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Abstract
Background and Aims: Obesity is a known risk factor for endometrial cancer (EC), but connections of this tumor with different obesity phenotypes (namely ‘standard’, SO /characterized by insulin resistance / or ‘metabolically healthy’, MHO) were studied so far extremely rarely. The task of this study was to evaluate the role of genetic and genotoxic component in this issue.
Methods and Results: In 70-110 (depending on the method used) mainly postmenopausal EC patients was found that: a) The genotypes of leptin receptor (Gln223Arg) or FTO, fat mass and obesity associated (rs 9939609) genes are discovered in SO and MHO groups with different frequency; b) No differences exist between EC patients with SO or MHO in regard of such parameters like the tail moment and tail DNA% in comets of mononuclear cells, as well as in serum level of 8-hydroxy-2deoxyguanosine (8-OHdG) and in mononuclears’ telomeres length; c) In patients with EC combined with SO, TT genotype of the FTO gene correlates with a more advanced clinical stage of the disease, while comets characteristics - with a worse tumor differentiation; d) In EC patients with MHO, poorly differentiated carcinomas are combined more often with genotype AA of leptin receptor gene presence and with a trend to higher 8-OHdG blood level, while a more advanced clinical stage and (at the same time) a better tumor differentiation -with telomeres length.
Conclusions: The parameters that delineate a genome state and a degree of systemic DNA damage, can differ by their characteristics in EC patients with SO and MHO and not rarely are associated in various ways with clinical and morphological features of the tumor process in the two studied obesity phenotypes. Subsequently, there are grounds to study these issues taking into account the renovated classification of molecular biological types of endometrial cancer.
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