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 [12]. 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 [13]. 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 [13].
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[14, 15]. 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[16, 17]. 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 [18]. 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 [19]. 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[20]. 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[21-24]
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 [25]. 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 [26]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 [27]. Also, obesity and diabetes have big impact on fatty liver and ultimately liver cancer [28, 29]. 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 [30]. 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 [31]. Given the increase in obesity in both genders [30], 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[32]. In another study, the association between diabetes and pancreatic cancer has been confirmed [33]. 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 [34, 35], 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[36, 37].
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 [38]. Studies have shown that colorectal cancer incidence is not uniform at the level of different geographic units [39, 40]. Also, some studies have shown that colorectal cancer in the north of Iran is higher than the south [41].
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 [42]. 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 [43]. 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 [44].
In this part of the discussion, we compare the mortality rate of GI with other studies in this regard. In study by Pourhoseingholi MH et al. aimed to determine the mortality rates and trends from GI cancers in Iran from 1995 to 2004 showed that the mortality rate due to all GI cancers was increased from 16.06 in 1999 to 19.03 per 100000 in 2003 and slightly decreased in 2004. The rate was higher for men and increased as age increased. The highest mortality rate belongs to gastric cancer which was increased from 1.68 in 1999 to 8.78 per 100000 in 2003, however, it had slight reduction between 2002 and 2004. The mortality rate of CRC cancer moderately increased from 0.46 in 1999 to 3.15 per 100000 in 2003, however, decreased between 2003 and 2004. Likewise, for esophageal cancer moderately increased from 0.73 in 1999 to 4.28 per 100000 in 2002, however, declined between 2003 and 2004. In this study, from 2003 onwards, all cancers have shown a decreasing trend [13]. Another study by Salimzadeh H et al. aimed to evaluate the annual trends of GI Mortality in Iran during 1990-2015 indicated that the ASMR for gastric, esophagus, liver, and colorectal cancers were 20.5, 5.8, 4.4, and 4.0 per 100 000 persons-years , respectively between 1990 and 2015. Overall, a declining trend was observed for the annual mortality of GI cancers [45]. Additionally, the same declining pattern has been observed in many countries around the world for these cancers [46, 47]. As can be seen, the results of these studies are consistent with the results of our study. Various studies have suggested that the causes of this annual mortality of GI cancers are due to access to screening or prevention services and changes in the risk factors for these cancers[48].
Trends in mortality result of the combination of trends in incidence and trends in survival. Incidence trends reflect changes in risk factors and screening strategies, while survival depends of screening strategy and changes in treatment efficacy. In the present study, a dropped was observed in the mortality of stomach, colon and rectum, and esophageal cancers, which may result from changes in risk factors such as 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 [49, 50] Additionally, advances in cancers treatment and screening strategies have played an important role in increasing survival and reducing the mortality rate of cancers. For example, studies have shown that deaths from colorectal cancer in many European countries have dropped significantly over the past week after using screening system by testing for occult blood in the fecets [51, 52]. In general, screening programs for gastrointestinal cancers, such as colorectal cancer, can be lead to the diagnosis of treatable precancerous lesions and a reduction in mortality trend. Therefore, the implementation of screening programs in high- and medium-risk populations for gastrointestinal cancers should be considered as an important priority for health system policymakers [53].
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 [54]. 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. Finally, our predictions can be sensitive to the choice of model type and set of assumptions. If the assumptions are not met, the predictions can be different. It should also be noted that this study is part of a larger study aimed at the health impact assessment in Iran which has estimated the trend of risk factors (6 risk factors) and avoidable deaths due to each of them for different diseases and a policy report is for high-level policymakers in the country.