Acording to recent WHO GLOBOCAN 2020 estimates [1], the increase in the global rate of malignant neoplasms (MNs) to 19.3 million incident cases and 10.0 deaths is reported. Malignant neoplasms of the ovaries (MNOs) occupy the seventh place among all cancer types being generally one of fatal diseases affecting female reproductive system [2]. According to the data provided by the Blokhin National Medical Research Center of Oncology, MNOs are second only to endometrial cancer and cervical cancer based on the incidence rate in Russia [3].

The papers [4–12] report a significant correlation between the risk of MNOs and the increase in environmental ill-being. 

Radioecological monitoring of the South-Western areas of the Bryansk Region suggests that the cesium-137 (¹³⁷Cs) contamination density exceeds the established radiological standards 37 years after the Chernobyl accident, and the average annual effective doses reach hundreds  mSv [13–18]. Furthermore, an increase in the emission of pollutants into the atmosphere is reported for the Bryansk Region in recent years [19].

In certain areas of the Bryansk Region, the population is exposed to combined effects of radioactive and chemical contamination [20–22].

Thus, environmental pollution results in the mutation rate increase, which creates a threat to the genetic security of all living things [23].

The study aimed to perform comparative assessment of environmental situation in the towns and districts of the Bryansk Region based on chemical, radioactive, and combined radioactive contamination, as well as primary incidence of MNOs in women in accordance with official statistics for the years 2000–2019.

METHODS

The analysis of density of the cesium-137 (¹³⁷Cs) and strontium-90 (⁹⁰Sr) contamination resulting from the Chernobyl accident was conducted based on the data [17], the average cumulative effective doses (CED₉₀) were assessed based on the data [24], the levels of the atmospheric air chemical pollution with CO, NO_x, SO_2, and volatile organic compounds (VOCs) were assessed based on the data [25] for the years 2010–2019.

The incidence of newly diagnosed MNOs in female population (aged 18–80 years) of the Bryansk Region was analyzed using the official data provided by the Bryansk Regional Oncology Dispensary [26]. A total of 2647 MNO cases were revealed in 2000–2019. The analysis of the MNO histological forms was performed in the reported 942 cases (age 41–60 years). Absolute values were recalculated per 100,000 population.

Linear regression and relative risk (RR) of primary MNO incidence were calculated depending on chemical and radioactive contamination levels for the period of 2000–2019. Statistical analysis was performed using the Shapiro–Wilk test, Mann–Whitney U test, Spearman’s rank correlation, linear regression; 95% confidence intervals (95% CI) were calculated; the significance levels were as follows: р < 0.05, p < 0.01, p < 0.001. Statistical analysis of the data obtained was performed using the MyOffice software package (New Cloud Technologies; Russia).

RESULTS

Towns and districts of the Bryansk Region were divided into four groups based on chemical and radioactive contamination levels, as well as primary incidence of MNOs in 2000–2019 (tab. 1). Analysis of the results provided in the table was earlier reported in the paper [27].

Analysis of the data provided in tab. 2 showed that there was no increase in the RR of MNOs among women in the territories with chemical, radioactive, and combined contamination compared to the control (environmentally safe) territories: RR 1.07 (95% CI: 0.96–1.19). However, the risk of MNOs in women living in the chemically contaminated territories was slightly higher, than in women living in the control districts (RR 1.11 (95% CI: 1.00–1.23)), but the differences were non-significant (р = 0.06). It should be noted that we revealed a significantly (р = 0.005) increased risk of MNOs in the chemically contaminated territories relative to the radioactively contaminated areas: RR 1.26 (95% CI: 1.07–1.48). No such patterns were revealed in other territories (tab. 2). 

As shown in figure, a significant increase in the long-term trend of primary MNO incidence was revealed in the group of chemically contaminated territories only (p < 0.05).

Comparative assessment of primary incidence of high-grade, intermediate grade, and low-grade MNOs among women aged 41–60 years living in environmentally different territories of the Bryansk Region in 2000–2019 showed that the rate of high-grade MNOs in the environmentally safe territories was 7.1 ± 0.83, which exceeded the values of the territories with radioactive (1.4 ± 0.65), chemical (1.6 ± 0.35), and combined (3.2 ± 0.75) contamination 5.1-fold, 4.4-fold, and 2.2-fold, respectively (р < 0.001) (tab. 3).   

We revealed no significant differences in the rate of intermediate grade MNOs in the towns and districts of the Bryansk Region, regardless of the living conditions (the values vary between 7.0 and 8.8) (tab. 3). 

The rate of low-grade MNOs in the chemically contaminated territories is 15.2 ± 1.31, which 1.3-fold (р < 0.05) exceeded the values of the radioactively ccontaminated territories (11.7 ± 2.73), suggesting the leading role of chemical factor vs. radioactive in shaping the incidence of MNOs (tab. 3).  

The rate of low-grade MNOs in the areas with combined contamination reaches its maximum (17.6 ± 1.96), it 2.2-fold exceeds (р < 0.001) the values of the control areas (8.1 ± 1.20), 1.5-fold (р < 0.05) the values of the radioactively contaminated areas (11.7±2.73), and 1.17-fold (р > 0.05) the values of the chemically contaminated areas (15.2 ± 1.31). The results obtained suggest synergistic effect of radiation and chemical factors on the incidence of low-grade MNOs (tab. 3). 

Analysis of the data provided in tab. 4 revealed a significant increase in the RR of primary incidence of low-grade MNOs in women aged 41–60 years living in the environmentally disadvantaged areas (territories with chemical, radioactive, and combined contamination in total) relative to the environmentally safe (control) territories (RR 1.88 (95% CI: 1.43–2.48); p < 0.0001). Furthermore, RR was significantly increased in the territories with radioactive (RR 1.45 (95% CI: 0.95–2.23)), chemical (RR 1.88 (95% CI: 1.42–2.50)), and to the greater extent combined contamination (RR 2.20 (95% CI: 1.55–3.11)) of the environment compared to the control areas.

The combined effects of radioactive and chemical contamination resulted in the higher RR of low-grade MNOs compared to the territories with only one pollution factor, i.e. radioactive contamination (RR 1.51 (95% CI: 1.00–2.28)), chemical contamination (RR 1.17 (95% CI: 0.90–1.50)) (tab. 4).  The findings have been fully confirmed by analysis of the data provided in tab. 3.

DISCUSSION

The papers [28, 29] report that the incidence of solid low-grade MNOs became higher compared to the incidence of high-grade MNOs with increasing levels of chemical [28] and radioactive [29] environmental contamination, which suggests worse outcomes characterized by low 5-year survival and early metastasis. 

The findings confirm the research data [28, 29] and suggest the increase in the rate of low-grade MNOs in women aged 41–60 years living in the environmentally disadvantaged territories, with the most significant increase under combined exposure to radiation and chemical factors.

It should be noted that the fact that the analysis of MNO incidence in female population did not consider the distribution by disease stages and immunohistochemistry profiles was a limitation of the study.

CONCLUSIONS

1. The study revealed neither significant differences in primary incidence of malignant neoplasms of the ovaries (MNOs), nor increased risk of MNOs in the female population aged 18–80 years, regardless of environmental conditions of living in 2000–2019.
2. We determined a significant increase in the relative risk (RR) of primary incidence of low-grade MNOs in women aged 41–60 years living in the environmentally disadvantaged areas (territories with chemical, radioactive, and combined contamination in total) relative to the environmentally safe (control) territories (RR 1.88 (95% CI: 1.43–2.48); p < 0.0001).
3. It was shown that the rate of low-grade MNOs in women aged 41–60 years in the territories with the combined exposure was 17.6 ± 1.96, which 1.5-fold exceeded the values of the radioactively contaminated territories (11.7 ± 2.73) and 1.2-fold exceeded the values of the chemically contaminated territories (15,2 ± 1,31).
4. The combined effects of radioactive and chemical contamination resulted in the higher RR of the incidence of low-grade MNOs compared to the territories with only one pollution factor, i.e. radioactive contamination (RR 1.51 (95% CI: 1.00–2.28)), chemical contamination (RR 1.17 (95% CI: 0.90–1.50)).
5. The findings suggest synergistic effect of radiation and chemical factors on the incidence of low-grade MNOs.