Cancer patterns in Iran: a gender-specific spatial modelling of cancer incidence during 2014–2017

Cancer is a complex and multifaceted disease that continues to be a critical global public health concern. Despite significant advances in cancer research and treatment, the lack of a universal preventative approach remains a significant challenge. The impact of cancer on individuals, families, and communities worldwide cannot be overstated, as it causes high levels of morbidity and mortality [1]. The burden of cancer is not limited to developed countries alone, but it also affects low- and middle-income countries, where resources for prevention, early detection, and treatment are often scarce. Approximately 70% of all cancer cases occur in low- and middle-income countries [2, 3]. It is predicted that the number of cancer cases in low- and middle-income countries will increase five-fold by 2030 [4]. In recent decades, developing countries have faced a growing challenge in providing equal access to healthcare services and managing the resources, Iran is no exception to this trend [5]. More than 50,000 new cases are diagnosed in the Iranian population each year [6]. Cancer poses a major health concern in Iran, as it is the second most prevalent chronic non-communicable disease and the third leading cause of death. There has been an increase in the number of new cases of cancer in recent years, highlighting the growing burden on the nation [7].

The environment has a direct impact on people's health, including the occurrence of cancer. Cancer patterns differ among populations and regions, primarily due to environmental factors such as industry environments [8], climate [9], socioeconomic status [10], access to healthcare [11], as well as physical activity [12], family history [13], age [14], and sex [15]. These factors collectively contribute to variations in cancer incidence rates and overall health outcomes. Studying cancer incidence patterns in specific areas can help identify clusters of high rates, revealing hypotheses about the link between environmental risk factors and localized cancer occurrences.

Early diagnosis of cancer can significantly reduce mortality rates. However, the high cost of screening procedures often makes it difficult for health systems, particularly in developing countries, to screen all individuals and detect cancer at an early stage [16]. Therefore, identifying high-risk areas is crucial for effective cancer screening and control policies. Spatial analysis, like the use of spatial scan statistics (SaTScan) and spatial autocorrelation, helps identify disease clusters and patterns. These methods are used to identify spatial clusters of disease incidence in geographic regions and offer valuable insights to guide policymakers in developing targeted interventions and improving public health [17, 18].

Many studies in Iran have conducted spatial analyses, typically focusing on the province scale or specific types of cancer. Kiani et al. have explored the geospatial patterns and analyzing data on cancer occurrence in Khorasan-Razavi Province [19]. Meanwhile, Babaee et al. examined geo-epidemiological of the most prevalent cancers at the provincial level in Iran in 2014 [20]. In a prior investigation, spatiotemporal patterns of gastric cancer incidence in Zanjan Province were examined. The findings indicate significant variations in the spatial distribution of gastric cancer incidence in the study area [21]. An additional investigation sought to examine the incidence patterns of high-risk clusters of breast and prostate cancers in Kerman Province between 2014 and 2017. The study observed a noticeably higher incidence rate in the northwestern region of Kerman, which could be used to develop customized screening and surveillance systems [22]. Another study utilized a spatial analysis to investigate the spatio-temporal distribution of colorectal cancer in the Iranian military community from 2007 to 2016 [23]. The study highlights the north and northwest regions of Iran as high-risk areas for this cancer, which should be considered in designing disease prevention [23].

To our knowledge, there is a lack of a comprehensive analysis of cancer incidence at the county level in the whole country. Cancer occurrence patterns vary widely across different geographic regions, and analyzing these patterns at the county level can offer valuable insights into the high-risk patterns. By identifying high-risk areas, public health officials can prioritize their efforts and allocate resources more effectively to prevent cancer and improve outcomes for affected individuals. To address this gap, we conducted a study to analyze the spatial patterns of top cancer incidence in Iran from 2014 to 2017 at the county level, with a focus on gender differences.

We have investigated the spatial patterns of six common cancer incidence among Iranian men and women for the years 2014–2017, utilizing data from the Iranian population-based cancer registry. This study represents the first attempt to explore the spatial high and low-risk clusters of common cancers in Iran at the county level, while also accounting for gender differences. Based on the results, the number of cancer cases in men was higher than in women and the average age of cancer in women is lower than in men. The findings revealed that various types of cancer exhibited regional variations, with specific regions in Iran being identified as high-risk areas for common cancer types.

Comparing the incidence and mortality rates of cancers in 2020 in Iran reveals that the rankings differ. The position in the mortality rank does not completely overlap with that in the incidence rank. This is because the death rate is noticeably higher for certain types of malignancies compared to others [33]. Stomach, lung, and liver (including trachea and bronchus) remain the top three deadliest cancers in the general population. On the other hand, prostate and thyroid cancers have the most favorable prognosis, with a 5-year survival rate close to 100% [34]. The incidence of cancer is influenced by the rates of detection and diagnosis. If a region has efficient screening programs and accessible healthcare, they may identify and report more cancer cases, resulting in a higher incidence rate. On the other hand, lower mortality rates may be attributed to early detection and effective treatment options. Early detection of breast cancer plays a crucial role in improving patients' prognosis and reducing mortality among women [35].

A recent study by Roshandel et al., revealed that the incidence of cancer in Iran is on the rise and currently exceeds the global average [36]. Different factors can contribute to an increasing trend in cancer incidence. Stomach cancer was the most common cancer among men and the fourth most common cancer among women. Previous studies have indicated that the northwestern regions of Iran exhibit a higher prevalence of stomach cancer among both men and women. This observation was likely attributed to the presence of common risk factors shared by individuals in these areas. One such risk factor is Helicobacter pylori infection [37]. Numerous studies have demonstrated a significant prevalence of this infection in these areas [38, 39]. In Ardabil Province, the prevalence of Helicobacter pylori infection was found to be over 89% among individuals aged 40 years old and above [40]. The usage of biomass for cooking and heating in the cold climate of northwestern Iran is another contributing factor to the high incidence of stomach cancer in this region. This is due to the increased exposure of residents to polycyclic aromatic hydrocarbons, which have been identified as a risk factor for stomach cancer, according to studies [40]. Tobacco use, including cigarettes smoking, as well as a high intake of salt and red meat, low consumption of antioxidants, poor oral and dental hygiene, and opium use are all considered as risk factors for stomach cancer [41‐44]. Based on our study we have found that men are more likely to develop stomach cancer than women. One possible explanation for this is that women tend to have higher levels of estrogen hormone compared to men, and this hormone has been shown to have a protective effect against the development of stomach cancer in women [45].

Based on our results, non-melanoma skin cancer was the second common cancer among both men and women. Studies indicated that this type of cancer was more common in men than in women and was more commonly observed in older age groups and increasing incidence rates reported in Iran [46, 47]. Skin cancer is primarily caused by exposure to ultraviolet radiation [48]. People who are frequently exposed to sunlight have a higher risk of skin cancer than those who are less exposed to light [49]. Men, due to their occupations, tend to be more exposed to sunlight, resulting in a higher incidence of skin cancer among men compared to women. In our study, Isfahan and Chaharmahal and Bakhtiari Provinces had the highest incidence rates of skin cancer. Sun exposure is a major risk factor for skin cancer worldwide, and Isfahan province has a sunny and dry climate with high UV radiation levels. Lumpy skin disease (LSD) is a transmissible disease in cattle that causes skin lesions on the human body. This disease is transmitted through a virus that causes skin cancer in humans. According to a study conducted by Gehsareh Ardestani and colleagues, this disease was prevalent in Chaharmhal and Bakhtiari province, and the results of this study showed that there is a risk of contracting LSD in this province [50]. Natural background radiation is the radiation that comes from natural sources, such as cosmic rays, rocks, soil, water, and air. A study by Mortazavi et al. found that Chaharmahal and Bakhtiari province had one of the highest levels of natural background radiation in Iran, and suggested that this could increase the risk of skin cancer in the local population [51].

Prostate cancer was a prevalent cancer in men, ranking as the third most common. Smoking has been identified as the most significant cause of prostate cancer [52]. The incidence rate of prostate cancer varies geographically and this indicates the impact of environmental factors on its occurrence. For instance, arsenic compounds classified by WHO as cancer-causing agents in prostate cancer cases. There has been an increase in prostate cancer cases in Iran [53]. Therefore, promoting a healthy lifestyle and regular screening programs could potentially reduce the incidence of prostate cancer.

Bladder cancer was more commonly diagnosed in men, with its incidence being four times higher in men than women [19]. Recent studies suggest an upward trend in bladder cancer incidence rates [54]. The two primary risk factors for bladder cancer are smoking and age [54‐56], where smokers are at a four-fold increased risk of developing bladder cancer [57, 58]. Smoking is particularly prevalent in the provinces of Yazd and West Azerbaijan which also have a high incidence of bladder cancer, indicating that smoking may be linked to the higher occurrence of this disease in these region [59, 60]. Opium consumption has also been shown to increase the risk of bladder cancer, and Kerman Province is one of the areas with high opium usage and subsequent higher incidence of bladder cancer [61].

Lung cancer was a significant health concern in Iran, with it being the fifth most common cancer among men and the second most deadly cancer in many parts of the country [62]. Research shows that men are more likely to be diagnosed with lung cancer than women, which can be attributed to the higher rates of smoking among men [63, 64]. Other risk factors for lung cancer include air pollution, hookah use and opium consumption [64]. According to our study, northwestern regions of Iran have a higher incidence of lung cancer. Previous studies have shown that the West Azerbaijan province has been identified as having high rates of smoking [59].

Among women, Breast cancer was the first most common type of cancer. It has been observed that Iranian women tend to be diagnosed with this disease approximately ten years earlier than women in developed nations [65]. According to our study, Tehran, Alborz, and Mazandaran provinces have the highest incidence of breast cancer. Additionally, the provinces of Isfahan, Fars, Yazd, and Kerman also show a high incidence rate following these regions. Air pollution and higher exposure to carcinogens in urban areas might be contributing to the increased number of diagnosed breast cancer cases in these provinces. [66‐68]. Factors such as smoking, lack of physical activity, an unhealthy lifestyle, and having a body mass index over 30 are known to be associated with an increased risk of developing breast cancer [69, 70]. With the decline in fertility rates among women, it is predicted that the number of breast cancer cases will double by 2030 [71]. Isfahan has a lower marriage rate compared to other provinces, which may contribute to the high incidence of breast cancer in the region. Moreover, many women in Isfahan are unaware of breast cancer symptoms. [72]. The aforementioned findings underscore the importance of implementing awareness programs in high-risk areas to bridge the information gap and, consequently, reduce the burden of breast cancer [35].

Thyroid cancer was currently the third most common type of cancer among women. Recent studies have shown a significant rise in the incidence of thyroid cancer [36]. Based on our results, the provinces of Fars, Kerman, Yazd, Isfahan, Kohgiluyeh and Boyer Ahmad, Chaharmahal and Bakhtiari were identified as high-risk areas. Obesity is one of the known risk factors for thyroid cancer. According to a study conducted by Djalalinia et al., they examined the pattern of obesity and overweight in the country and among two groups of women and men, and in the women's group, Yazd, Kerman, Kohgiluyeh and Boyer Ahmad, Chaharmahal and Bakhtiari provinces were identified as high-risk areas [73]. Studies have shown that provinces with a higher prevalence of obesity also tend to have a higher incidence of thyroid cancer [74, 75]. A history of exposure to radiation in the head and neck area can increase the risk of thyroid cancer[76]. According to a study conducted by Dr. Shahbazi in the Chaharmahal and Bakhtiari provinces, it has been found that the presence of background radiation in this region is associated with an elevated risk of developing thyroid cancer [51].

According to our findings, the high-risk areas for BNS cancer were in the provinces of Kerman, Fars, Semnan, South Khorasan, Razavi Khorasan, Kohgiluyeh and Boyer-Ahmad, Isfahan, Chahamhal and Bakhtiari and Yazd. The cause of central nervous system malignancies is generally unknown [77]. Over the past few decades, extensive epidemiologic research has been dedicated to identifying environmental factors that contribute to the development of brain tumors. Regrettably, despite these efforts, significant advancements in this area have been limited. According to a study by Oloumi.et al. lead, cadmium, arsenic, thallium mercury increase the risk of BNS cancer [78]. Salari et al. conducted a study that provides evidence supporting the presence of lead in the soil of Kerman province. This finding can be attributed to several factors, including the existence of lead mines and industrial areas within the province [79]. Furthermore, another study focused on assessing the concentration of toxic heavy metals in the blood of residents in Kerman. This investigation aimed to determine the potential exposure levels and impacts of such metals on the local population [80]. Additionally, a study conducted in Isfahan province revealed the presence of lead and cadmium in both groundwater and soil samples within the region. This investigation shed light on the environmental contamination of these heavy metals in Isfahan province [80]. In Yazd province, the amount of lead is higher than normal [81, 82]. Other potential risk factors have been identified, including exposure to electromagnetic fields, environmental factors, occupational hazards, and long-term exposure to cigarette smoke, particularly among the spouses and children of smokers [83]. According to a study conducted by Sohrabi et al. in 2011 in the provinces of Fars, Chaharmahal, Bakhtiari, Kohgiluyeh, and Boyer Ahmad, smoking was the highest among men [84].

Comprehensive information about cancer incidence enables policymakers to make informed decisions regarding screening and treatment enhancements. Knowing where high-risk areas are located allows tailored interventions for specific populations. By prioritizing prevention, specialized care, and supportive environments, policymakers aim to enhance rehabilitation services in early detection, treatment outcomes, and the quality of life for cancer-affected individuals. Ultimately, the goal is to achieve evidence-based comprehensive information for effective policymaking.

The cancer registration office in Iran had outdated information that was reported with a delay of 3 to 4 years. The accuracy of data recording was also compromised due to the absence of accurate electronic recording, leading to errors during data entry. Another limitation was the lack of an annual census in Iran; instead, we used the results of the latest census conducted in 2016. As well, there are some limitations about Kulldroff scan statistics. This method assumes that the disease cluster shapes follow predefined geometric forms, such as circles or ellipses. However, real disease clusters can have irregular shapes, making it more difficult for the method to accurately detect them. Also, it relies on a defined maximum cluster size parameter that determines the maximum number of cases that can be considered within a cluster. Selecting an appropriate cluster size can be subjective, and different choices may lead to varying results. It's important to note that while the Kulldorff SaTScan method has limitations, it is still a widely-used and valuable tool for disease cluster detection and spatial epidemiology analysis.

The study's findings on the geospatial patterns of common cancer incidence in Iran offer valuable insights into the distribution of these diseases. Stomach, non-melanoma skin, and colon cancers were common among both women and men, and the spatial patterns in both genders were similar. By identifying high-risk areas, policymakers can more effectively design targeted screening programs that facilitate early diagnosis and disease control. Such initiatives can help reduce the burden of cancer by facilitating timely interventions and improving healthcare outcomes. This study provides a fundamental assessment that can help generate hypotheses regarding associations between risk factors and high-risk areas for future studies.