THE INFLUENCE OF DIABETES-ASSOCIATED FACTORS OF ONCOGENESIS ON THE RISK OF BREAST AND ENDOMETRIAL CANCER AND ON THE SURVIVAL OF WOMEN WITH THIS CANCER

Abstract

Introduction. Patients with type 2 diabetes mellitus (T2D) have an increased risk of cancer of different localizations. Identification and correction of diabetes-associated factors of oncogenesis can be important in cancer prevention. The aim of the study. To investigate the influence of diabetes-associated factors of oncogenesis on the formation of the risk of breast cancer (BC) and endometrial cancer (EC), as well as on the survival of women with the indicated localization of cancer, and to develop a method of calculating the predicted risk of BC and EC in women with T2D. Materials and methods. The study includes the results of a retrospective epidemiological analysis of cancer cases in patients, residents of Ivano-Frankivsk region with T2D during 2012-2016, with an analysis of 5-year survival of patients. Statistical processing of the results was conducted using STATISTIKA-12 (StatSoft Inc., USA). The impact of the pathogenetic factors of T2D on the development of BC and EC was evaluated through multifactorial analysis and ROC-analysis in the Medcalc v.19.1.6 program. The coefficient of predicted cancer risk was determined using mathematical modelling and a logistic regression equation. Kaplan-Meier cumulative survival analysis and Cox-Mantel Test were used to assess patient survival. Results. BC and EC were most often diagnosed in women of postmenopausal age, with obesity, with a duration of T2D > 5 years, on combined antidiabetic therapy. Among women with BC, who take secretagogues 67% had obesity and 24% were overweight, with EC – 54% and 27% respectively. A new method to calculate the predicted risk of BC and EC (Y) in women with T2D has been introduced. The accuracy of the mathematical model for calculating the Y index is 76.24%. It was proved that coefficient Y increases in women with obesity (p<0.001), duration of T2D > 5 years (p<0.001), on combined therapy with non-secretagogues and secretagogues (p<0.05). It was found that T2D increases the risk of death within 1 year in women with both types of cancer (p<0.05). A worse 5-year survival rate was found in women with EC stage I treated with drugs that increase blood insulin levels (p<0.05), as well as in women with EC stage II with HbA1c > 8.0% (p<0.05). Conclusions. Obesity, duration of diabetes > 5 years, and use of secretagogues in obesity increase the risk of breast and endometrial cancer in women with T2D. The use of antidiabetic drugs that contribute to iatrogenic hyperinsulinemia may negatively affect survival in obese women with breast and endometrial cancer, both by increasing the risk of cardiovascular events and by hyperactivating insulin signaling. Decompensation of diabetes reduces the 5-year survival of patients with breast cancer and endometrial cancer. Detection of a predicted high-grade cancer risk (p = 0.7-1.0) may be an indication for correction of factors of oncogenesis and cancer screening in women with T2D.