A Narrative Review of the Role of Diet and Lifestyle Factors in the Development and Prevention of Endometrial Cancer

Abstract

Endometrial cancer is the most common cancer affecting the reproductive organs of women living in higher-income countries. Apart from hormonal influences and genetic predisposition, obesity and metabolic syndrome are increasingly recognised as major factors in endometrial cancer risk, due to changes in lifestyle and diet, whereby high glycaemic index and lipid deposition are prevalent. This is especially true in countries where micronutrients, such as vitamins and minerals are exchanged for high calorific diets and a sedentary lifestyle. In this review, we will survey the currently known lifestyle factors, dietary requirements and hormonal changes that increase an individual's risk for endometrial cancer and discuss their relevance for clinical management. We also examine the evidence that everyday factors and clinical interventions have on reducing that risk, such that informed healthy choices can be made. In this narrative review, we thus summarise the dietary and lifestyle factors that promote and prevent the incidence of endometrial cancer.

Keywords: diabetes; diet; endometrial cancer; hormones; lipids; melatonin; minerals; nutrients; obesity; vitamins.

Figure 1

Epidemiological, genetic, clinical, lifestyle and dietary risk factors for the development of endometrial cancers. Two distinct pathways are depicted in which non-modifiable and modifiable risk factors are listed. * Nulliparity is included as modifiable risk factor because pregnancy can reduce the risk of EC development. It could also conceivably be included as a non-modifiable risk factor, since some women are unable to conceive. ^ψ Familial genetic mutations are also risk factors for EC and are associated with Lynch syndrome, Cowden’s syndrome, and Polymerase proof-reading polyposis (see Figure 5).

Figure 2

Estimated crude incidence rate for endometrial cancer (all ages; 0–85+) in 2018, based on different regions of the world. Data are shown from lowest incidence rate to highest incidence rates with Northern Europe highlighted with the solid bar. Adapted from [40].

Figure 3

Overview of the molecular classification systems for EC. Panel (A) indicates that genetic mutations are related to the four genomic classes of EC, defined as the Cancer Genome Atlas (TCGA) classification through POLE mutations, which are ultramutated (UM); Multisatellite (MSI) instability events, which are hypermutated events (HM); or are copy number low (CNL) or copy number high (CNH). The relationships between these four genomic classes and patient prognosis, pathognomic factors and other gene alterations is depicted. In Panel (B), the distributions of these TCGA genomic classes is shown as a percentage of the tumours based on the trialistic grading system and with respect the Type 2 serous EC. The % of tumours that have ultramutated POLE mutations (UM); hypermutated MSI (HM); or are copy number low (CNL) or copy number high (CNH) are shown. Where the bar is not visible, the data indicate that none of those tumours have that event associated with them. Data are adapted from [70,71].

Figure 4

Overview of endometrial cancer origin and development. A schematic representations of the development of and progression of endometrioid (Type 1) EC (left side) and of non-endometrioid serous (Type 2) EC (right side) from their respective normal and atrophic endometrial glandular epithelial cells. During initiation, PTEN or TP53 gene mutations (early events in the aetiopathology of many endometrioid and serous ECs) and other genetic aberrations result in the formation of precursor lesions (complex atypical hyperplasia and serous intratumoural intraepithelial carcinoma, respectively). The epithelial cells that accumulate mutations and genetic alterations are coloured. Sometimes, carcinomas (particularly high-grade tumours) undergo epithelial to mesenchymal cell transition (EMT), giving rise to uterine carcinosarcomas, which as dualistic tumours consist of both epithelial carcinoma cells and sarcoma cells (dark blue and green cells and ovoid blue cells, respectively). Data are adapted from [70,71].

Figure 5

Hereditary syndromes manifesting as increased risk of developing EC. Each of these diseases is inherited in an autosomal dominant manner and each is a non-modifiable risk factor for the development of EC. The mismatch genes, MutL Homolog 1 (MLH1), MutS Homolog 2 (MSH2), MutS Homolog 6 (MSH6) and PMS1 Homolog 2, Mismatch Repair System Component (PMS2) are all component parts of the post-replicative DNA mismatch repair system (MMR) that coordinately repairs double stranded DNA errors. Mutations of these genes prevents DNA repair. * A hamartoma is a tumour-like, non-neoplastic disordered proliferation of mature tissue.