluding hormone therapy) for endometrial hyperplasia: a systematic review.

Objective: To conduct a systematic review of risk factors associated with the development of Endometrial Hyperplasia (EH).

Data sources: Ovid MEDLINE, EMBASE and Web of Science databases were searched from inception to 30 June 2015.

Study eligibility: Fifteen observational studies that reported on EH risk in relation to lifestyle factors (n=14), medical history (n=11), reproductive and menstrual history (n=9) and measures of socio-economic status (n=2) were identified. Pooled relative risk estimates and corresponding 95% confidence intervals (CI) were able to be derived for EH and Body Mass Index (BMI), smoking, diabetes and hypertension, using random effects models comparing high versus low categories.

Results: The pooled relative risk for EH when comparing women with the highest versus lowest BMI was 1.82 (95% CI 1.22–2.71; n=7 studies, I2=90.4%). No significant associations were observed for EH risk for smokers compared with non-smokers (RR 0.88, 95% CI 0.66-1.17; n=3, I2=0.0%), hypertensive versus normotensive women (RR 1.51, 95% CI 0.72–3.15; n=5 studies, I2=79.1%), or diabetic versus non-diabetic women (RR 1.77, 95% CI 0.79–3.96; n=5 studies, I2=31.8%) respectively although the number of included studies was limited. There were mixed reports on the relationship between age and risk of EH. Too few studies reported on other factors to reach any conclusions in relation to EH risk.

Conclusions: A high BMI was associated with an increased risk of EH, providing additional rationale for women to maintain a normal body weight. No significant associations were detected for other factors and EH risk, however relatively few studies have been conducted and few of the available studies adequately adjusted for relevant confounders. Therefore, further aetiological studies of endometrial hyperplasia are warranted.

Selected polymorphisms in sex hormone-related genes, circulating sex hormones and risk of endometrial cancer.

BACKGROUND: The role of estrogen and progesterone in the development of endometrial cancer is well documented. Few studies have examined the association of genetic variants in sex hormone-related genes with endometrial cancer risk. METHODS: We conducted a case-control study nested within three cohorts to examine the association of endometrial cancer risk with polymorphisms in hormone-related genes among 391 cases (92% postmenopausal at diagnosis) and 712 individually-matched controls. We also examined the association of these polymorphisms with circulating levels of sex hormones and SHBG in a cross-sectional analysis including 596 healthy postmenopausal women at blood donation (controls from this nested case-control study and from a nested case-control study of breast cancer in one of the three cohorts). RESULTS: Adjusting for endometrial cancer risk factors, the A allele of rs4775936 in CYP19 was significantly associated (OR(per allele)=1.22, 95% CI=1.01-1.47, p(trend)=0.04), while the T allele of rs10046 was marginally associated with increased risk of endometrial cancer (OR(per allele)=1.20, 95% CI=0.99-1.45, p(trend)=0.06). PGR rs1042838 was also marginally associated with risk (OR(per allele)=1.25, 95% CI=0.96-1.61, p(trend)=0.09). No significant association was found for the other polymorphisms, i.e. CYP1B1 rs1800440 and rs1056836, UGT1A1 rs8175347, SHBG rs6259 and ESR1 rs2234693. Rs8175347 was significantly associated with postmenopausal levels of estradiol, free estradiol and estrone and rs6259 with SHBG and estradiol. CONCLUSION: Our findings support an association between genetic variants in CYP19, and possibly PGR, and risk of endometrial cancer.

Conceptus-mediated endometrial vascular changes during early pregnancy in mares: an anatomic, histomorphometric, and vascular endothelial growth factor receptor system immunolocalization and gene expression study

This work examined how the conceptus modulates endometrial tissue remodeling and vascular development prior to implantation in mares. A macroscopic uterine examination was completed at day 21 of pregnancy. In situ morphology revealed that the endometrium involved in encroachment is restricted to the dorsal endometrium immediately overlying the yolk sac. The amount of stromal area occupied by blood vessels and the number of endometrial glands were increased during early pregnancy. Endometrial histomorphometry as well as the endometrial mRNA abundance and immunolocalization of VEGF, VEGFR1, VEGFR2, and Ki-67 was completed at days 14 and 21 of pregnancy, at day 10 of the estrous cycle, and during estrus. No obvious differences in VEGF and VEGFR1 protein localization were detected between pregnant and cycling mares but differential staining pattern for VEGFR2 and Ki-67 was observed. VEGFR2 localized to luminal and glandular epithelium of pregnant mares, while luminal epithelium was negative in cycling mares. Ki-67 staining was weak during the luteal phase but exhibited prominent luminal epithelium staining during estrus. In pregnant mares, all endometrial layers were Ki-67 positive. Quantitative RT-PCR revealed a greater abundance of VEGF mRNA during pregnancy. VEGFR2 transcript abundance was greatest in pregnant mares on day 21. This study supports the concept that the conceptus plays an active role in directing vasculogenesis within the uterus and thereby establishing hemotrophic nutrition that supports pregnancy after implantation. Reproduction (2011) 142 593-603