Statistics based on GLOBOCAN 2022 (estimates from the International Agency for Research on Cancer) indicates that the number of new cases of malignant neoplasms (MNs) in the world has reached 20 million [1]. It is estimated that approximately one in five men or women develops MN during their lifetime, and about one in nine men and one in twelve women die from it [1]. Projections indicate that new MN cases will surpass 35 million in 2050, representing a 77% increase over 2022. Demographic transition is a key factor determining the extent of cancer spread: in 2022, the global population was about 8 billion people, and by 2050 it will reach 9.7 billion [1]. Malignant neoplasms of the endometrium (uterine corpus) are the sixth most frequently diagnosed cancer in women (4.3%) [1].

According to the Hertsen Moscow Oncology Research Institute, in 2022, endometrial cancer ranked fourth among all cancers, accounting for 7.1% of the total number of MN cases [2].

Living in ecologically compromised territories can significantly increase the risk of diseases of the female reproductive system [3–9]. According to researchers [3], chronic exposure to heavy metals can lead to breast cancer, endometriosis, hypertension, menstrual disorders, and spontaneous abortions, as well as premature birth and stillbirth. It was established that metalloestrogen cadmium induces UBC, elevated lead levels have a teratogenic effect and can cause spontaneous abortion, and mercury affects the menstrual cycle and can lead to infertility [3]. According to [4], cadmium is a potential risk factor for hormone-dependent tumors, such as UBC, because the vascular endothelium is a target of cadmium toxicity, which can affect coagulation processes and the fibrinolytic system. Patients with fibroids and especially UBC were found to have disrupted coagulation and fibrinolysis, which translate into hypercoagulation [4]. A monitoring of 62,534 women who survived the atomic bombing (1958−2009) [5] revealed a significant relationship between the radiation dose and the risk of UBC, which indicates that the uterine corpus is particularly sensitive to the carcinogenic effect of radiation.

According to [10–12], the southwestern territories of the Bryansk Region remain highly contaminated with cesium-137 (¹³⁷Cs) from the Chernobyl accident. The contamination levels exceed those that classify the area as radioactively contaminated, and the average annual effective doses exceed 1 mSv per year, reaching maximum values of up to 5.6 mSv/year [13, 14].  In recent years, the Bryansk region has seen an increase in the release of gaseous pollutants into the atmosphere [15, 16]. It is important to note in some areas of the region the population is exposed to both radioactive and chemical contamination factors (combined exposure) [17–19]. A study [19] found that the relative risk (RR) of UBC among women aged 18–80 years living in ecologically compromised areas was significantly higher than in control regions. In addition, continued environmental pollution accelerates the mutation process, which increases the population load [20].

This study aimed to calculate the relative risk (RR) and the frequency of primary incidence of UBC among women aged 41-60 years living in areas with different levels of exposure to radiation, chemical, and combined environmental factors. The analysis considered high-, moderate-, and low-grade forms of UBC over a 20-year period (2000–2019).

METHODS

The post-Chernobyl radioactive contamination density data (¹³⁷Cs and ⁹⁰Sr) were taken from [12], the average annual effective dose data ― from [14], the data on the level of CO, NO_x, SO₂ and volatile organic compounds (VOCs) in the air ― from [15]. The study covered the years 2000–2019.

Based on official data from the Bryansk Regional Oncological Dispensary [21], we calculated the RR and the frequency of primary incidence of high-, moderate-, and low-grade forms of UBC, taking into account the levels of chemical and radioactive contamination. The study covered the period from 2000 to 2019. We performed a histological analysis of UBC samples collected from 1,030 women aged 41–60 years.

For statistical analysis, we used the Shapiro–Wilk test, the Mann–Whitney U test, and calculated 95% confidence intervals. Levels of statistical significance were set at p < 0.05, p < 0.01, and p < 0.001. The absolute values of the incidence of UBC were recalculated per 100,000 female population [15]. We used MyOffice package (New Cloud Technologies; Russia) for analysis of the data collected.

RESULTS

Based on the degrees of radioactive and chemical contamination and the level of primary incidence of UBC over a twenty-year period (2000−2019), we divided the Bryansk region into four groups. The results of this effort are given in tab. 1; the analysis of the data therefrom was part of an earlier work [19].

The incidence of high-, moderate-, and low-grade forms of UBC is 21.0%, 18.1% and 14.4% higher in women living in contaminated areas (combined, radioactive, and chemical contamination) compared to the female population of the control areas: 29.4 ± 4.8; 28.7 ± 5.1 and 27.8 ± 4.1 versus 24.3 ± 4.2 (tab. 2). However, no significant differences between the groups were found (p > 0.05). The frequency of high-grade forms of UBC is higher in women living in territories with radioactive (15.6 ±3.1) and combined (15.4 ± 3.2) contamination compared to those residing in chemically contaminated areas (13.1 ± 2.0) and control territories (10.6 ± 2.0). A similar trend was registered for low-grade forms of UBC: territories with radioactive contamination ― 3.6 ± 1.5, combined contamination ― 3.5 ± 1.0, chemically contaminated areas ― 3.1 ± 0.6, and control territories ― 2.7 ± 0.7. The incidence rate of moderately differentiated forms of UBC varies only slightly through cities and districts of the Bryansk region ― from 10.5 to 11.7. The environmental conditions have no effect thereon; the peak value of 11.7 is registered in the territories with chemical pollution (tab. 2). It should be noted that we did not observe significant differences between the groups, whether divided by the form of UBC or by the grade of the disease (tab. 2).

Based on the data from tab. 3, it can be concluded that women living in the environmentally compromised areas (including territories with chemical, radioactive, and combined contamination) have an increased incidence of high-, moderate- and low-grade forms of UBC compared with women living in environmentally safe (control) areas. The mean RR is 1.16 (95% CI: 0.98–1.36); its values are generally higher than those calculated for the control areas: in the chemically contaminated territories, the RR is 1.14 (95% CI: 0.97–1.35), in the areas of radioactive pollution — 1.18 (95% CI: 0.91–1.54), combined pollution — 1.21 (95% CI: 0.96–1.53). We did not register increased RR for primary incidence of UBC in comparison of the territories with different types of contamination: the values vary between 1.02 and 1.06.

An analysis of data from tab. 4 revealed a significant (p = 0.047) increase of the RR of incidence of UBC. The highest RR was registered for high-grade forms of the disease in women residing in ecologically compromised areas (chemical, radioactive, and combined contamination jointly). In the control areas, the RR was 1.28 (95% CI: 1.00–1.64). Compared to environmentally safe areas, the RR growth rates were 1.47 (95% CI: 1.01–2.13) for territories of radioactive contamination, 1.45 (95% CI: 1.04–2.03) in the combined contamination areas, and 1.23 (95% CI: 0.96–1.59) in the chemically contaminated territories. The form-wise comparison to the overall UBC incidence rate revealed an increased RR between the territories of radioactive and chemical contamination ― 1.19 (95% CI: 0.87–1.63), combined and chemical contamination ― 1.18 (95% CI: 0.90–1.55). However, there was no RR increase between the territories of combined and radioactive contamination ― 0.99 (95% CI: 0.67–1.46). In all likelihood, these data suggest that accident-related radiation plays a greater role in the formation of highly differentiated forms of UBC than chemical pollution. 

There was no increase in the primary incidence of moderate-grade (tab. 5) and low-grade (tab. 6) forms of UBC in women living in ecologically compromised areas compared with environmentally safe areas: the RR for  moderately differentiated forms was 1.06 (95% CI: 0.82–1.34), low-grade forms ― 1.03 (95% CI: 0.63–1.69). In addition, we registered no growth of RR for moderate-grade UBC between control territories and territories of chemical radioactive and combined contamination ― the values range from 0.97 to 1.07 (tab. 5). The rates of primary incidence of moderately differentiated forms of UBC between the areas of chemical, radioactive and combined contamination vary between 0.64 and 0.98, and there are significant differences (p = 0.019) between the chemically and radioactively contaminated areas: RR 0.64 (95% CI: 0.44–0.93). These data indicate a higher incidence of moderately differentiated forms of UBC in women living in areas of chemical contamination relative to areas of radioactive contamination. In contrast to the primary incidence of moderate-grade forms of UBC, we found an increased relative risk of low-grade forms thereof between control territories, territories of radioactive contamination (RR 1.30 (95% CI: 0.60–2.79)) and territories of combined exposure (RR 1.28 (95% CI: 0.64–2.54)) (tab. 6). However, between chemically contaminated areas and control territories the RR was not increased: 0.95 (95% CI: 0.57–1.59) (tab. 6).

As tab. 6 shows, there is an increased RR of low-grade forms of UBC between territories of radioactive and chemical contamination – 1.36 (95% CI: 0.70―2.65), and areas of combined and chemical contamination – 1.34 (95% CI: 0.75-2.39). There was no such increase registered between territories of combined and radioactive contamination ― RR 0.98 (95% CI: 0.44−2.21). The data for low-grade forms of UBC (tab. 6) are similar to the results for highly differentiated forms of UBC (tab. 5); they suggest that, in all likelihood, accident-related radiation plays a greater role in the formation of low-grade forms of UBC than chemical pollution. 

DISCUSSION

There are many risk factors affecting the occurrence of UBC, and it is virtually impossible to make provisions for them [22, 23].

A study [24] that investigated the dependence of the UBC incidence rate on anthropogenic impact found that before the age of 45, its role in the development of endometrial cancer is less significant than after 45.

In [25], it was found that the combined effects of radiation and chemical contamination increase the incidence of low-grade ovarian malignancies compared with areas affected by only one pollution factor. Consequently, the authors of that study concluded that radiation and chemical factors act synergistically. In this study, no such pattern was observed, but we established an increased RR of incidence of high- and, to a greater extent, low-grade forms of UBC between territories of radioactive and chemical contamination, combined and chemical contamination, although no increased RR was found between territories of combined and radioactive contamination. 

A limitation of this study was that it did not take into account the stage of the disease or its immunohistochemical profile.

CONCLUSIONS

1. The incidence of high-, moderate-, and low-grade forms of UBC is 21%, 18%, and 14% higher among women living in areas of combined, radioactive, and chemical contamination compared with control areas; however, there are no significant differences between the groups.
2. The relative risk (RR) of developing a high-grade form of UBC is higher among women residing in ecologically compromised territories (chemically, radioactively contaminated areas and areas with combined pollution factors) compared with those living in environmentally safe (control) territories: RR 1.28 (95% CI: 1.00–1.64); p = 0.047).
3. The RR of primary incidence of moderate- and low-grade forms of UBC among women living in ecologically compromised areas is comparable to that of women in control territories, with values ranging from 1.03 to 1.06.
4. Other findings include an increased relative risk (RR) of occurrence of both high- and, to a greater extent, low-grade forms of UBC in areas with high radioactive and chemical contamination — 1.19 (95% CI: 0.87–1.63) and 1.36 (95% CI: 0.70–2.65), respectively; the relative risks for combined and chemical contamination areas were 1.18 (95% CI: 0.90–1.55) and 1.34 (95% CI: 0.75–2.39), respectively; no increase was observed between the territories with combined and radioactive contamination — 0.99 (95% CI: 0.67–1.46) and 0.98 (95% CI: 0.44–2.21).
5. In all likelihood, the data from this study indicate that accident-related radiation contamination plays a more significant role in the development of high-grade — and especially low-grade — forms of UBC than does chemical contamination.