Epidemiologic Study of Gastric Cancer in Iran: A Systematic Review
Authors Kalan Farmanfarma K, Mahdavifar N, Hassanipour S, Salehiniya H
Received 7 April 2020
Accepted for publication 14 September 2020
Published 5 November 2020 Volume 2020:13 Pages 511—542
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Andreas M. Kaiser
Khadijeh Kalan Farmanfarma,1 Neda Mahdavifar,2 Soheil Hassanipour,3 Hamid Salehiniya4
1Department of Epidemiology, Health Promotion Research Center, Zahedan University of Medical Sciences, Zahedan, Iran; 2Department of Biostatistics and Epidemiology, School of Health, Non-Communicable Diseases Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran; 3Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran; 4Social Determinants of Health Research Center, Birjand University of Medical Sciences, Birjand, Iran
Correspondence: Hamid Salehiniya Tel +98 9357750428
Email [email protected]
Background: Gastric cancer (GC) is one of the most common cancers in Iran. Knowledge of the epidemiology of the disease is essential in planning for prevention. So this study aimed to investigate the epidemiological aspects of gastric cancer including prevalence, incidence, mortality, and risk factors of Iran.
Methods: This systematic review study was based on articles published in both English and Persian languages during the years of 1970– 2020 in international databases (PubMed, Web of Science, Scopus) and national databases (including SID, Magiran, and IranDoc). Papers related to epidemiological aspects of the disease including mortality, prevalence, incidence, and risk entered the final review.
Results: According to the studies, the minimum and maximum prevalence of gastric cancer in northwestern Iran (Ardabil) is between 0.2 and 100 per 100,000. Also, the death rate per 100,000 people ranged from 10.6 to 15.72 and the ASMR ranged from 4.2 to 32.2%. On the other hand, the incidence of GC was higher in men than in women (74.9 vs 4.6%). The GC risk ratio was 8-times higher in the elderly than in the other age groups (HR=8.0, 2.7– 23.5). The incidence of gastric cancer in patients with H. pylori infection was 18-times and that of smokers 2-times higher than other populations. Low level of economic situation and food insecurity increased the odds of GC by 2.42- and 2.57-times, respectively. It should be noted that there was a direct relationship between consumption of processed red meat, dairy products, fruit juice, smoked and salty fish and legumes, strong and hot tea, and consumption of salt and gastric cancer incidence. There was also an inverse relationship between citrus consumption, fresh fruit, garlic, and gastric cancer. In addition, the mRNA genes are the most GC-related genes.
Conclusion: Given the high incidence of GC in Iran, changing lifestyle and decreasing consumption of preservatives in food, increasing consumption of fruits and vegetables, and improving the lifestyle can be effective in reducing the incidence of this disease.
Keywords: epidemiology, gastric cancer, Iran, risk factor, systematic review
Gastric cancer is one of the most common cancers in the world,1 with the highest incidence in the countries of Western Asia, Latin America, and the former Soviet Union. The incidence among Japanese, Korean, and Iranian males were 66.7, 64.6, and 30.4%, respectively.2
Gastric cancer, with an annual incidence of 7300, is one of the five most common cancers in Iranian men and women.3 It is the first cause of cancer death in both genders in Iran as most patients are diagnosed at advanced stages of the disease.4 Also, the 5-year survival rate in Iran is estimated to be less than 25%.5
Helicobacter pylori, genetics, gastric ulcer, cigarettes, alcohol, chemical exposure, reflux, chronic anemia, gastric surgery, obesity, radiation, Epstein-Barr virus, gender, race, ethnicity, economic-social status, Type A blood groups, and food play an important role in the risk of gastric cancer.6 Improving living standards and changing dietary habits as well as reducing H. pylori infection are very effective in reducing the incidence of gastric cancer.7 Understanding the epidemiologic status of the disease and associated risk factors are essential for planning to diminish the disease, so this study aimed to investigate the epidemiological aspects of gastric cancer including prevalence, incidence, mortality, and risk factors of Iran.
Materials and Methods
In this study, original articles in the Iranian population which are published in Persian and English language, and published in national and international journals during the years of 1970–2020 with accessible full text, were reviewed.
Articles were selected from international databases (PubMed, Web of Science, Scopus) and national databases (SID, Magiran, and IranDoc).
Papers related to epidemiological aspects of the disease including mortality, prevalence, incidence, risk factors and genetics were reviewed. The results of the studies were presented in separate tables including mortality, prevalence, incidence, and risk factors of genetics.
It should be noted that studies lacking necessary information and links to the topic under discussion were excluded from the study.
Data Collection Process
Abstract and full text of articles, independently, by two relevant researchers, reviewing and listing information prepared for this purpose, including: author’s name, year of publication, place of study, gender, sample size, age incidence, prevalence, and factors. The hazards of the genes in the articles and other cases were recorded in separate tables.
In order to increase the accuracy and reliability of the information and to reduce possible bias, the second review was performed by a second researcher and then registered by both researchers.
Articles related to incidence, mortality, prevalence, risk factors, and genetics were selected in the period of 1970 to 2020 and the results are presented in separate tables.
Synthesis of Results
A total of 3461 articles were initially reviewed. It should be noted that 68 articles were not accessible to the full text, 1823 were duplicate, 822 were fully studied, 593 were irrelevant, and finally 229 were entered (Figure 1).
Figure 1 Flowchart of the included eligible studies in systematic review.
The incidence of gastric cancer in Iran increases due to increasing health level, lifestyle, awareness of early symptoms, and early diagnosis.8 On the other hand, with growth of urbanization, the incidence and consequently the mortality rate will increase.9 One of the causes of the rising incidence of gastric cancer in Iran is related to the diagnosis of end stage (non-curable stage=end stage) disease.10,11
Most patients are diagnosed in advanced stages and cannot be diagnosed at an early stage.12 Studies in most parts of Iran indicate a high prevalence of this disease,13 with the provinces located in the north and northwest as high risk areas and those located in southwestern Iran as medium risk areas.14
Epidemiological studies in Iran show a higher incidence of this disease in men than in women (74.9 vs 4.6), On the other hand, the sudden decrease in the incidence of disease over the age of 80 indicates the limitation of healthcare in this age group in Iran (Table 1). Increasing trend of GC is observed in the majority of men in Tehran province and most women in East Azerbaijan, Markazi, Tehran, and Yazd provinces.15
Table 1 Incidence Rate of Gastric Cancer in Iran
Non-use of refrigerator in some parts of the country, incorrect food preservation methods, high prevalence of H. pylori, and consumption of salty and nitrogen-containing foods, drinking hot tea, smoking and drinking contaminated water, smoking, and opium are important causes of gastric cancer in Iran.16,17 In contrast, in the southern regions of Iran due to high consumption of dates as an antioxidant, the incidence of GC decreases.15
In 2012, the rate of gastric cancer deaths in Iran was 11.4%, and it was reported as the second leading cause of death from common cancers in Iran. In fact, 15.5% of all cancer deaths in Iran are attributable to gastric cancer.18,19 Currently, the highest mortality rate in Southwest and Central Asian countries is observable in Iran (19.9 per 100,000).20
GC is one of the most important causes of cancer death in Iran21 which is due to individual or environmental factors, H-Pylori infection, and gastric atrophy in an Iranian population.22 It should be noted that the incidence of GC mortality has decreased over the last five decades worldwide.15 Thus, the number of deaths due to GC in Iranian military has been steady, which may be due to early diagnosis of this disease.23 ASMR ranged from 4.2–32.2% (Table 2).
Table 2 The Death Rate of Gastric Cancer in Iran
Gastric cancer is one of the most common cancers among Iranian men and women,12 as it become the first common cancer among Iranian men.9 The higher prevalence of males than females can be due to risky occupations such as agriculture, which may lead to exposure to nitrate-contaminated soil and chemical fertilizers as well as men’s genetic susceptibility and, in turn, women’s greater sensitivity to healthcare than men.24,25 The minimum and maximum prevalence of gastric cancer in the previous studies was observed in northwestern Iran (Ardabil) between 0.2–100%. Other provinces were within the mentioned range (Table 3).
Table 3 The Prevalence Rate Of Gastric Cancer In Iran
In Iran, more than 80% of the population over 40 years have a history of H. pylori infection.26,27 H. pylori is the most prominent risk factor for gastric cancer.28 Age of infection seems to be very low in Iran. According to a study in southern Iran, 89% of 9-month-old children and 98% of 2-year-olds have been infected.29 Studies have shown that H. pylori infection has an 18% higher chance of developing gastric cancer than those without the above-mentioned infection (OR=18.58; CI=1.63–221.520)
Cigarette Smoking and Alcohol
Studies show a 25.4% prevalence of smoking among Iranian adults. High smoking in Iran requires special attention as a risk factor for gastric cancer.20 Furthermore, the prevalence of gastric cancer is directly related to the frequency of smoking.9,30
Some surveys in Iran reveal increasing prevalence of cigarette smoking at an early age and subsequently, rising trend of smoking-related cancers is similar to GC.31 According to studies, smoking has a 2-fold chance of developing gastric cancer (OR=2.07; 1.14–3.75) (Table 4).
Table 4 Risk Factors Associated with Gastric Cancer in Iran
Opium has traditionally been used in many Southeast Asian countries, especially Iran.32 It is noteworthy that tobacco use in the north and south of Iran is higher than in other parts of Iran.33,34 According to some investigations in Iran, the chance of gastric cancer in smokers, especially opium consumers, is 3-times higher than those who did not consume (OR=3.0; 1.6–5.6) (Table 4). Because of the risk of hookah, especially for cancer, being less well known and the perception that tobacco is safer than cigarette smoking, the filtration of tobacco in water and the lower cost of hookah than smoking, the tendency for hookah smoking in Iran is increasing.35 Studies show gastric cancer patients are 14% more likely to develop gastric cancer than others (OR=1.14; 0.29–4.42).
In the studies, alcohol consumption increased (OR=2.03; 0.44–9.31) times the chance of developing gastric cancer (Table 4). It should be noted that, due to the legal prohibition of alcohol consumption in Iran, under-reporting may be found in the studied investigations (Table 4).
Low Economic Level and Food Insecurity
In a survey in Iran, farmers and ranchers are considered to be high risk occupations in the prevention of gastric cancer. Findings suggest that gastric cancer is more common in underclass and lower socioeconomic groups.20,36 Increasing food insecurity in developing countries like Iran is due to lower economic levels and rising food costs. As the prevalence of food insecurity in Iran is estimated to be around 50%,37 it is important to note that food insecurity is associated with low economic levels.38 Because of the fat that income is an important factor to access adequate food in the community, people with higher economic status can have more choice in their diet.39 For this reason, Iranian policymakers have emphasized the need to improve the economic status by the resistance economy.40 Based on studies of low levels of economic and food insecurity, the odds of developing gastric cancer by 2.42- and 2.57-times is increasing, respectively (Table 4).
Family History and Blood Type A+
Family history is an important predictor of gastric cancer. Families with a history of gastric cancer have unique clinical manifestations.41 Disease among young people of Iranian families with gastric cancer emphasize the role of family history in disease.42 At the same time, family members experience similar environmental and lifestyle conditions. Family history of gastric cancer may not necessarily be related to genetic effects,43 because environmental factors such as H. pylori infection play a more important role than genetic effects.44 In the studied investigation, family history increased 2.12-times the chance of developing gastric cancer (Table 4). According to the studies, the prevalence of blood type A in an Iranian population is 30.25%.27,45 In this survey, blood group A+ was 18.8% (Table 4).
Epstein-Barr Virus (EBV) and HTLV-1
EBV prevalence in gastric cancer patients ranged from 6.25–6.6% (Table 4). Studies in Iran show low prevalence of EBV among GC patients.46 This is estimated to be between 3–6.66%.47 The differences in EBV abundance reflect socio-economic, health and cultural differences in individuals,48 hence the relationship between incidence of GC and EBV in different regions may reflect epidemiological and clinical-pathological factors, dietary habits and, ultimately, genetic differences.49 Epidemiological studies indicate HTLV-1 is endemic in some part of Iran such as Khorasan, where HTLV are reported as around 0.77–1.7% in blood donors of different regions.50 The prevalence of blood group A was 18.8% (Table 4).
Studies have shown an inverse relationship between citrus fruits, fresh fruits, garlic consumption, and gastric cancer (Table 4). Fruits are rich in antioxidants due to their fiber, vitamins, and minerals that can prevent initiation or progression of cancer.51–53 Ascorbic acid and carotene in vegetables and fruits can eliminate nitrite.54 Consuming some vegetables such as onions less than twice a week does not have any protective effect for this cancer (OR=1.28; 0.73–2.23). This is ambiguous, but may be related to the constituents of the soil (Table 4).
According to several studies, there is also a direct relationship between consumption of processed red meat, dairy products, fruit juice, smoked and salty fish, grain, strong and hot tea, and salt consumption, with a chance of incidence of gastric cancer (Table 4). Meats that are cooked at high temperatures such as frying and kebabs produce various types of carcinogens such as polycyclic aromatic hydrocarbons that cause gastric cancer.56 Also, salt by stimulating and damaging gastric mucosal tissue is effective in the development of gastric cancer.55 It should be noted that canned foods, spicy pickle, and animal protein are the dominant food among Iranian populations.56 Pickles are an important risk factor for gastric cancer due to their high salt and nitrate compounds. It should be noted that the ingredients of pickles vary from country to country due to the amount of vegetables, salt and acidity.57
Studies have found a direct relationship between pickling and gastric cancer (Table 4) (OR=1.47; 0.84–2.58). Some surveys in Iran show low levels of selenium in gastric cancer patients.58 The protective effect of selenium on cancer may be due to oxidative stress and DNA damage reduction, recovery of damaged DNA and apoptosis through the p53 tumor suppressor gene and induction of Phase II enzymes to detoxify carcinogenic cells.59 Investigations show protein intake reduces the chance of gastric cancer (Table 4). High protein intake in a low-income Iranian rural population indicates a healthy lifestyle.60 In addition, vitamins and minerals play an important role in preventing tumorigenesis. Iron or detoxification of oxidative free radicals can prevent DNA damage.61 Irregular food intake appears to cause gastric ulcers, which is not unexpected if gastric cancer is not treated in the long-term. The findings of the studies confirm the above (Table 4).
GC is more common in people over 50 years of age62 and is more common in people between the ages of 70 and 80 years. The incidence of GC is also increasing at ages younger than 20 and 40 years.63 In general, the highest incidence of GC is observed in the fifth and sixth decades of life, while the risk is reduced at ages younger than 44.15 According to some investigations, the risk ratio of GC in older people is eight times higher than in other age groups (HR=8.0; 2.7–23.5) (Table 4).
Achalasia is the most well-known esophageal motor disease. Many patients are treated for gastroesophageal reflux disease before detection of achalasia. Gastric adenocarcinoma is the most common malignancy causing pseudo-achalasia.64 In conducted surveys, patients with achalasia are 97% more likely to have GC other than those who do not have achalasia (Table 4).
Unwashed Hands After Defecation
Studies show that unwashed hands increase the odds of developing gastric cancer by 2.61-times (OR=2.61; 1.43–4.76) (Table 4). In recent decades, hand-eating has become very common in Iranian culture. Although it is good to wash your hands with water, it is not enough to eliminate contaminated microorganisms after excretion or exposure to toxic substances. Due to the frequent stool excretion and improper hand washing, the emergence of diseases associated with infected microorganisms (H.pylori) such as gastric ulcer or gastric cancer are expected.65
History of X-Ray Dye Exposure and History of CT Scan Encounter
The use of modern technology such as computed tomography and radiography in the diagnosis of diseases has been widely observed in recent decades, irrespective of its side-effects and subsequent consequences.66 According to the study, the odds of developing gastric cancer as a consequence of advanced technology are 91% and 39%, respectively (Table 4).
mi-RNAs are a subset of non-coding RNAs that contain approximately 22 nucleotides. They also play important functions in various cellular processes including differentiation, proliferation, and apoptosis; furthermore, they play an important role in the development of some cancers, including GC.
Disruption in the regulation of genes such as miR-383 is associated with cancer.67 It appears that more than one-third of the genes encoding human protein are controlled by mi-RNAs and have their genetic pathways exerting their effects.68
In H-pylori-infected individuals, IL-18mRNA and IL-18 levels in gastric mucosa are increased,69 so that IL-18 cytokines increase inflammatory conditions in chronic diseases with immune pleiotropic function,70 and directly increase the IL-1, IL-6, and TNF-a cytokine from macrophages, promoting GC progression.71 According to research, mi-RNAs group genes are the most GC related genes (Table 5).
Table 5 Genes Associated with Gastric Cancer in Iran
Given the high incidence of GC in Iran, changing lifestyle and decreasing consumption of preservatives in food, increasing consumption of fruits and vegetables, and improving lifestyle can be effective in reducing the incidence of this disease.
The authors report no conflicts of interest in this work.
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