Cancer incidence in the East Azerbaijan province of Iran in 2015–2016: results of a population-based cancer registry

Cancer is a major cause of mortality and morbidity worldwide. According to the GLOBOCAN project, there were an estimated 14.1 million new cases and 8.2 million deaths from cancer globally in 2012 [1]. In 2013, the cancer incidence increased to 14.9 million new cancer cases [2]. Programs for population-based cancer registration are considered the gold standard method for collecting data on all new cancer cases. Moreover, these programs are essential for estimating the burden of cancer in specific populations, particularly when seeking to provide a framework for clarifying community-based risk factors and monitoring efforts to control cancer [2–4]. A National Pathology-based Cancer Registry Program was started in Iran in 2001 and was subsequently rolled out to all provinces, including the East Azerbaijan province [5]. However, there were large differences in the coverage of cancer registry program in all state and provinces of Iran, which made this program cover about 60-70% of all cancer cases data. [5–9] Etemadi et al. has described the numerous attempts to establish a population-based cancer registry in Iran [9, 10]. One registry was maintained in the Golestan province [11–13], and its most recent results were published in the International Agency for Research on Cancer (IARC) monograph, “Cancer in Five Continents,” in 2013 [14].

The first population-based studies in Iran estimated the incidence rates of all cancer types during 1996–2000 in the Golestan, Mazandaran, and Kerman provinces [15], for the Ardabil Province for 1996–1999 [7], and for the East Azerbaijan province for 2006–2007 [16]. The Iranian national population-based cancer registration is following a five-year plan, covering 14 provinces in its first phase, and is funded by the involved universities. The East Azerbaijan Population-based Cancer Registry (EA-PBCR) was established in 2006-2007, based on the goals and responsibilities directed by the chancellor of Tabriz University of Medical Sciences. In the EA-PBCR, high rates were reported for gastric cancer (ASR 37.6 per 100,000) and esophageal cancer (ASR 24.1 per 100,000) in men, and high rates were reported for breast cancer (ASR 23.5 per 100,000) in women [16]. Stomach cancer was the most common cancer in the north and northwest of Iran [17], as well as in the Ardabil Province for both men and women, and this region has since been considered a high-risk region for stomach cancer [18]. Indeed, according to Marzban et al., death from stomach cancer is up to six-fold higher in this region compared with southern Iran [7, 19].

In this study, we aimed to establish a standard population-based cancer registry in the East Azerbaijan province. The component aims were to create the necessary infrastructures, to initiate networking and collaborations between data sources, and to estimate the incidence rates for different cancers in this province. Research grants were obtained for stable funding, and we ensured proper governance and agreement among stakeholders. In this paper, we report the first results of the EA-PBCR.

The EA-PBCR has followed international standards for data collection and reporting since its inception. For example, we linked available data from different sources to improve the validity and completeness of our results. Indeed, the MV rate, the DCO%, and the M/I ratio were comparable to those reported for middle-income countries [29–32]. Another advantage was that we created a unique NID number as a mandatory item for use by hospitals, cause of death registries, and most laboratories. This number allows for deterministic data linkage and for improvements in data validity and completeness. However, the EA-PBCR is still in its infancy, and we faced some important limitations. The DCO%, for example, was still high and was difficult to decrease in the first year. Also NID was not available for all databases, and we will try to improve this in our next reports.

We believe that the quality indicators will improve rapidly as we move forward. To improve the quality of the data produced from these sources, we have called for greater collaboration with the cause of death registry and with hospital managers.

According to this study, gastric cancer—which is the fourth most common cancer worldwide—was the most common cancer among males (ASR 29.7 per 100,000) and the third most common cancer among females (ASR 13.3 per 100,000). A few studies of the incidence of gastrointestinal cancer have been performed in the East Azerbaijan province [5, 16, 33–35]. In the most recent survey of gastrointestinal cancer in this province between 2007 and 2011, the ASR for gastric cancer was raised in both men (26 per 100,000) and women (11.6 per 100,000), and it was the second-leading cause of death (10.4% of all deaths) [34]. Other research showed that stomach cancer has been the most common cancer in north and northwestern Iran over the past 30 years [17, 18, 36]. The highest ASRs for stomach cancer in men (51.8; 95% CI 47.8–55.8) and women (24.9; 95% CI 21.5–27.2) per 100,000 were reported for the Ardebil province in 2010 [7, 18, 37]. Gastric cancer is also known to be the most common cause of cancer-related death in the country, although there is a reported six-fold geographic variation in mortality rates between northwestern and southern Iran [19]. The elevated risk of stomach cancer incidence and mortality in the northwestern region has been linked to the higher prevalence of Helicobacter pylori infection [38, 39], tobacco and opium use, and dietary factors [40–45]. A well-designed case–control study in northern Iran showed a positive association between red meat consumption and the risk of gastric cancer [46].

The incidence rates of bladder cancer (ASR 17.6 per 100,000) and lung cancer (ASR 15.4 per 100,000), which are associated with tobacco smoking and opium use [47, 48], were also high in the male population. Studies in the 1980s in Southern Iran [49] and recent studies from Golestan in northwestern Iran [50] have shown that opium is a more important risk factor for bladder cancer than tobacco. Opium use is also common in East Azerbaijan (unpublished data from a Persian cohort) and may play an important role in the etiology of bladder cancer in this province.

The ASR of lung cancer was higher, based on clinical diagnosis or DCO, in the EA-PBCR than the rate reported for Iran in GLOBOCAN 2012 (i.e., 15.4 versus 10.3 per 100,000) [1]. In the Golestan population-based cancer registry, the incidence of lung cancer was also higher than the Iranian average for males (ASR = 17.5 per 100,000) [14]. Therefore, it appears that both the pathology-based registry [6, 9], and GLOBOCAN 2012 may have underestimated the true incidence of lung cancer in Iran. The ASR of lung cancer was also low among females in both Tabriz (ASR 5 per 100,000) and Golestan (ASR 5.6 per 100,000) [14]. A recent analysis of the “National Surveys of Risk Factor of Non-Communicable Diseases (STEPS)” [sic] showed that the prevalence of cigarette smoking was high in northwestern Iran, and that 23.7% of men in the East Azerbaijan province reported being smokers [51]. By comparison, the prevalence of cigarette smoking is reported to be much lower (12.4%) among men in the Bushehr province of southern Iran, where water pipe smoking is preferred; here, the prevalence of water pipe use was reportedly 10% for men and 14.8% for women [51]. Therefore, the high incidence rates for lung and bladder cancers in the East Azerbaijan province may be linked to cigarette smoking, highlighting the importance of tobacco control measures in this region. Opium use is also an emerging risk factor for both respiratory tract and lung cancers [52], with recent cohort studies from Golestan revealing the important role of opium in such cancers [53].

The incidence rates of colorectal, prostate, and breast cancer are increasing in low- and middle-income countries [54, 55], including Iran [33, 56–58]. This study showed that the incidence rates for colorectal cancer were high for both men (20.2 per 100,000) and women (16.2 per 100,000). Likewise, high incidence rates were identified for breast cancer in women (ASR 31 per 100,000) and for prostate cancer in men (ASR 17.3 per 100,000) in the East Azerbaijan province. The World Health Organization Office in the Eastern Mediterranean Region recently published a series of recommendations for early cancer detection [59], and although they did not recommend the need for organized colorectal or breast cancer screening, they did emphasize the need for early diagnosis through improvements in public awareness and management of symptomatic patients. This recommendation might be valid for now, but we need to be prepared for a more comprehensive colonoscopy and mammography screening program in the future, when the incidence rates for these cancers can be expected to increase, making screening programs the most cost-effective options. Worldwide, prostate cancer screening is not recommended because of the high false-positive rate when using the prostate-specific antigen [59].

Based on the national cancer registry results in Iran, thyroid and laryngeal cancers are among the most common cancers of the head and neck, with oral and thyroid cancers being predominant in females [60]. Our results also showed a higher incidence of thyroid cancer in females (ASR = 7.78); indeed, it was the fourth most common cancer after breast, colorectal, and stomach cancers, with an ASR that was increased compared with a previous report from East Azerbaijan [16]. Significant associations between increased thyroid cancer incidence and lifestyle risk factors, radiation exposure, smoking, and obesity have been reported in a few studies [61–63]. The difference in the pattern of thyroid cancer incidence in our female cohort demands more comprehensive studies, which we have already started. The results of these will be presented soon.

Esophageal cancer may be one of the least common cancers in most countries, but it is the fourth most common cancer in Iran, being the second-leading cause of cancer and cancer-related mortality. The highest incidence rates have been reported for northern provinces [13]. According to the most recent results of studies in this region, there was a significant decrease in the incidence of esophageal cancer [34, 64]. However, we still observed a high incidence of esophageal cancer, especially in females, which was the fifth most common cancer among women. Compared with previous reports from the cancer registry, the ASR for esophageal cancer has shown a decrease in East Azerbaijan over the last decade [16, 34].

Finally, we found that the incidence of gynecological cancers, including ovarian (ASR 4.8 per 100,000), cervical (ASR 1.58 per 100,000), and endometrial (ASR 2.8 per 100,000) cancers, were low in East Azerbaijan. The extremely low incidence of cervical cancer was comparable to that previously reported for the Ardabil Province [7]. The prevalence of human papillomavirus (HPV) infection in women has been reported at 6.1% in the East Azerbaijan province [65], compared with 7% in Iran in general [66]. This comparatively low prevalence may be attributable to the local Muslim culture, in which more people engage in safer sexual behaviors and fewer people have multiple sexual partners [16, 66–68]. Given the low incidence of cervical cancer, neither a cervical screening program nor a HPV vaccination program would be cost-effective in this area. However, sexual behavior is changing in younger generations, and this may lead to an increase in the rate of HPV infection and the risk of cervical cancer in the future. Therefore, regular monitoring of the incidence of HPV infection and cervical cancer is warranted [69].

In this study, we presented the most current and reliable data for cancer incidence in northwestern Iran. The quality of the EA-PBCR is promising, and we believe that maintaining and developing this registry will establish a high-quality population-based cancer registry in the region. The results from the EA-PBCR could also be used to estimate cancer-specific incidence and mortality rates in Iran and neighboring countries, making it a potentially invaluable resource for the planning and monitoring of cancer control programs and for the delivery of reliable epidemiological research. Moving forward, our main aims will be to perform survival analyses of the most common cancers in East Azerbaijan, to ensure that the registry continues to exist, and to further develop the follow-up system.