Premature Mortality of Gastrointestinal Cancer in Iran: Trends and Projections for 2001–2030

Abstract

Introduction

Cancer is one of the main causes of death in the world as well as Iran [1, 2] and Gastrointestinal (GI) cancers are considered to be the fourth most common cancers [3]. GI cancers are the first cause of cancer-related deaths in males and the second cause of cancer-related deaths among females in Iran [4]. It includes a wide range of cancers with different causes. Esophageal, colon and rectum, gallbladder, pancreases, stomach, and liver cancers are the most common GI cancers.

GI cancers can lead to years of life lost from premature death, disability, and increased burden of disease. It has significant socio-economic effects on population. Premature death is one of the indicators used for studying the impacts of screening programs, early detection, and prognostic factors. Also, it can play an important role in health decision made in communities [5]. Planning for future is an important part of cancer control and prevention programs. Although the prediction of the incidence and mortality of cancers is largely associated with uncertainty, these predictions can be employed by health planners in assessment and appropriate allocation of resources, prevention, and treatment. It also enables healthcare policymakers to study the results of interventions in reducing cancer and its consequences. To project future cancer mortalities, especially GI cancers, many statistical models have been presented over the past few decades that often provide reasonable and appropriate predictions when applied to recent trends [6,7].

Therefore, considering the importance of modeling for project future cancer mortality especially GI cancers on one hand and the rarity of studies on modeling GI cancers in Iran on another, this study was conducted to evaluate premature mortality trend and projection of GI disorders by 2030 in national and subnational levels in Iran. This evaluation can be used for health planning and policy making. 

Methods

Study Area

The trend in the rate of premature death due to GI cancers at national and subnational levels was obtained through Death Registry System (DRS) (2001-2015). Premature mortality rate of GI cancers was projected through the spatio-temporal model to 2030 by sex, province and cancer type.

Death Data

Death data was gathered from the DRS. The death registration system records death information based on international classification of diseases 10 (ICD10) and death certificates. More details can be found elsewhere [8]. These data usually have a degree of incompleteness and misclassification. These problems were corrected at the Non-Communicable Disease Research Center of Tehran University of Medical sciences (NCDRC); details in this regard are provided elsewhere [8]. In this study, the recorded death data was derived based on the IHME GBD codes (B.1.1, B.1.2, B.1.3, B.1.10, B.1.14, B.1.15), which is equivalent to the C00 to C97 codes in the ICD10. The studied cancers were esophageal, colon and rectum, gallbladder, pancreases, stomach, and, liver.

Premature deaths are referred to deaths occurred at the age of 30-70. Cancer data was used in 8 age groups at intervals of 5 years (35-39, 65-69) from 2001 to 2015 annually by sex and province. Death rate was standardized for age through the direct method.

Population and Covariates Data

Demographic data was obtained from statistical censuses and yearbooks and, using spectrum software, were projected by 2030. The covariates of wealth index, urbanization, and years of schooling were also extracted from the household and expenditure surveys and were projected, with the spline model by 2030, to be used in modeling.

Spatio Temporal Model

Spatio temporal model was used to project spatial and temporal correlations by 2030. For this, the random effect model was first implemented. In the random effect model, the dependent and independent variables were mortality rate logit and time respectively. Correlation between the provinces was considered to be autoregressive 1. Then, the covariates of urbanization percentage, wealth index, and number of years of education entered into the model. In the next step, time and space residuals were added to the projections. Finally, mortality rate was obtained according to province and sex for each cancer. Simulation was carried out to achieve a 1000 iteration. All analyzes were performed using R version 3.5.1 software (02-07-2018).

Results

The results showed that the mortality rate of gastrointestinal cancers were higher in males than in females. The overall mortality rates for cancers in males were 6.1 (5.2-7.0) and 3.9 (3.4-4.5) per 100000 in 2001 and 2015 respectively. The corresponding values for females are 3.8 (3.3-4.4) and 3.1 (2.4-2.7) per 100000. The mortality rate of gastrointestinal cancers by 2015 has been decreasing but it will remain stable by the year 2030 (3.9 (3.4-4.5)) in males; whereas, the rate will be increasing in females (3.7 (3.2-4.2)). It worth mentioning that the trend of each cancer varies.

The highest mortality rate, in both sexes, is associated with stomach cancer, which has had a decreasing trend which will be continued. The mortality rate from stomach cancer in females was 5.4 (6.2- 4.7) per 100000 in 2015, and it is projected to be 2.5 (2.2- 2.9) per 100000 by 2030. The corresponding values in male are 10.2 (8.9-11.5) per 100000 and 4.7 (4.1- 5.4) per 100000 respectively. Also, esophageal and colon and rectum cancers will have a decreasing trend; whereas, the trends of pancreatic, gallbladder, and liver cancers will be increasing. This pattern is the same for both males and females (Figures 1 and 2) and Gallbladder cancer is expected to increase more severely in females. 

In 2001, GI cancers were distributed uniformly in the Iranian provinces and hardly indicated any variation; the highest mortality rates of GI cancers were related to esophageal, colon and rectum and stomach and the lowest rates were due to the gallbladder, pancreases and liver cancers. Of course, the distributions were somewhat different and the variation between provinces was clearer in 2015, so that the esophageal, colon and rectum, pancreatic and stomach cancers had the highest mortality rates of GI cancers and were mostly related to the central provinces of the country. By 2030, GI cancers were, also, distributed uniformly in the Iranian provinces level and there was no particular variation. The highest mortality rates of gastrointestinal GI were related to gallbladder, pancreases and liver, and the lowest rates due to esophageal, colon and rectum and stomach cancers (Figure 3).

 The mortality rates of esophageal cancer is expected to decrease sharply for all provinces especially southern and southeastern regions by 2001 to 2030. This substantial reduction is also expected for colon and rectum cancer in all provinces especially northwest, south and south east regions. Similarly, a significant reduction is also expected for stomach cancer in all provinces especially west, northwest, east and south east regions by 2001 to 2030. In contrast, the mortality rates of gallbladder cancer is expected to increase sharply in all provinces especially  north, west, southwest, east and southeast regions by 2001 to 2030 . For pancreases cancer, this substantial increase is also expected in all provinces especially central, west, southwest and east regions. In the same way, this increase is also expected to be significant for liver cancer in all provinces especially north, southwest, east and southeast regions by 2001 to 2030 (Figure 3).

The mortality rate in each province by type of the cancers and their change percent from 2015 to 20 are shown in Table 1.

Discussion

The present study was designed and implemented to estimate and project premature mortality rate from GI cancers in Iran from 2001-2030. The results demonstrated the mortality rate for all GI cancers in males is higher than females. Also the trend of mortality rates for GI cancers has been decreasing by 2015, but this trend will be steady in males until 2030; however, it will be ascending in females. Our study revealed the highest mortality rate is related to stomach cancer in both sexes, which has a decreasing trend and will continue. Also, esophageal and colon and rectal cancers will have a downward trend, however, the trend for the cancers of pancreas, gallbladder and liver will be increased and this pattern is the same for females and males.

Cancer is still one of the most important public health problems in Iran and gastrointestinal cancers have been introduced as dangerous and deadly cancers [9]. These results were not consistent with some of the studies carried out in this field. For example, the study by Pourhoseingholi M et al. with the aim of assessing mortality rates and trends from GI cancer in Iranian population from 1995 to 2003, showed mortality for GI cancers has been increasing or stabilized during from 1995 to 2003, also the mortality rates for all gastrointestinal cancers were higher for males than females [10]. In the same study, the mortality rate of colorectal cancer showed a modest increase over the period 1995 to 2003, but stomach and esophageal cancers showed a sharp increase in their trends. In contrast, the mortality rate of pancreatic decreased slightly during the years while under study [10].

In contrast, the results of many studies were consistent with our study. Some studies in European countries have shown that mortality rates of stomach and colorectal cancers are decreasing [11, 12]. In the United States, the incidence and mortality of colorectal cancer has trend toward declining and its mortality in the European Union was also decreasing. However, its incidence and mortality is increasing in Eastern Europe [13-14]. The study by Ana Ferro et al. to determine the worldwide trends in stomach cancer mortality from 1980–2011, and its prediction until 2015, indicted that patterns and trends of stomach cancer mortality is declining in most countries of the world during the last few years [16]. Another study also showed that stomach cancer mortality has been decreasing since the 1970s, and rates are projected to decline in the next decades in Portugal [17]. The study by Gaëtan-Romain Joliat et al. to estimate incidence and mortality rates of esophageal, stomach, pancreatic, liver and colorectal cancers up to 2030 in Switzerland demonstrated the mortality rates of esophageal, pancreatic and liver cancers will experience stable or slightly rising trend. In contrast, stomach and colorectal cancer will experience a significant decrease [18]. As can be seen, the most studies are consistent with our study results. Generally, the reduction of prevalence of H. pylori infection , tobacco consumption , improving the economic -social situation, development of food storage status and improvement of screening and detects methods and timely treatment in the most countries in the world may be a major causes to reduce the mortality rate of stomach cancer and other gastrointestinal cancers [19-22].

A study in Shanghai investigated the trend of liver cancer from 1973 to 2012 and projected it by 2020. The results showed a 50% decrease in the mortality rate of this cancer by 2012; and the decrease will go on until 2020 [23]. Also, In the United States, it has been shown that mortality rate from liver cancer is increasing, and this increase is higher in younger ages [24] which is consistent with the results of the present study. The increase in this cancer can be explained by the demographic, environmental and lifestyle factors. Younger age, gender, exposure to aflatoxin B1, alcohol consumption, smoking, and unhealthy diet are demographic and environmental factors that affect mortality of liver cancer [25]. Also, obesity and diabetes have big impact on fatty liver and ultimately liver cancer [26, 27]. In a study by researchers who carried out the present study, it was shown that obesity and diabetes in Iran are increasing and this trend will continue in the future which can be one of the factors contributing to the increase in liver cancer among Iranian population [28]. Another reason is the lack of vaccination in the age group of 30-70 year olds. Vaccination of hepatitis B in Iran has been included in the vaccination program for the newborns since 1993.

Gallbladder cancer is associated with obesity [29]. Given the increase in obesity in both genders [28], it can be considered as one of the factors in the increasing trend of gallbladder cancer mortality, especially in women. Since the prevalence of obesity in women is higher than in men, there may be another unknown risk factor in the incidence and mortality of this cancer that should be investigated in further studies. 

A study found that smoking is an important risk factor in pancreatic cancer [30]. In another study, the association between diabetes and pancreatic cancer has been confirmed [31]. The trend of smoking in Iran is declining and the increase in pancreatic cancer cannot be certainly attributed to it. On the other hand, the trend of diabetes is increasing and it can be considered as a factor in the increasing trend of pancreatic cancer.

The present study indicated that there is geographical variation in different provinces in Iran. Given that studies on the geographic distribution of cancers deaths in Iran are limited, inevitably, studies that address the geographical distribution of the incidence of cancers are mentioned. Studies have shown the north and north east regions of Iran are high-risk areas for esophageal cancer, even one of these provinces (Golestan) has a high incidence in the world level [32, 33], the causes of high incidence of esophageal cancers in these areas drinking hot tea, low intake of fruits and vegetables, low socioeconomic status, and opium consumption have been mentioned [34, 35].

The study by Khosravi Shadmani F et al. to determine geographic distribution of the incidence of colorectal cancer in Iran, showed that the highest incidence rates of colorectal cancer were found in the central, northern, and western provinces of Iran. But, in general the wide geographical variation was observed at the level of the provinces of the country [36]. Studies have shown that colorectal cancer incidence is not uniform at the level of different geographic units [37, 38]. Also, some studies have shown that colorectal cancer in the north of Iran is higher than the south [39].

Another study by Mohebbi M et al. to determine geographical spread of gastrointestinal tract cancer incidence in the Caspian Sea region of Iran, the results showed that non-random spatial patterns for gastric and esophageal cancers are similar in both sexes. Also high-incidence clusters were discovered for esophageal, stomach, and colorectal and liver cancer in both sexes. In the same study showed that the pancreas cancer have low prevalence and there was not enough evidence of spatial trends [40]. In another descriptive study by Sadat Asmarian N et al. conducted to the map stomach cancer rate in Iran using area-to-area Poisson Kriging, the results indicated that the north and northwestern regions of Iran have a higher incidence of stomach cancer than the desert and southern regions [41]. Also, another study with the aim of spatial analysis of gastrointestinal cancer incidence rate in Iran using Poisson Kriging showed that the north and northwestern regions of Iran have a higher incidence of gastrointestinal cancer than desert and southern regions [42].

Generally, as it is seen, a dropped was observed in the mortality of stomach, colon and rectum, and esophageal cancers, which may result from improve lifestyle, reduction of tobacco use, improve diet by consumption of high amounts of fresh fruits and vegetables and more use of the refrigerator to hold foods rather than traditional ones. Also, the treatment of Helicobacter pylori infection can also play an important role in reducing stomach cancer, because some studies have shown that giving antibiotics to people with Helicobacter pylori infection, may reduce the number of pre-cancerous lesions in the stomach and reduce the risk of developing stomach cancer [43- 45].

Today, study of the geographical distribution and estimating the mortality is a matter for policy makers and community health planners. Because geographic distribution of incidence, prevalence and mortality plays an important role in identifying and preventing risk factors. Geographic analysis of disease rates can play an important role in allocating resources, facilities and manpower in addition to formulating and evaluating etiological assumptions and interventional measures in areas that require special attention [46]. Therefore, given the limited studies conducted in Iran on the geographical distribution of mortality from cancers, further studies are needed in this regard. This study is the first investigation carried out at national and sub-national levels to predict the mortality of gastrointestinal cancers in Iran by using corrected and validated mortality data. However, because of the change in made in provincial divisions, the researchers faced some problems that were solved by obtaining information at the district level. Another limitation was the lack of information on the incidence of these cancers.

Conclusion

The results of this study showed that the mortality rate of GI cancers had been decreasing until 2015 but it will remain stable by 2030 in males; whereas the rate will be increasing in females. There was a considerable variation in the mortality trends of different cancers, showing an increasing trend the pancreatic, gallbladder, and liver cancers while a dropped was observed in the mortality of stomach, colon and rectum, and esophageal cancers. Therefore, given the difference in the patterns of GI cancers and their trends around the country, a more comprehensive control plan is needed that includes the predicted variations.

Declarations

Acknowledgments

 This paper was derived from a PhD thesis and was conducted in the Kerman University of Medical Sciences. The authors would like to express their deep appreciation to all those in Non-Communicable Diseases Research Center in Tehran University of Medical Sciences who contributed in conducting this study by providing useful data and valuable comments.

Authors ‘contributions

F KHSH, AK H, and F F designed the study.

AK H and F F supervised the study.

F KHSH and M Y processed the data.

F KHSH, MY, and K M, did the statistical analysis.

F KHSH, AK H, F F, K M, and R KHSH interpreted the results.

F KHSH, AK H, F F, M Y, K M, and R KHSH wrote the original draft.

F KHSH, AK H and F F review and edit the final draft.

Funding

The study was supported by a grant from the Kerman University of Medical Sciences under the grant number of 95000109. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Availability of data and materials

The data is restricted because it is maintained by Ministry of Health and Medical Education (MOHME) of Iran. These information are kept on data servers at the Iranian non-communicable diseases research center (NCDRC) and the researchers are only allowed to extract the results. Since the data are considered nationally confidential, there is no way to access or publish data by third parties. Please contact to: Dr. Farshad Farzadfar Email: [email protected].

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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