The present study was designed and implemented to estimate and project premature mortality rate of GI cancers in Iran from 2001-2030. The results demonstrated that the mortality rates in all GI cancers are higher in males than in females. Also, it was shown that the trend of mortality rates for GI cancers were decreasing until 2015 but it will remain stationary among males into 2030; whereas by the same year, females will experience an ascending trend in mortality rates. Our study revealed that the highest mortality rate is associated with stomach cancer in both sexes, which its decreasing trend will continue to 2030. Also, esophageal and colon and rectal cancers will have a downward trend; however, the trend of pancreas, gallbladder and liver cancers will be upward for both sexes.
Cancer is still one of the most important public health problems in Iran, claiming tens of thousands of lives each year. Gastrointestinal cancers have been introduced as dangerous and deadly cancers in the country over the past decades [12]. The results of the present study were not consistent with some of the studies carried out in this field. For example, the study by Pourhoseingholi M et al. carried out to assess mortality rates and trends of GI cancers in Iranian population from 1995 to 2003, indicated that the mortality rates of GI cancers were either increasing or slightly stationary from 1995 to 2003; also, their study showed that the mortality rates for all gastrointestinal cancers were higher in males than in females [13]. In the same study, the mortality rate of colorectal cancer demonstrated a modest increase over the period of 1995 to 2003, but stomach and esophageal cancers were undergone a sharp increase in the trends. Plus, the mortality rate of pancreatic cancer decreased slightly during the studied time-period [13].
In contrast, the results of many studies were consistent with those of our study. Some studies performed in European countries have shown that the mortality rates of stomach and colorectal cancers are, in fact, decreasing [14, 15]. In the United States, the incidence and mortality rates of colorectal cancer have been showing declining trends; also, the mortality rates from this cancer in the European Union have been decreasing as well; however, its incidence and mortality have been increasing in Eastern Europe [16, 17]. The study done by Ana Ferro et al. to determine the worldwide trends in stomach cancer mortality from 1980–2011 and its prediction until 2015, indicted that the patterns and trends of stomach cancer mortality have been declining in most countries over the past few years [18]. Another study also showed that stomach cancer related mortality has been decreasing since the 1970s, and the rate is projected to decline in the next decades in Portugal [19]. The study performed by Gaëtan-Romain Joliat et al. to estimate incidence and mortality rates of esophageal, stomach, pancreatic, liver and colorectal cancers by 2030 in Switzerland demonstrated the mortality rates of esophageal, pancreatic and liver cancers will be either stationary or on the slight rise. In contrast, the trend of stomach and colorectal cancer will undergo a significant decrease [20]. As observed, the results of most studies conducted in this area are consistent with those of our study. Generally, reduction of the prevalence of H. pylori infection, decrease in tobacco consumption, improvement in socio-economic situation, development of food preserving means, and improvement of screening and detecting methods as well as timely treatment may be the major causes of the decreasing trend of mortality rates of stomach cancer and the other gastrointestinal cancers in most countries around the world [21-24]
Another study conducted in Shanghai to investigate the trend of liver cancer from 1973 to 2012 and project it into 2020. The results showed a 50% decrease in the mortality rate of this cancer by 2012. The decrease was projected to continue until 2020 [25]. In the United States, it has been shown that the mortality rate of liver cancer is increasing and this increase is more prevalent among younger age groups [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. Young age, gender, exposure to aflatoxin B1, alcohol consumption, smoking, and unhealthy diet are demographic and environmental factors affecting mortality of liver cancer [27]. Also, obesity and diabetes have big impacts on fatty liver and ultimately liver cancer [28, 29]. In a study by the same researchers who carried out the present study, it was shown that obesity and diabetes in Iran are on the rise and this trend will continue in the future which can be one of the factors contributing to the increased number of in liver cancer among Iranian population [30]. Another reason is the lack of vaccination among 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 increased obesity prevalence in both sexes [30], it can be considered as one of the factors in the increasing trend of gallbladder cancer mortality, especially among females. Since the prevalence of obesity in females is higher than in males, 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, directly, be attributed to it. On the other hand, the trend of diabetes is on the rise 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 Iranian provinces. Given that studies on the geographic distribution of cancer related deaths in Iran are limited, in the present paper, those studies that address the geographical distribution of the cancer incidences are mentioned. Studies have shown that 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 at the world level [34, 35]. The causes of high incidence of esophageal cancers in these areas may be traced to drinking hot tea, low intake of fruits and vegetables, poor socio-economic status, and opium consumption [36, 37].
The other study conducted 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. Also, generally a wide geographical variation was observed between the Iranian provinces [38]. Studies have shown that colorectal cancer incidence is not distributed uniformly across all geographic units [39, 40]. Some studies have shown that colorectal cancer incidence rate in the north of Iran is higher than in the south of the country [41].
In another study carried-out by Mohebbi M et al. to determine geographical spread of gastrointestinal cancers incidence rates in the Caspian Sea region of Iran, the results showed that 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 cancers in both sexes. The same study showed that the pancreatic cancer prevalence is low and there was not enough evidence to assess the spatial correlations [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 suffer from higher incidence of stomach cancer compared to the deserts and southern regions [43]. Also, another study that amid at spatial analysis of gastrointestinal cancer incidence rate in Iran using Poisson Kriging showed that the north and northwestern regions of the country have higher incidence of gastrointestinal cancer compared to the deserts and southern regions [44].
The comparison of GI cancers mortality rates in the present study with those in the other studies gives an insight into the core of the discussion. In the study by Pourhoseingholi MH et al. to determine the mortality rates and trends of GI cancers in Iran from 1995 to 2004, it was showen that the overall GI cancers mortality rate was increased from 16.06 in 1999 to 19.03in 2003 per 100000 individuals; this trend underwent a slight decrease in 2004. Also, the rate was higher among males and increased as the age increased. In the study, the highest mortality rate was associated to gastric cancer which was increased from 1.68 in 1999 to 8.78 per 100000 individuals in 2003; however, the rate was slightly decreased between 2002 and 2004. The mortality rate of CRC cancer moderately increased from 0.46 in 1999 to 3.15 in 2003 per 100000 individuals; however, this was decreased between 2003 and 2004 as well. Likewise, the rate for esophageal cancer moderately increased from 0.73 in 1999 to 4.28 in 2002 per 100000 persons but drpped between 2003 and 2004. According to the study, from 2003 onwards, all cancers have shown a decreasing trend [13]. Another study by Salimzadeh H et al. conducted 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. 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 seen, the results of these studies are consistent with those of the present 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 took place in the cancer risk factors [48].
Mortality trend, in fact, results from combination of incidence and survival trends. Incidence trend reflects changes in the prevalence of risk factors and screening strategies; while survival trend depends on 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 the risk factors such as improve in lifestyle, reduction of tobacco use, improve in diet by consumption of high amounts of fresh fruits and vegetables and employ new methods of food preservation. Also, the treatment of Helicobacter pylori infection may play an important role in reducing stomach cancer; some studies have shown that giving antibiotics to patients 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 cancer treatment and screening strategies have played a key role in increasing survival rate and reducing the mortality rate from cancers. For instance, studies have shown that after using screening system by testing for occult blood in the feces, deaths from colorectal cancer in many European countries have dropped significantly over the past years [51, 52]. In general, screening programs for gastrointestinal cancers, such as colorectal cancer, may lead to the diagnosis of treatable precancerous lesions and, thereby, 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 rate are of significant importance to the policy makers and community health planners. Geographic distribution of incidence, prevalence and mortality are key factors in identifying and preventing risk factors. Geographic analysis of disease rates can play an important role in allocating resources, facilities and manpower as well as formulating and evaluating etiological assumptions and interventional measures in areas that require special attention [54]. Therefore, given the limited number of studies conducted in Iran on the geographical distribution of cancer related mortality, further studies are suggested to be performed 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, due to changes 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 the 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 may vary. It should also be noted that this study is part of a larger study aimed at the health impact assessment in Iran. The larger study includes the estimation of 6 risk factor trends and related avoidable deaths. The overall report is hoped to be employed for high-level policymaking in the country.