The yet growing national incidence rate of GC is already higher than its corresponding global figure. The sex-age-specific incidence rates of GC suggested a clear difference between males and females as GC starts much earlier (even during childhood) in men when compared to women. A traditional explanation for such difference between the two genders is the higher rate of smoking and alcohol use in men than women. However, according to the results of the present study, GC in men is started at younger ages, when exposures to these factors are rare (we don’t expect much smoking or alcohol drinking habits among Iranian children or adolescents) and too close to the outcome (no temporality). On the other hand, our study results suggested that GC starts rising sharply in men (compared to women) at about 40 years of age, an expected time for seeing the causal actions of smoking, alcohol drinking, and drug use in men. According to the results of the current study, it seems that GC among the Iranian population is driven by different factors at different ages.

Since GC is an important and growing multifactorial health issue in Iran, defining the spatial distribution of the disease is of utmost importance. According to the results of our spatial analysis, Ardebil had the highest rate of incidence and the highest rate of raise in the incidence of GC. The province also come with the highest age-standardized incidence rates in both men and women. Previous studies suggested that the high incidence of esophageal cancer in this province (Ardebil) could be due to the presumed belt for upper gastrointestinal tract cancers. Including stomach and esophagus cancers, the belt is originated from the Far East or East Asia and crosses Central Asia and Near East, the geographical location of Iran [14]. It is worth noticing that the distribution of esophageal cancer in Iran is also highly variable. The results of the present study also showed that Ghom had the lowest incidence rate of stomach cancer during the study period. Our estimated rate of change during the study period suggests that all provinces in the northern part of the country were among the provinces with the higher rates of incidence but with a relatively low rate of change in the incidence of GC. The only exception was observed for Ardabil (the province with the highest rates of both incidence and change in the country). The observed upward trend in the incidence rate of GC in Arak (an industrial province in the center of the country) is in accordance with what was reported by Moradzadeh who used local data [15]. The observed patterns of change in the incidence of GC during the study period (10 years) suggests that despite having a relatively higher annual rate of GC incidence, a lower rate of change (raise) is observed (except for Ardabil and Bushehr) in different parts of the country (the rate of change was even negative for Hormozgan, Kordestan, Zanjan Azarbaijan gharbi,, Alborz, Gilan, and Kohkilooei and Boirahmad). This finding suggests a gradual improvement in the affecting factors in these regions. On the other hand, the results of our study revealed that the incidence of GC is rising alarmingly in the central parts of the country, suggesting a steady raise in the effect of factors affecting GC in Iran.

With regard to the geographical distribution of the type of GC, the results of the present study showed that in Iran, different types of gastric cancer are observed with a highly significant intra-country variation. For example, when compared to the other Iranian provinces, the highest and lowest percentages of A1 type of GC were reported from Zanjan and Hormozgan respectively. The reason for this discrepancy in Iran is possibly to be found in a wide range of differences in the environment-genetic interaction, ethnicity, and lifestyle (especially dietary patterns) [14].

With regard to the location of GC tumors, the results of our study revealed that cardia is the most common location of GC among Iranian patients. This observation was also reported globally as according to WHO, gastric cardia cancer was responsible for 49.5% of all GC cases [16]. The results of the present study also suggested that pillory was the most common location of GC tumor in Iranian women whereas, in men, fundi was more common. Also, our study suggested that the location of GC is more common in cardiac than the other parts of the stomach in the northern provinces, whereas pylorus is the more common location of GC in the southern part of the country. The distribution of the location of GC in men and women is significantly different suggesting a partial difference between the two genders in factors determining the location of cancer in the stomach. These findings may also help us to understand the differences in the etiology of GC between the two genders and different countries. In that regard, in a meta-analysis, Abdulrazak reported that Helicobacter pylori infection is more frequent among men than women [17]. The difference between the two genders may also indicate the involvement of hormonal differences, behavioral related factors (e.g. smoking, alcohol, and drug use), and occupational exposures. For example, it is reported that lifestyles such as physical inactivity and obesity play important roles in the risk of cardiac gastric cancer. It is also suggested that sturgeon in women may protect them against the progression of gastric cancer [11]. Accordingly, delayed menopause and increased fertility may decrease the risk of gastric cancer among females [11]. The reported differences in the regional distribution of some risk factors may explain the observed geographical differences and trends of many types of cancer [14]. In that regard, Norouzinia reported that in different parts of Iran (Khorasan, Lorestan, Tehran, East-Azarbaijan, Sistan&Balochestan, Kurdestan, Mazandaran, and Khuzestan) the majority of tumors were distal gastric. They also suggested that many factors such as environmental, lifestyle, and ethnicity in different geographical locations may contribute to the overall incidence and the anatomical location of GC [8]. For example, variation in dietary patterns and certain cooking methods including broiling of meats, roasting, grilling, sun drying, and curing may explain why the risk of GC and the distribution of its types and locations are highly vary in different regions of Iran [16, 18]. Accordingly, the upward trend in GC in the northern part of Iran could be due to particular food combination (e.g. fiber, dairy foods and meat) and preparation methods (e.g. boiling, roasting or smoked) [19].

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