Molecular aspects of the link between obesity and endometrial cancer.

Ellis, Patricia Elizabeth

Abstract

Five percent of all cancers in postmenopausal women are attributable to being overweight and the incidence rises to 51% in women with endometrial cancer (EC). EC patients that are obese tend to have a poorer outcome, shorter survival rates and more co-morbidities than their non-obese counterparts. However, the role of excess adipose tissue in increasing cancer risk is not well understood. More specifically, the exact role of intracellular signalling factors within adipose tissue, in the development of endometrial cancer, is still unclear. This project aimed to partially address this lack of understanding by carrying out a systematic review / meta-analysis of primary studies related to the role of circulating adipokines and inflammatory molecules in EC. Cochrane Central Register of Controlled Trials (CENTRAL), Cinahl, Web of Science, Medline and Embase databases were searched using key words: endometrial cancer, obesity, adiponectin, leptin, interleukin-6 (IL-6), tumour necrosis factor alpha (TNFα), insulin-like growth factor I (IGF-I), and insulin-like growth factor II (IGF-II). Obese, overweight and normal weight women with EC (n=25 including one patient with endometrial hyperplasia) were recruited into a small clinical study and blood samples taken for analysis of the above-mentioned inflammatory markers and adipokines. Results from the meta-analysis suggest that participants with circulating adiponectin levels in the highest tertile had 0.51 times decreased EC risk compared to women with levels in the lowest tertile (summary of odds ratio (SOR): 0.51, 95% confidence interval (CI): 0.38-0.069, p < 0.00001). Women with circulating leptin concentrations in the highest tertile had 2.19 times increased EC risk compared to the women with concentrations in the lowest tertile (SOR: 2.19, 95% CI: 1.45-3.30, p < 0.0002). Pooled results demonstrated no significant differences in TNFα and IL-6 circulating levels between participants with the highest levels compared to the lowest levels. In this small clinical study, higher concentrations of leptin, TNFα, IL-6, IGF-I and IGF-II were observed in obese patients with EC compared to overweight and normal weight patients with EC. Adipocytokines may act synergistically to increase the risk and development of EC in women with different BMI.

Citation

ELLIS, P.E. 2020. Molecular aspects of the link between obesity and endometrial cancer. Robert Gordon University, MRes thesis. Hosted on OpenAIR [online]. Available from: https://openair.rgu.ac.uk

• Thesis Type: Thesis
• Deposit Date: Mar 8, 2021
• Publicly Available Date: Mar 8, 2021
• Keywords: Endometrial cancer; Obesity; Adipokines; Adiponectin; Leptin; Tumour necrosis factor alpha (TNFα); Interleukin-6 (IL-6); Insulin-like growth factor
• Public URL: https://rgu-repository.worktribe.com/output/1254512
• Award Date: Jul 31, 2020