Institute of Public Health of Serbia Dr Milan Jovanovic Batut. Attributable Causes of Cancer in Serbia in the Year 2005

Transcription

1 Institute of Public Health of Serbia Dr Milan Jovanovic Batut Attributable Causes of Cancer in Serbia in the Year 2005 Belgrade, 2008

2 Director of Institute of Public Health of Serbia Dr Milan Jovanovic Batut Tanja Knezevic, MD, PhD Department for Prevention and Control of Noncommunicable Diseases Dragan Miljus, MD, M. Sc., epidemiologist Snezana Zivkovic, MD, epidemiologist Snezana Plavsic, MD, epidemiologist Jelena Jankovic, MD, Sanja Savkovic, statistics engineer Consultants Prof. dr Hristina Vlajinac, MD, PhD, Academy of medical sciences Srpskog lekarskog društva Prof. Sandra Sipetic Grujicic, MD, PhD, Institute of epidemiology, Faculty of medecine, Belgrade Prof. Jelena Marinković, MD, PhD, Institute of medical statistics and informatics, Faculty of medecine, Belgrade Prof. Marica Miladinov Mikov, MD, PhD, Oncology Institute of Vojvodina, Sremska Kamenica, Faculty of medecine, Novi Sad Lidija Stankovic, dipl. engineer of information systems Neda Stojanovic, dipl. mathematics Sonja Mitov Scekic, dipl. mathematics Reviewers Prof. dr Hristina Vlajinac, MD, PhD Prof. Sandra Sipetic Grujicic, MD, PhD Translator Vesna Kostic 2

3 Table of contents 1. Background Objectives Methodology Incidence data Mortality data Population data Classifications of diseases, causes of diseases and death Cancer risk factors in Serbia Prevalence and exposure in Serbia Calculation of the attributable fraction Sensitivity analysis Cancer incidence and mortality in Serbia Discussion Cancer incidence and mortality rates in Serbia, Burden of leading risk factors in Serbia Selected cancer risk factors in Serbia Tobacco smoking Alcohol drinking Overweight and obesity Physical inactivity Chronic infections Use of oral contraceptives UV radiation Results Discussion

4 Background Malignant tumors are a group composed of numerous diseases of various localizations, morphology, clinical presentations and prognosis. Nowadays, these diseases are among the leading causes of morbidity, absenteeism and disability as well as early death worldwide. Malignant tumors have multifactorial etiology and result from complex interaction between individuals and environment they live in. Many risk factors associated with the occurrence of cancer may be linked to the lifestyle, environmental conditions or inheritance. Individual, socioeconomic and environmental features define the differences in exposure and susceptibility of individual for the occurrence of cancer. The lifestyle and environmental conditions that may lead to the occurrence of cancer are frequently subject to debate, particularly those relating to environmental factors are frequently differently interpreted. The number of risk factors linked with cancer increases over time, and it is believed that quite a number of them are yet to be discovered. Leading risk factors for the occurrence of cancer include smoking, obesity (irregular diet and physical inactivity), infections, reproductive and sexual behavior, occupation, alcohol drinking and environmental factors (ionizing and non-ionizing radiation, air pollution). It is estimated that only 2 to 4% of all cancer localizations may be associated with genetic defects. The role of numerous risk factors in carcinogenesis is only inferred, but not yet evidenced. Most of the aforementioned risk factors can frequently be associated with at least two locations of malignancies, and not rarely with more other chronic diseased. In many individuals, these risk factors are clustered, and their interaction frequently results in multiplication effect. The current level of knowledge makes it possible to prevent the occurrence of many malignant tumors. When resources and support are available, at least one third of malignant tumors could be diagnosed early and treated successfully. The report provides an evaluation of newly diagnosed cancer cases and cancer deaths that could be attributed to non-genetic risk factors. In 2005 cardiovascular diseases and malignant tumors accounted for over three quarters of all causes of death in Serbia. Over a half of fatal outcomes in Serbia (56.8%) resulted from diseases of the heart and blood vessels, and almost one in five deaths (18.5%) resulted from a malignant tumor; 3.6%, 2.7%, and 2.4% of the Serbian population died of injuries & poisoning, chronic respiratory diseases, and complications of diabetes, respectively. In comparison with 1985, the greatest rise in this mortality structure in 2005 was noted for malignant tumors (3.8%). 4

5 2. Objectives The purpose of the report is to assess the number of cancer cases and cancer deaths in Serbia that may be attributable to factors of demonstrated carcinogenicity. 3. Methodology Assessments of attributable risk factors are presented as proportions of specific cancer localizations in Serbia (2005) that could be attributed to selected, specific risk factors. The proportion of cancer in the population of Serbia that could be attributed to a risk factor is called the attributable fraction and is expressed as a percentage. The most straightforward method of attributable fraction (AF) assessment for the risk factors that could, at least theoretically, be avoided or completely eliminated, is to calculate the fraction of all cancer cases (exposed and unexposed to a certain factor) that would have not occurred if exposure had not occurred. In AF assessment for this report, it is assumed that unexposure does not imply total absence, but the presence of minimum levels of exposure to carcinogens instead. 3.1 Incidence data Although the national population cancer register in Serbia was established as early as 1970, the incidence data on malignant tumors in our country have been provided only recently. There are two population cancer registers in Serbia: one for central Serbia and the other for Vojvodina. In 2005 there was no central nationwide cancer register. The data on new cancer cases for the year were provided from the published data of the Central Serbia Cancer Register and unpublished (preliminary) data of the Vojvodina cancer register. Based on the two population registers, this report presents the assessed number of new cancer cases in Serbia in In addition to the total number of new cancer cases, we also presented the most common malignancies in men and women and their crude incidence rates. The report also presents not only the nonstandardized, but also standardized incidence rates. The stated rates were standardized using the direct standardization methods, and the population of Europe was used as the standard. 5

6 3.2 Mortality data We used the unpublished data of the on cancer mortality in Serbia for the period The specified data were analyzed at the Institute of Public Health by the standard five-year age intervals, sex and cancer localizations. In addition to non-standardized ones, mortality rates standardized for the population of Europe are also presented. 3.3 Population data Population estimates for the period were used as sources of population data by the five-year age intervals and sex in Serbia, except for 1991 and 2002 when the data were obtained from the respective censuses. The data were taken over from the National Statistics Bureau. The Republic of Serbia is composed of three administrative units: Central Serbia and two autonomous provinces (Vojvodina and Kosovo). Since the data for Kosovo have not been available ever since 1997, the presented data in this study relate to the territory of Serbia without Kosovo. 3.4 Classifications of diseases, causes of diseases and death Malignant tumors were coded pursuant to 10 th Revision of International Classification of Diseases (ICD-10), volume 1- (codes C00-C96) and International Classification of Diseases for Oncology - Third Edition (ICDO-3) (codes 8000/3-9941/3) -. World Health Organization Geneva. In situ tumors are not covered by this report (codes D00-D09). In the period 1985 to 1996 in Serbia malignant tumors were coded pursuant to 9 th Revision of International Classification of Diseases (ICD-9), volume 1- (codes ). In the stated period, colorectal cancer (ICD-9: codes ), included the codes of anal cancer (ICD-9: codes ). Since cancer codes could not be analyzed by the four-digit code, the anus code was added to the colorectal cancer code. Lung cancer (ICD-9: code 162) included tracheal cancer (ICD-9: code 162.0). Due to the reason stated above, the code of the tracheal cancer was added to the lung cancer code. Presentation of data on colorectal cancer and lung cancer coded by ICD-10 uses the same principle. Colorectal cancer (ICD-10: codes C18-C21), in addition to colon cancer and rectum cancer (ICD-10: codes C18-20), included anus cancer (ICD-10: code C21), as well; similarly, lung cancer (ICD-10: code C34) included tracheal cancer (ICD-10: code C33). 6

7 Malignant localizations of new cases of colorectal cancer and lung cancer were presented using the same principle. 3.5 Cancer risk factors in Serbia From the pool of risk factors, this report focused primarily tobacco, alcohol, oral contraceptives, chronic infections and UV radiation that are classified as group 1 of agents causatively associated with cancer, pursuant to IARC ( These factors were compounded by overweight and obesity as well as physical inactivity since there is a sufficient body of evidence to show that maintenance of normal body weight (avoidance of overweight and obesity) and physical activity have preventive effect on some malignant tumors. 3.6 Prevalence and exposure in Serbia In 2005 in Serbia cancer morbidity and mortality resulted from past exposure of the population to risk factors. For most of malignant tumors, the latency between initial exposure and occurrence of cancer is 15 years, meaning that exposure to risk factors in 1990 should be considered. Unfortunately, there are no available data on the prevalence of the selected risk factors in In early nineties and in the course of the decade Serbia experienced a turbulent period of country disintegration, war and migrations. So far, two (in 2000 and 2006) representative estimates of risk factor prevalence were made, based on standard methodology employed by the World Health organization (WHO). For evaluation of prevalence of exposure to risk factors in 1990 we used the model of linear interpolation and available data of exposure to risk factors from 2000 and 2006 health surveys. 7

8 3.7 Calculation of the attributable fraction Attributive fraction (AF) was calculated pursuant to Levin s method: AF= P(RR-1)/ [P(RR-1)] +1, where RR is the elative risk for the occurrence of cancer resulting from exposure to a risk factor, and P is the prevalence of the given factor in the population. The relative risk for certain malignant tumors associated with exposure to tobacco, oral contraceptives, chronic infections, UV radiation, overweight and obesity and physical inactivity have been taken over from the already cited IARC where the RR estimate was based on the data provided by meta-analysis comprising most representative studies. For continuous variables, such as alcohol drinking, the relative risk was calculated pursuant to the following formula: RR = Exp [(Ln (risk per unit)*average level of exposure)]. The cancer risk per unit of exposure represents the increase of cancer risk per unit of increased exposure and has been taken over from the already cited IARC. The average level of exposure in grams of alcohol per day was estimated for the population of Serbia on the basis of data obtained from the National Statistics Bureau on consumption of food and beverages. Since it is assumed that each individual experiences similar average exposure, we used a simplified Levi s formula for direct AF calculation: AF = Risk - 1 / Risk 3.8 Sensitivity analysis Different duration of the latent period between the first exposure and diagnosis of cancer, as well as years for which the data on the risk factor prevalence were available greatly determine the AF sensitivity analysis. When total absence of exposure was not present for a risk factor, sensitivity analysis was conducted by alternative approaches to exposure. 8

9 References E. Giovannucci. G. A. Colditz. S. Hankinson acancer Causes & Control. An International Journal of Studies of Cancer in Human Populations. Harvard University. Boston. MA. USA IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42. Supplement 7. Lyon Armitage P. Berry G. Statist cal Methods in Medical Research. second ed.. London. Blackwell Scientific Publications Attributable Causes of Cancer in France in the Year WHO. IARC Ken-ichi Kamo, Satoshi Kaneko, Kenichi Satoh, Hirokazu Yanagihara, Shoichi Mizuno, and Tomotaka Sobue. A Mathematical Estimation of True Cancer Incidence Using Data from Population-based Cancer Registries. Jpn J Clin Oncol 2007;37(2)

10 4. Cancer incidence and mortality in Serbia Data on the cancer incidence have been taken from the Central Serbia Cancer Registry, which is available for only. The cancer mortality data is taken from the National Statistics Office, relating to The incidence and mortality rates are calculated per 100,000 population and age-standardized to the population of Europe. Figures 1-3 present the standard incidence rates for all malignant tumor and most common malignant tumors in men and women in Central Serbia. In comparison with 1999 the incidence of all cancer localizations in Central Serbia (Figure 1) rose by 21.8% (from 321.3/100,000 to 391.5/100,000) in men and by 16.8% (from 276.3/100,000 to 322.7/100,000) in women. Figure 1. Cancer incidence rates by sex. Central Serbia Standardized rates per Males Females Years Standardized rates per 100,000 (European standard population) Source: published data from Cancer Registry of Central Serbia. Institute of Public Health of Serbia In the studied period, men most often contracted cancer of the lungs, colon and rectum, prostate, urinary bladder, stomach and pancreas (Figure 2). From 1999 to 2005 a rising trend was noted for all leading tumor sites except for the gastric cancer in men. In comparison with 1999, in 2005 the standardized incidence rate was increased by 60.3% in prostate malignancies, by 36.6% for urinary bladder cancer, by 28.6% for colon and rectum cancer, and by 15.5% for lung cancer. 10

11 Figure 2. Most frequent cancers in males - incidence by sites, Central Serbia, ,0 Lung (C33-34) 80,0 Standardized rates per ,0 40,0 Prostate (C61) Colon-rectum (C18-21) Urinary bladder (C67) 20,0 Stomach (C16) 0, Years Standardized rates per 100,000 (European standard population) Source: published data from Cancer Registry of Central Serbia. Institute of Public Health of Serbia In women, the malignant process was most commonly localized on the breast, colon&rectum, uterine cervix, lungs, uterus and stomach (Figure 3). With some variations in the incidence values, in a rise was noted in incidence rates for all leading sites of malignancy, except for cervical cancer (Figure 3) where an incidence fall of 3.5% (from 31.3/100,000 to 30.2/100,000) was recorded. The incidence rates are increased by 24.6% for colon&rectum malignancies, by 23.7% for lung cancer, by 17.1% for uterus and by 6.8% for breasts. Figures 4-5 illustrate standardized mortality rates for all malignancies and most common malignancies in male and female population of Serbia. In 1985 to 2005 rise of pooled mortality of all malignant tumors (Figure 4) by 34.5% (188.5/100,000 to 253.6/100,000) was recorded in males, and by 28.0% (124.3/100,000 to 159.1/100,000) in females. Most common causes of death in both males and females were the same malignancies that were the most common causes of morbidity. 11

12 Figure 3. Most frequent cancers in females - incidence by sites, Central Serbia, Breast (C50) 75 Standardized rates per Cervix (C50) Colon-rectum (C18-21) 25 Lung (C33-34) Corpus uteri (C54) Years Standardized rates per 100,000 (European standard population) Source: published data from Cancer Registry of Central Serbia. Institute of Public Health of Serbia Figure 4. Cancer mortality rates by sex, Republic of Serbia Standardized rate per Males Females Years Standardized rates per 100,000 (European standard population) Source: unpublished data from Serbian National Statistics Office 12

13 In the twenty-year period ( ) increased mortality of all leading malignancies in males (Figure 5) except for the stomach cancer was recorded. Standardized stomach cancer mortality rates fell by 5.0% (from 19.2/100,000 to 16.7/100,000). In the same period, however, the mortality rates related to colon&rectum malignancies rose by 69.4%, prostate by 52.6%, lung cancer by 50.4%and pancreas by 35.2%. Figure 5. Most frequent cancer mortality by sites, males, Republic of Serbia, Lung (C33-34) 80 Standardized rates per Prostate (C61) Colon-rectum (C18-21) 20 0 Stomach (C16) Pancreas (C25) Years Standardized rates per 100,000 (European standard population) Source: unpublished data from Serbian National Statistics Office In the same period, the rise of mortality rates of all leading cancer sites (Figure 6), except for the stomach cancer that is associated with a fall of mortality rate by 22.9% (from 10.5/100,000 to 8.1/100,000). Over the studied period, the mortality rates associated with lung cancer rose by 77.8%, breast cancer by 52.3%, colon&rectum cancer by 46.8% and cervical cancer by 23.8%. 13

14 Figure 6. Most frequent cancer mortality by sites, females, Republic of Serbia, Breast (C50) 30 Standardized rates per Colon-rectum (C18-21) Lung (C33-34) Cervix (C53) Stomach (C16) Years Standardized rates per 100,000 (European standard population) Source: unpublished data from Serbian National Statistics Office 4.1 Discussion Doll and Peto systematized the reasons that may lead the changes in cancer incidence and mortality. They suggest changes in classifications of diseases (histological and other), completeness of registration, population, diagnosis, early detection and screening, exposure to risk factors or protective factors that may be related to the cancer incidence and effectiveness of treatment.. The period for which we have the data on the incidence of malignancies in Central Serbia is too short to provide grounds for any trend-wise conclusions. It is, nevertheless, a fact that the incidence changes follow the mortality trend in the 20-year period. Rises of incidence of all malignancies (pooled data) and all leading sites, except for the stomach cancer could, probably, be attributed to better coverage and reporting of new cases of cancer. Since 2000, the reporting system for malignant tumors included persons covered by military health insurance (Military Medical Academy and military health centers) that significantly increased the registration coverage in Serbia. Continuous education of medical staff at the National Cancer Registry in Serbia over the same period has also contributed significantly to reporting of malignant tumors. 14

15 The rise of mortality may also be explained by improved diagnostics and reduced share of symptoms and unspecified conditions as causes of death, particularly in the initial part of the studied period, and also reduced success rate of treatment of malignancies during the economic sanctions in Serbia in the last decade of the twentieth century. However, lack of educational programs for primary and secondary preventions is the most probable cause of the increased cancer- associated mortality and morbidity in Serbia. In 1986 the EU members states launched a joint program entitled Europe Against Cancer in order to reduce the cancer mortality in the region by 15% by Owing to campaigns conducted in these countries, primarily anti-smoking ones, screening (cervix, breast and colonrectum) and activities on health promotion, the cancer mortality was reduced by 9% on the average (10% and 8%, in men and women, respectively). In Serbia, most of these activities are not in place. Serbia joined the anti-smoking campaign only recently, and the prevalence of smokers, particularly among men, is among the highest in Europe. According to the data obtained from a population health research conducted by the Public Health Institute in 2000, nutrition of the Serbian population is rich in fat and sugar, with little fresh fruit and vegetables, with consequent high percentage of obese and physically inactive people. Screening programs for cancer of the cervix, breast and colon are only in the preparatory stage or just launched (for cervical cancer). Insufficient awareness of the population on the importance of early treatment is another factor that contributes to poor prognosis of these diseases Fall of incidence and mortality associated with stomach cancer for both sexes in Serbia was noted in most European countries, as well. The reasons for decreased incidence and mortality rates associated with this cancer site are most probably linked with widespread use of antibiotics active against Helicobacter pylori, and food preservation by freezing instead of the use of salt and smoke. We have also investigated the possibility of the influence of population factors on the cancer mortality in Serbia in the last two decades and come to the conclusion that the changes in the population structure could not significantly influence the cancer mortality rate rise in the period Cancer incidence and mortality rates in Serbia, 2005 Table 1 illustrates the cancer incidence and mortality rates in Serbia in The 2005 cancer incidence rates were provided by unpublished preliminary data of the Vojvodina Cancer Registry and published data of the Central Serbia Cancer Registry. The data presented in the Table represent estimated incidence for the whole territory of Serbia. 15

16 Unpublished cancer mortality data have been taken over from the National Statistics Office and processed at the Public Health Institute. In addition to the overall cancer incidence and mortality rates in Serbia, selected localizations are also presented with their pertinent incidence and mortality rates. Table 1. Cancer incidence of and mortality rates in Serbia, 2005 Cancer site ICD 10 Incidence* Mortality** Males Females Males Females Number of cases Crude rate Number of cases Crude rate Number of deaths Crude rate Number of deaths Crude rate Oral cavity C Pharynx C Esophagus C Stomach C Colon-rectum C Liver C Pancreas C Larynx C Lung C Melanoma C Non-melanoma skin cancer C Breast C Cervix uteri C Corpus uteri C Ovary C Prostate C Kidney C Urinary bladder C Central nervous system C Hodgkin disease C Non-Hodgkin lymphoma C C Leukemia C Other All cancers Crude rate per person years * estimates: - sources: 1. preliminary data from Cancer Registry of Vojvodina, Oncology Institute of Vojvodina. (Author: Prof. Marica Miladinov-Mikov. MD.Ph.D) and 2. published data from Cancer Registry of Central Serbia, Institute of Public Health of Serbia **Source: unpublished data from Serbian National Statistics Office 16

17 References Doll R. Peto R. The Causes of Cancer. Appendix C. Oxford University Press pp Boyle P. d Onofrio A. Maisonneuve P. et al. Measuring progress against cancer in Europe: has the 15% decline targeted for 2000 come about? Annals Oncol 2003;14: Bray F. McCarron P. Parkin DM. The changing global patterns of female breast cancer incidence and mortality. Breast Cancer Res 2004;6: Ciccolallo L. Capocaccia R. Coleman MP. et al. Survival differences between European and US patients with colorectal cancer: role of stage at diagnosis and surgery. Gut 2005;54: Ferlay J. Autier P. Boniol M. Heanue M. Colombet M. Boyle P. Estimates of the cancer incidence and mortality in Europe in Ann Oncol 2007;18: Hill C. Benhamou E. Doyon F. Trends in cancer mortality. Lancet 1990;336: Levi F. Lucchini F. Negri E. Boyle P. La Vecchia C. Cancer mortality in Europe and an overview of trends since Int J Cancer 2004;110: Parkin. D.M.. Whelan. S.L.. Ferlay. J.. and Storm. H. Cancer Incidence in Five Continents. Vol. I to VIII. IARC CancerBase No. 7. Lyon WHO Statistical Information System (WHOSIS). Mortality Database. Available from accessed March

18 5. Burden of cancers attributable to certain risk factors, Serbia 2000 Table 2 shows ranks of 18 health disorders, by sex, based on u Disability Adjusted Life Years (DALYs) from the 2000 Serbian Study of Burden of Diseases and Injuries. Results of the study suggest that the total burdens of malignancies in men and women were 21.07%, and 22.03%, respectively. In the total ranking of 18 selected diseases and injuries based on DALY in 2000 in Serbia, lung cancer ranked 3, colon and rectum cancer 7, breast cancer 8, and stomach cancer 10. The burden of cancer in men is predominated by lung cancer, which is followed by colorectal cancer and stomach cancer. In our female population the cancer burden is predominated by breast cancer, which is followed by lung cancer, colorectal cancer, cervical cancer and stomach cancer (Table 2). Table 2. Rankings of DALYs for 18 selected causes by gender, Serbia Male Female Rank Cause %* Cause %* 1 Ischemic heart disease Cerebrovascular disease (Stroke) Cerebrovascular disease (Stroke) Ischemic heart disease Lung cancer Unipolar depressive disorders Road-traffic accidents 6.92 Breast cancer Self-inflicted injuries 6.34 Diabetes mellitus Unipolar depressive disorders 5.49 Lung cancer Diabetes mellitus 4.93 Colorectal cancer Colorectal cancer 4.47 Cervix uteri cancer Stomach cancer 3.11 Nephritis and nephrosis Birth asphyxia and birth trauma 2.33 Road-traffic accidents Nephritis and nephrosis 2.14 Self-inflicted injuries Asthma 2.11 Stomach cancer Low birth weight 0.73 Asthma Tuberculosis 0.70 Birth asphyxia and birth trauma HIV/AIDS 0.35 Low birth weight Vision and Hearing Loss 0.30 Vision and Hearing Loss Breast cancer 0.09 Tuberculosis HIV/AIDS 0.19 * % of Total DALYs for selected 18 causes The total burden of selected malignancies attributable to smoking, alcohol, physical inactivity and obesity is presented in Table 3. Results of the study suggest that smoking accounted for 84.3% of the lung cancer burden and 9.58% of the cervical cancer burden. Physical inactivity accounted for 26.0% of the lung cancer burden and 15.1% of the breast cancer burden. Results of 18

19 the same study also indicated that obesity was responsible for 14.4% of the colorectal cancer burden and 6.4% of the breast cancer burden, while alcohol drinking accounted for 8.5% of the breast cancer burden. Table 3. Total burden of selected cancers attributable to risk factors (in percents), Serbia, Conditions Risk factors % of total DALYs attributable to risk factors Cancers Lung cancer Tobacco Cervix uteri cancer Tobacco 9.58 Breast cancer Alcohol (harm) Physical inactivity Obesity Colon and rectum cancers Physical inactivity Obesity References Atanasković-Marković Z, Bjegović V, Janković S, Kocev N, Laaser U, Marinković J, et al. The Burden of Disease and Injury in Serbia. Belgrade: Ministry of Health of the Republic of Serbia; International Agency for Research on Cancer. IARC. Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol 83. Tobacco Smoke and Involuntary Smoking. Lyon. IARC

20 6. Selected cancer risk factors in Serbia Smoking, excessive alcohol consumption, obesity, irregular diet and physical inactivity are the leading risk factors in the Serbian population. The listed risk factors are common for numerous chronic noncommunicable diseases which, in the light of their multifactorial etiology, are associated with the presence of two or more of the se risk factors. The results of the Serbian 2000 and 2006 Population Health Surveys relating to the prevalence of risk factors attributable to cancer are presented in Table 4. The 2006 Survey has shown that 33.6% of the adult population are smokers, 40.3% drink alcohol every day or occasionally, 18.3% are obese and 59.9% are not sufficiently physically active during leisure periods. In comparison with the previous, 2000 Survey, the 2006 adult Serbian population shows reduction of the smoking prevalence by 6.9%, alcohol consumption by 7.2%. The prevalence of obesity, however has risen by 1% and physical inactivity by 7.8% (Table 4). Table 4. Prevalence of risk factors attributable to cancer in Serbia, for the years 2000 and 2006 Year Prevalence of risk factors (%) Tobacco Alcohol Obesity Physical inactivity References National Health Survey Serbia, 2000 Institute of Public Healt of Serbia, 2000 National Health Survey Serbia Key finding. Belgrade: Ministry of Health, Republic of Serbia;

21 6.1 Tobacco smoking It has been estimated that almost 1.3 billion people smoke tobacco worldwide. The use of tobacco, i.e. smoking, is not only a risk factor for the occurrence of malignant, pulmonary and cardiovascular diseases, but tobacco addiction is a disease in itself. Tobacco smoking is directly responsible for a half of fatal outcomes of chronic smokers globally. Every year, about five million fatal outcomes worldwide are caused by tobacco use. Tobacco control is one of the most costeffective, evidence based health policies. According to the National Cancer Institute, tobacco smoke may be related to 30% of all cancer deaths and 87% lung cancer deaths in the USA. It has also been confirmed that exposure to passive smoking is an important carcinogenic factor for the occurrence of lung cancer (IARC. 2004). The smoking prevalence in Serbia is high. According to the population health survey conducted in 2000 covering the ages of 20 yrs and above, the male prevalence rate (48%) was among the highest in Europe, while the female smoking prevalence was the highest in Europe (33.6%). The survey repeated in 2006 showed that 33.6% adults in Serbia (47.9% men and 33.7% women) smoked tobacco daily or occasionally. In comparison to the previous, 2000 survey, the tobacco smoking prevalence was reduced by 6.9% on the average, i.e. by 9.8% in men and by 3.8% in women. In 2006 the daily smoking habit was present in 27.7% adults, indicating a 6.6% reduction in comparison with Almost one in four women (23.7%) and one in three men (32.5%) were classified as regular (daily) smokers. Out of these regular smokers 66.8% smoked more than 20 cigarettes a day. The average history of smoking of these regular smokers was 18.8 years. In Serbia 5.9% population was classified as occasional smokers. In the same year 61.7% of the population was exposed to smoke at their own homes, which is a 4% reduction in comparison with On the other hand, 44.9% population in 2006 were still exposed to smoke at their place of work in spite of the adopted Law on Prohibition of Smoking Indoors. Although the exposure to smoke at workplace is reduced by somewhat over 10% in comparison with 2000, the information should be taken with a grain of salt, because of rising unemployment in Serbia. According to the global smoking survey among the young conducted in Serbia in 2003 among year old students, the prevalence of smoking among them is also very high: 54.7% of the young aged tried smoking a cigarette at least once; 16.8% girls and 15.5% boys smoked regularly (daily); 21

22 97.4% of the young were exposed to second-hand smoke at home and 91.3% at public places. The fall of smoking prevalence among the population of Serbia after 2000 resulted from a continuous anti-smoking campaign on the national level. Laws on prohibition of sales of cigarettes to under-age individuals and prohibition of smoking g in public places were adopted, and in 2007 the Strategy and Convention of Smoking Control in Serbia were adopted, as well Definition of exposure Tobacco smoking causes cancer of the oral cavity, pharynx, esophagus, stomach, nasal cavity and sinuses, upper trachea, lungs, kidneys, urinary bladder, uterine cervix, and acute myeloid leukemia (IARC. 2004). All forms of tobacco cause cancer. The greatest cancer risk is due to cigarette smoking since cigarette smoke is usually inhaled, but cigars and pipes may be associated with the same risk if the smoke is inhaled. The risk of malignancy is lower in former than in current smokers. Beneficial effect of quitting is evidenced already after five years, and it is progressively increased over time. For the purpose of the study we considered regular smoking of any tobacco product (smokeless tobacco products are not used in Serbia). We divided smokers in respect to their smoking history to the current and former smokers. We disregarded duration of smoking and amount of tobacco smoked Relative risks (RR) for malignancies in smokers The relative risks for malignancies that were used for the calculation of attributive fraction have been taken over from IARC and presented in Table 8. 22

23 Table 8 Relative risks (RR) of cancer of specific organs associated with tobacco smoking, by sex* Men Women Cancer site Current smoking Former smoking Current smoking Former smoking Oral cavity Pharynx Esophagus Stomach Liver Pancreas Larynx Lung Kidney Urinary bladder Cervix uteri * From meta analysis of studies reported in the IARC monograph on tobacco (2004) and Gandini et al. (2007) RRs for former smokers among women were estimated using the rat o of ln (RR current smoker) to ln (RR former smoker) among men that we applied to ln (RR current smoker) for women. When RRs for women were higher than for men or when no RR was estimable for women. the RR for men was used instead For cervix uteri the ratio ln(rr current)/ln(rr former) and the variance used were the average of those of all other sites Data on exposure prevalence In the light of the fact that the latency period for malignancies ranges years, the best thing to do was to use the data on smoking habits of the Serbian population in Since the data was not available, the 1990 smoking prevalence was obtained by interpolation of the data on smoking prevalence from the 2000 Serbian National Health Survey and Countrywide Integrated Noncommunicable Diseases Intervention (CINDI) program conducted since 1985 on the territory of Vojvodina (Table 9). Table 9. Prevalence * of tobacco smoking in Serbia. by sex, 1985 and 2000 Year Prevalence * of tobacco smoking Smokers Ex-smokers All θ Male Female All Ψ Male Female θ Countrywide Integrated Noncommunicable Diseases Intervention (CINDI), N. Sad, Serbia and Montenegro, 2003, population Ψ National Health Survey Serbia, Belgrade, Serbia,

24 According to this estimate, in 1990 the prevalences of male and female smokers were 53.4% and 33.8%, respectively, while there were 14.7% male and 8.4% female former smokers, respectively (Table 10). Table 10. Prevalence of tobacco smoking in Serbia, by sex, 1990 Prevalence * of tobacco smoking Smokers Ex-smokers All Male Female * estimates for 1990 obtained by linear interpolation of smoking prevalence data for 1985 and AF estimates Table 11 presents the AF values (calculated with the estimated 1990 prevalence), number of new cancer cases and cancer deaths that may be attributed to smoking in Serbia in The total of 5277 cancer cases among men (32.6% of total) and 1693 among women (11.8%) were attributable to cigarette smoking. Among all cancer sites attributable to cigarette smoking in Serbia, lung cancer was recorded in 61.5% men and 47.3% women. Table 11. Numbers * of cancer cases and deaths attributable to tobacco smoking in Serbia, by sex, 2005 Men Women Cancer site AF% Cases Deaths AF% Cases Deaths Oral cavity Pharynx Esophagus Stomach Liver Pancreas Larynx Lung Kidney Urinary bladder Cervix uteri Total % of all cancers 32.6% 39.1% 11.8% 14.3% * based on the estimated 1990 cancer prevalence 24

25 Because of high lethality of many cancer sites attributable to tobacco smoking, the corresponding figures for mortality are higher than for the incidence (39.1% of all cancer deaths in men and 14.3% in women). In the light of the fact that the 1985 smoking prevalence which was used for determination of 1990 smoking prevalence was probably higher than the actual one, since it covered the yr population, the AFs were calculated for the 2000 smoking prevalence, as well (Table 12). The AFs, calculated in this manner, suggest that 5124 cases of male cancer (31.6% of total) and 1691 cases of female cancer (11.8%) were attributable to cigarette smoking. The share of lung cancer among all cancer sites attributable to tobacco smoking was 62.3% in men and 47.4% in women. The corresponding figures for cancer deaths were 38.0% and 14.2% in men and women, respectively. Table 13. Numbers * of cancer cases and deaths attributable to tobacco smoking in Serbia, by sex, 2005 Men Women Cancer site AF% Cases Deaths AF% Cases Deaths Oral cavity Pharynx Esophagus Stomach Liver Pancreas Larynx Lung Kidney Urinary bladder Cervix uteri Total % of all cancers 31.6% 38.0% 11.8% 14.2% * based on 2000 smoking prevalence As expected, the obtained AF estimates, as well as numbers of new cancer cases and cancer deaths attributable to cigarette smoking in Serbia (2005) were similar to the 1990 data obtained with by linear interpolation and those on smoking prevalence obtained in the 2000 Serbian National Health Survey (Tables 11 & 12). 25

26 Indirect AF assessment The relative risks taken over from IARC publication were based on the results of meta analysis comprising a large number of studies conducted in the USA or Nordic countries, so that one may question whether the smoking habits of these population are comparable to the smoking habits of Serbian population. Therefore, we applied an indirect AF assessment. The results of indirect assessment for lung cancer AF (Peto et al.) are presented in Table 14. The method is based on the assumption that since smoking is the main environmental risk factor for lung cancer and since lung cancer is incurable, the lung cancer deaths are a better parameter of the impact of smoking on the occurrence of this disease than the smoking prevalence itself. Hypothetically, we assumed that no cases of lung cancer deaths were attributable to smoking by 1950, and that any increase of lung cancer death after 1950 was attributable to tobacco smoking. The following equation was used for the calculation: AF = (2005 mortality rate 1950 mortality rate) /2005 mortality rate Age-related AF assessment was used for the number of deaths in 2005 for each age group (Table 14). Out of 3522 lung cancer deaths of men registered in 2005 in Serbia, 3362 were attributable to tobacco smoking, corresponding to AF of 95.5%; out of 1021 lung cancer deaths of women registered in Serbia in the same year, 953 were attributable to tobacco smoking, corresponding to AF of 93.3% (Table 14). 26

27 Table 14. Fractions (AF * ) of lung cancer attributable to tobacco smoking in Serbian men and women 2005, calculated by the indirect method Men Age group Mortality rate in 1950 * Mortality rate in 2005 AF (%) All 72.9 *AF for all ages estimated after calculation of AFs for each age category and application of age-specific AFs to the numbers of lung cancer deaths observed in each age category in Source: unpublished death data from National Statistics Office of Serbia and census data of population in FNRY, 1950 Women Age group Mortality rate in 1950 * Mortality rate in 2005 AF (%) All 93.3 *AF for all ages estimated after calculation of AFs for each age group and application of age-specific AFs to the numbers of lung cancer deaths observed in each age group in Source: unpublished death data from National Statistics Office of Serbia and census data of population in FNRY, Discussion Our analysis has shown that tobacco smoking is the main avoidable cause of cancer among both men and women. The impact of tobacco as the risk factor would have been even higher if the calculations had included some rare types of cancer (nasopharyngeal cancer, cancer of the nose and paranasal sinuses, myeloid leukemia) where causative relation with tobacco smoking was evidenced (IARC, 2004), as well as some other types of cancer (colorectal cancer) that are suspected of having the causative relation with tobacco smoking, but without sufficient evidence for such an claim. It is questionable to what extent the data on 1990 smoking prevalence obtained by interpolation are accurate. However, it is the fact that no major differences in AF calculated with estimated 1990 smoking prevalence and AF calculated with smoking prevalence in 2000, provided from the Population Health Survey in Serbia, have been observed. There is also an issue of 27

28 whether the relative risks used for AF calculations, taken over from other populations do correspond to RRs for the Serbian population. Nevertheless, even if the number of cancer cases and cancer deaths attributable to smoking would turn out to be lower than the ones calculated in this study, tobacco smoking would still remain the main avoidable cause of cancer. In the light of the high prevalence of smoking among the Serbian population in 2000, it may be assumed that the incidence of malignancies related to smoking will be still high in the following years. Only after that, the positive effect of reduced smoking prevalence recorded in the period could become noticeable, under the condition that the trend is maintained. References Attributable causes of cancer in France in the year 2000, IARC Working Group Reports Vol. 3, International Agency for Research on Cancer, 2007 The Republic of Serbia strategy for the prevention and control of noncommunicable diseases of the Republic of Serbia. Ministry of Health of the Republic of Serbia. NCD Committee, Belgrade, 2008 Global Youth Tobacco Survey. UNICEF. Ministry of Health of the Republic of Serbia, 2003 Zdravstveno stanje stanovništva Srbije godine, Beograd, 2003 National Health Survey Serbia Key finding. Belgrade: Ministry of Health, Republic of Serbia; 2006 Šaulić A. Atanasković-Marković Z. Burden attributable to major risk factors. In: Atanasković Marković Z. Bjegović V. Janković S et al. The Burden of Disease and Injury in Serbia. Belgrade: Ministry of Health of the Republic of Serbia; Tobacco Smoke and Involuntary Smoking, IARC monographs on the Evaluation of Carcinogenic Risks to Humans, WHO, IARC vol. 83, 2004 Smokeless Tobacco and Some Tobacco-specific N-NitrosaminesSmokeless tobacco, IARC monographs volume 89, 2006 National Center for Health Statistics. Health, United States, 2003 (NHIS Data) 28

29 Mackay J, Eriksen M. The Tobacco Atlas WHO, Geneva Helakorpi S, Patja K, Prattala R, Aro AR, Uutela A. Health behaviour and health among Finnish adult populations, Spring 2003 U.S. Centers for Disease Control and Prevention, Web: Factsheet 98/2, Lung & Asthma Information Agency, Dept of Public Health Sciences, St. George's Hospital Medical School, Cranmer Terrace, London, ww.laia.ac.uk/factsheets/982.pdf WHO European Country Profiles on Tobacco Control

30 6.2 Alcohol drinking Alcohol drinking is an important health and social problem. Pursuant to the 2006 National Health Survey in Serbia, 40.3% of the population drink alcohol every day or occasionally, which is a 7.2% decrease from the 2000 Survey (Table 4). In total, 3.4% of the population, i.e. 7.2% men and 0.4% women drank alcohol regularly, every day. Among the regular drinkers more were 55 years old (16.5%) than below 55 yrs (7.0%). Strong spirits, followed by beer were the favorites among the regular drinkers Alcohol drinking is associated with a series of health disorders. This report focuses only carcinogenic effects of alcohol consumption. Type of alcoholic beverage and frequency of consumption (regularly/occasionally) were disregarded Relative risks (RR) for malignant tumors associated with alcohol consumption Relative risks (RR) for malignant tumors used for the calculation of attributive function are taken over from IARC publication and presented in Table Information used for exposure prevalence Taking into account that self-reported data on alcohol consumption are likely to be underestimated, data from the National Statistics Office on food and beverages consumed in Serbian households were used for estimation of alcohol intake. The year 1992 is the first year for which such data was available. Intake of ethanol for adult persons (15 years of age and above) in grams per day is used as the measure of alcoholic beverage consumption (christianparty.net/globalalcoholeuro.pdf). According to the 1992 data provided by the National Statistics Office (former Federal Republic of Yugoslavia, subsequently Serbia and Montenegro) 9 liters of pure alcohol were consumed per person per year, i.e grams of ethanol per person per day. Since the data on alcohol intake from this study were not distributed by the sex, we used the results published by Institut Nationale de la Statistique et des Etudes Economiques (INSEE, France's National Statistical Office), suggesting that men drank 4.33 times more than women. Using that ratio, the average daily doses of alcohol drank in 1992 were 31.6 grams and 7.2 grams for men and women, respectively. In the calculation of alcohol intake by the sex, we took into account the difference in size between male and female populations (male/female =1.00/0.94). 30

31 6.2.3 AF Estimates According to the calculated AF values 719 cancer cases in men (4.4% of the total number of men affected by malignancies) and 236 cancer cases in women (1.7%) are attributable to alcohol intake. Out of all sites of cancer attributable to alcohol intake in Serbia, oropharyngeal cancer was most common in men (37.0%) and breast cancer (71.2%) in women. Corresponding figures for the deceased were 4.5% of all cancer deaths in men and 1.4% in women (Table 12). According to the available data, alcohol drinking has significantly increased in Serbia over the last 16 years, rising from 19.5 g in 1992 to 56.3 g in Table 11. Relative risks for alcohol drinking and attributable fractions, by sex Cancer Ln (risk per g/d) RR for average consumption # AF% Male Female Male Female Oral cavity, pharynx * Esophagus * Colorectal * Liver * Larynx * Breast # Men: 31.6 g/d ; women: 7.3 g/d (1992) * Based on linear extrapolation from results of meta-analysis (Corrao et al ) Based on results of pooled analysis (Hamajima et al ) Table 12. Number of cancer cases of and deaths attributable to alcohol drinking in Serbia in 2005, by sex Cancer Incident cases Deaths Male Female Male Female Oral cavity, pharynx Esophagus Colorectal Liver Larynx Breast Total % total cancer cases/deaths 4.4% 1.7% 4.5% 1.4% 31