The Associations between Metalloestrogens, GSTP1, and SLC11A2 Polymorphism and the Risk of Endometrial Cancer.

BACKGROUND

The incidence of endometrial cancer (EC) is still rising. Numerous risk factors including patient characteristics and molecular instability have been identified for EC. The presence of specific molecular markers allows specific diagnostic and prognostic approaches. Several single nucleotide polymorphisms (SNPs) have been identified to influence endometrial cancer risk. Metalloestrogens are metal ions which can mimic estrogen activity; however, their role in uterine pathologies remains unknown. This study aimed to investigate total blood trace elements levels and evaluate the distribution of selected genotypes in GSTP1 and SLC11A2 genes.

METHODS

This retrospective case-control analysis was carried out in peripheral blood samples of 110 women with endometrial cancer (EC; = 21), uterine fibroma ( = 25), endometrial polyp ( = 48), and normal endometrium ( = 16). Analysis included measurement of metals and phosphor in serum, and of genetic polymorphisms in GST (rs1695) and SLC11A2 (rs224589) in DNA from white blood cells. Serum trace elements were measured using ICP-OES spectrometry. SNPs were identified using Taq Man real-time PCR genotyping assays.

RESULTS

The study confirmed higher age (OR 2.19, 95% CI 1.69-2.24), post-menopausal status (OR 1.89, 95% CI 1.36-1.94), and diabetes type 2 (OR 1.54; 95% CI 0.97-1.72) as independent risk factors for EC. We also found a high level of Cd (OR 1.49; 95% CI 1.31-1.63) and a low level of Co (OR 0.76; 95% CI 0.53-0.59) to be independent risk factors of EC. None of the tested polymorphisms of GSTP1 and SLC11A2 were associated with EC risk. However, high Cd (OR 1.21, 95% CI 1.15-1.29) and Ni (OR 1.07, 95% CI 1.05-1.18) serum levels were significantly associated with a SLC1A2 TG genotype, and high Cd levels with GSTP1 (OR 1.05, 95% CI 1.01-1.13).