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and IL-6 and TNF-a (r = 0.65, p < 0.05). In women with AIT in the stage of overt hypothyroidism was observed a direct correlation between IL-10 and IL-6 (r = 0.82, p < 0.001), IL-10 and TNF-a (r = 0.91, p < 0.001) between IL-6 and TNF-a (r = 0.72, p < 0.001), IL-6 and ATPO (r= 0.51, p < 0.05) and an inverse correlation between TSH levels and fT4 (r = -0.51, p < 0.05). In euthyrosis stage there was a direct correlation between IL-1^ and IL-6 (r = 0.73, p < 0.001), IL-10 and TNF-a (r = 0.78, p < 0.001), IL-10 and ATG (r = 0.44, p < 0.05) between IL-6 and TNF-a (r = 0.54, p < 0.05) and IL-18 and TNF-a (r = 0.48, p < 0.05).
Thus, the study of the dynamics of the parameters of immune and hormonal status and the results of correlation analysis indicate a close relationship between hormonal disorders and immunological changes in patients with Hashimoto's thyroiditis and reproductive dysfunction.
Conclusions:
1. Identification of high levels of pro-inflammatory cytokines and dynamics, depending on the phase of the AIT confirms the role of immune disorders in the development and progression of thyroid dysfunction at AIT. The results of the analysis of correlation showed a directly proportional relationship between IL-1p, IL-6 and TNF-a in all patients with Hashimoto's thyroiditis, regardless of the functional state of the thyroid gland. There was a direct correlation between IL-1p and ATPO, IL-6 and ATPO underway thyrotoxicosis, between IL-6 and ATPO underway between overt hypothyroidism and IL-1p and ATG in phase euthyrosis. The data may serve as inputs in assessing the dynamics of the autoimmune process and the effectiveness of the therapy.
2.
3.
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9.
10.
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Geva E., Vardinon N., Lessing J. B., Lerner-Geva L., Azem F., Yovel I., Burke M., Yust I., Grunfeld R., Amit A. Organ-specific autoantibodies are possible markers for reproductive failure: a prospective study in an in-vitro fertilization-embryo transfer programme// Hum Reprod. - 1996, Aug. - 11(8): 1627-1631.
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Kim C. H., Chae H. D., Kang B. M., Chang Y. S. Influence of antithyroid antibodies in euthyroid women on in vitro fertilization-embryo transfer outcome//Am J Reprod Immunol. - 1998, Jul. - 40(1): 2-8.
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Khudaykulov Atabek Tillaevich, National Cancer Research Center, Tashkent, Uzbekistan, Doctoral candidate of the Republican cancer research center
E-mail: [email protected]
The impact of demographic change on the incidence of breast cancer in Uzbekistan
Abstract: In the cancer incidence breast cancer (BC) ranks first with a specific gravity of11.7 % among the female population in Uzbekistan. The areas of increased and reduced disease risk are identified. The incidence of breast cancer is associated with the peculiarities of medico-demographic situation in the regions. The incidence of breast cancer among the population is
The impact of demographic change on the incidence of breast cancer in Uzbekistan
significantly affected by the average age of the women (59.6 %) and the odds of divorce rates (27.4 %), less mo rtality (11.5 %) and fertility (-9.5 %).
Keywords: breast cancer, the medico-demographic situation of Uzbekistan.
Introduction
The incidence of breast cancer (BC) is increasing worldwide. According to IARC in 2012, the most common cancer was lung cancer (13 %), breast cancer (11.9 %), colorectal cancer (9.75 %). From 2007 to 2012 there has been a sharp increase in the incidence of breast cancer. In 2012, 1.7 million women were diagnosed with breast cancer. In comparison with data for 2008, the number of cases of breast cancer increased by 20 %, mortality increased by 14 %. Breast cancer is the most common cause of death among women with cancer (522 000 deaths in 2012) and the most frequently diagnosed cancer among women in 140 of 184 countries. Today, one in four women with cancer suffers from breast cancer [7, 1-3]. In the structure of cancer incidence breast cancer ranks first among the female population of Russia and the CIS States. It ranks from 18-22 % in Russia, Belarus, Kazakhstan and Kyrgyzstan to 25-33 % in Uzbekistan, Azerbaijan, and Armenia [3, 77-78]. The prevalence of malignant tumors of the mammary gland to some extent related to demographic characteristics of the population. The study analyzed the relationship between the predictors characterizing the demographic situation (birth rate, marriage rate, divorce rate, death rate, life expectancy, migration and the average age of women), and standardized performance (SP) in the incidence of malignant mammary tumors.
The purpose of the study is to study the impact of key demographic and health indicators on the incidence of breast cancer.
Materials and methods
The incidence of breast cancer has been studied on the territory of the Republic of Uzbekistan covering its 14 administrative regions, including the city of Tashkent. Source material for the study of epidemiological and statistical data on breast cancer were included into the cancer register of the National Cancer Center. Data on the numerical composition of the population in the regions, birth rate, marriage rate, divorce rates, mortality rates, life expectancy and migration were obtained [1, 70-71] and from official site of the State Committee of the Republic of Uzbekistan (www.stat.uz). The calculation of the intensive and standardized indicators was carried out according to methodical recommendations of the Moscow Research Oncology Institute n. a. P. A. Herzen [4, 116-123]. To determine the effects of demographic factors on the incidence of breast cancer we conducted a paired correlation analysis Karl Pearson and the formation of a linear regression model. To calculate the predictive incidence a linear regression equation was built. Found measure of relationship is expressed by the equation:
7 = a + b1X1 + b2X2 + b2X3 + ... + bXn, where Yis the dependent attribute; a is the constant, X1, ..., Xn — independent characteristics; b1, ..., bn — regression coefficients. To establish the level of difficulty of communication dependent symptom Y with the whole set of factor signs X, ..., Xn, we calculated the coefficients of multiple correlation (R). Because the multiple regression model was based for the sample population, significance of coefficient of multiple correlation R was monitored by means of F-criterion of Fisher [5, 213-221].
When interpreting probabilistic estimates of the outcomes of the observations we take into account that the truth of the result is not determined for a wide General population, and the degree of regularity doesn't regards to accidental actions [6, 17-52]. The
contribution of factor (X;) in the formation of the incidence rate (Y) was calculated by the formula:
K. ■ R2 -100%,
' IA '
where K. — is the contribution of the corresponding factor (X), R 2 — determination coefficient, ft. is the standardized coefficient Beta of the corresponding factor (X). Statistical analyses were carried out using the programs Excel 2003, Statistics 6.0.
Results and discussion
Breast cancer is one of the main localizations of malignant tumors among women of the Republic. From 2001 to 2010 a total of18 671 breast cancer cases was registered. The absolute number of cases in 2010 to 1.51 times more than in 2001, the proportion of breast cancer in the structure of oncologic morbidity of female population has increased from 7.0 to 11.75 %. High this indicator is high in Tashkent (15.0 %), Tashkent region (14.0 %) (in the Republic of Uzbekistan, 2010 — 11.75 %). The most negative effects of breast cancer was relevant for women young and middle age. At the age of 44 years, the share of the disease in the structure of oncologic pathology in women is 24.5 %, 45-64 is 26.8 %, 65 years and older is 13.7 %, i. e. practically every fourth malignant tumor found in women young and middle age [7, 95-97]. One of the main indicators characterizing demographic situation in the study area is the birth rate, which is the positive process of reproduction of the population. Complex factors such as socioeconomic circumstance in the country, the situation of women in society, the level of medical care to mothers and children, national and religious traditions, etc. affect its value. Analysis of correlations between incidence of breast cancer female population of administrative territories of the Republic for 2010 and demographic predictors revealed the presence of a negative relationship between morbidity and fertility rate (R = -0.90; p = 0.05). Higher fertility was observed in areas with a high proportion of indigenous inhabitants (tab. 1).
The birth rate in Jizzakh (of 23.2 %), Kashkadarya (from 24.4 %), Samarkand (to 24.1 %), Surkhandarya (24.6 %) and Khorezm (23.0 %) regions during the period analyzed was slightly higher than the national average (22.6 %). Low birth rates are typical for urbanized areas: Tashkent (21.20 %) and Navoi (21.6 %) regions, with a high proportion of the urban population (at 39.6 % and 39.9 %, respectively; the national average of 36.4 %) and expressed as factor of migration (migration outflow of 10.6 % and 16.1 %, respectively; the national average 6.56 %). An important cause of birth control — the instability of conjugal relations. The higher the divorce rate, the lower the number of births. The direct correlation between morbidity and the number of divorces, the greater the number of divorces in the population (R = 0.87; p = 0.05), the higher the incidence rate (Fig. 1).
Higher incidence is observed in areas with relatively high rates of divorce rates per 1000 population — in the city of Tashkent (1.56 %) and Tashkent (0.85 %), and Syrdarya (of 0.83 %). Minimal values are typical for areas, where there are mainly inhabitants of the indigenous nationality: Surkhandarya (to 0.24 %) and Kashkadarya (0.3 %).
Determining the reproductive behavior of the population, marriages and divorces affect fertility. Divorce leads to a reduction of the reproductive period of women. Mortality rates and life expectancy
of the population are the main criteria characterizing the demographic situation. As you know, social and environmental factors have a complex impact on the nature and trends of mortality. The mortality was significantly influenced by lifestyle, working conditions, social infrastructure, etc. Higher incidence of breast cancer
Table 1. - Demographic characteristics
observed in areas with relatively high rates of General mortality of the population in Tashkent city (7.2 %) and Tashkent (5.9 %), Andijan (5.0 %) and Syrdarya (5.2 %) regions. Found a direct linear correlation between SP the incidence of breast cancer and the coefficient of total mortality (Fig. 2). of the regions of the Republic (2010)
Region The standardized incidence rate per 100,000 population Mean age The rate per 1,000 of the population
Fertility The divorce rate Mortality
The Republic of Karakalpakstan 8.5 27.2 23.24 0.55 5.11
Andijan 11.2 28.2 23.51 0.54 5.04
Bukhara 11.1 28.8 21.45 0.55 4.57
Jizzakh 11 27 23.22 0.44 3.97
Kashkadarya 8.3 26.4 24.41 0.30 3.92
Navoi 10.8 28.6 21.61 0.58 4.67
Namangan 6.6 27.6 22.49 0.75 4.67
Samarkand 8.6 27.1 24.11 0.60 4.57
Surkhandarya 6.5 26.2 24.62 0.24 4.07
Syrdarya 10.6 26.6 22.76 0.83 4.82
Tashkent 14.3 29.6 21.20 0.85 5.94
Fergana 10 28.3 22.96 0.48 5.16
Khorezm 9.3 27.2 23.03 0.57 4.49
Tashkent city 26 33.5 17.59 1.56 7.22
Across the republic 10.9 28.0 22.67 0.63 4.94
Fig. 1. The standardized incidence of breast cancer, fertility rates, mortality rates, divorce rates and the average age of women in the areas of the Republic
The higher mortality rates in the population (R = 0.87; p = 0.05), the greater the incidence. This is because in areas with high mortality partly women die from breast cancer.
As it is known, age is an important risk factor. The likelihood of developing breast cancer increases in proportion to age. Malignant breast tumors most often affect people older than 60 years. The disease often develops in pre-menopausal and menopausal age [2, 64-73]. The direct correlation between the incidence of breast cancer and middle-aged women, the older the average age of women in the population (R = 0.93; p = 0.05), the higher the incidence rate. The highest morbidity is observed in
areas with relatively high average ages of women in Tashkent city (33.5 years) and Tashkent (29.6 years), Navoi (28.6 years), Bukhara (28.8 years) and Andijan (28.2 years). The minimum value of SP morbidity typical for areas, where women live with a relatively young average age: Surkhandarya (26.2 years), and Kashkadarya (26.4 years). Except in fertility rates, divorce rates, mortality and middle-aged women were analyzed correlations between standardized incidence rates of breast cancer and the marriage rate (r = -0.31), life expectancy (r = -0.31), natural population growth (r = -0.36), migration inflow (r = 0.39) and outflow (r = 0.28) of the population.
Clinical biochemical features in patients with undifferentiated connective tissue dysplasia
24,1144598 21,2034495
17,5956675
• •
-----
~ o—^^^ Fertility ""-o^The divorse rate Mortality \| Mean age
•___ •
1 ! 1 ! _______;
=-5- —lP c □ Tjp- n ! !
10
12
14
16
18 20
22 24 26 28
Fig. 2. The correlation between the standardized incidence rate of breast cancer and divorce rates, fertility, mortality and middle-aged women
Although between these factors and SP were found in the incidence of correlation, they were not significant (p > 0.05). Therefore, these factors are not included in the linear regression model. To define measures of the identified relationships was regression analysis. The following multiple linear regression equation:
7 = -62.7 + 6.05*X1 + 2.25 *X2 + 0.46 *X3 - 0.78 *X4; R = 0.94, R 2 = 0.89, F = 18.1; p < 0.00025, where: Y — the incidence rate of breast cancer,
X1 — the divorce rates; X2 — the average age of women; X3 — fertility rate, X4 — coefficient of total mortality; R — coefficient of multiple correlation; R 2 — coefficient of determination, F — Fisher's criterion.
On the incidence ofbreast cancer in the population is strongly influenced by the average age of the women (59.6 %) and the odds of divorce rates (27.4 %), less mortality (11.5 %) and fertility (-9.5 %).
In conclusion it should be said that in areas where there is a low birthrate, high divorce rates, total mortality and the high average age of women we can expect an increased incidence of breast cancer. The average age, reproductive behavior of women, the divorce rate and overall mortality of the population, causing the state of the demographic situation in the territories and played a leading role in the incidence of breast cancer. The organizers of health in the development of preventive measures is necessary to consider the medico-demographic situation of the region.
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Uzbekistan Almanac 2013. - Tashkent, 2015.
Bershtein L. M. Hormonal carcinogenesis/L. M. Bershtein. - SPb., 2000. - 272 p.
Davydov M. I., Axel E. M. Statistics of malignant neoplasms in Russia and CIS in 2012. - Moscow, 2014.
Organization of oncological service in Russia (methodical recommendations, manuals for physicians). Part 2. Edited by V. I. Chissov, V. V. Starinsky, B. N. Kovalev. - Moscow, 2007. - 663 p.
Rebrova O. Y. Statistical analysis of medical data. The use of the STATISTICA software package. - M.: Mass Media, 2002. - 312 p. Tikhomirov N. P., Dorokhina E.J. Econometrics: A Textbook. - M.: Ekzamen, 2003. - 512 p.
Khudaykulov T. K., Khudaykulov A. T. Epidemiological aspects of breast cancer in Uzbekistan//Bulletin of the Tashkent medical Academy. - 2013. - No. 3. - P. 95-97. Lyon Geneva, 12 December 2013.pdf.
Shodikulova Gulandom Zikriyaevna, Samarkand State Medical Institute, Uzbekistan Toirov Erkin Sanatovich,
Babamuradova Zarrina Bahtiyarovna E-mail: [email protected]
Clinical biochemical features in patients with undifferentiated connective tissue dysplasia
Abstract: The research objective is represented by the implementation of comparative performance analysis of NO-system, VEGF, expression indices of MMP-2, MMP-9, TIMP and magnesium level, GAG, HN in the blood of patients with congenital
