The main aim of this study was to explore the spatio-temporal patterns of the incidence of breast and prostate cancer at a high-resolution geography scale. To the best of our knowledge, this is the first study to assess spatial variations in the incidence pattern of breast and prostate cancers in Iran. The study area in the South of Iran revealed a high incidence rate of both cancers in north-western Kerman, while it was low in the south-eastern part of the province. The number of people with breast or prostate cancer increased considerably after patients reached 25 and 45 years of age, respectively. Further investigations are needed to assess the drivers in the high-risk areas identified in north-western Kerman. They might be associated with environmental factors and lifestyles (12), poor access to cancer-specific services (29), hereditary reasons (10) and/or socio-economic inequalities (30, 31).
Environmental risk factors such as air pollution (32-34) and presence of heavy metals (35, 36) could be linked to the geographic outcome disparities for both cancer forms. We found high-risk areas for the whole study period of breast and prostate cancers in the north-western part of Kerman, an area extending southeast of the Iranian volcano-plutonic copper belt (37) where arsenic contamination is one of the most significant environmental concerns (38). This is the location of the Sarcheshmeh copper industrial plant, the biggest copper mine of Iran, and it is likely that the neighbourhood is contaminated also by other heavy metals. Field studies report widely distributed travertine rocks north of the Sarcheshmeh copper mine indicating the presence of a highly concentrated range of arsenic compounds (38), which could seep into the water system and contaminate the drinking water in nearby urban and rural communities (38, 39). Indeed, the arsenic concentration in the water in these areas is higher than the limit recommended by the World Health Organisation (WHO) for drinking water (38, 40, 41). Arsenic has been categorised as a Group 1 carcinogen factor by the International Agency for Research on Cancer (IARC) (42) and various studies associate arsenic and breast cancer (43-46); its presence in the study area is thus a potential explanation for the increased incidence of breast cancer found. However, it should also be mentioned that other studies do not show any significant association between breast cancer and arsenic (47, 48). However, it is conceivable that he power of this association can change due to local and individual diversities (45).
Previous studies indicate a significant association between arsenic-enriched water and prostate cancer incidence (46, 49, 50), while increased levels of copper has been linked with the initiation of prostate cancer (35). Copper smelting and toxic discharges have led to soil pollution, especially in the region of the smelting plant in Sarcheshmeh Copper Complex. Importantly, the most contaminated areas are located in the most common wind directions (51), and it is particularly disturbing that the polluted areas are also used as grazing land enabling toxic elements from this soil to enter the food chain. These elements include various heavy metals in addition to copper and arsenic, e.g., lead, molybdenum and cadmium (51). Therefore, soil, water and nutrition of Rafsanjan and the adjacent townships, located in the north-western part of the province are subject to these potential negative effects. Indeed, previous studies have found associations between heavy metals and both breast and prostate cancers (52-54). The current study strongly recommends examining the hypothesis that exposure to heavy metals, especially arsenic and copper, may be associated with high incidence of gender-specific cancers. In fact, the high incidence of both breast and prostate cancers in north-western Kerman may be associated with these contaminants and this need to be investigated in future studies
Air pollution, such as that due to particulate matter, has been shown to be associated with breast cancer (33, 34). Further studies are suggested to confirm the effects of airborne pollution on the risk of breast cancer, especially particulate matter. Fazzo et al. (2016) used a spatial approach to estimate the industrial air pollution impact on 17 selected neoplasms in the territory around the industrial Sicilian area of Priolo, Italy. This area has been defined as a contaminated site of national priority for remediation because of diffuse environmental contamination caused by large industrial settlements, and their study found a higher incidence of breast cancer in the contaminated area compared to the rest of the province (55).
Previous studies highlight that poor access to health care services, such as increased incidence of cancer (29, 56), lead to poor health outcomes (57, 58). The high incidence of gender-specific cancers in some regions of the study area may be due to their considerable distance from the provincial capital with limited cancer screening programmes. On the other hand, parts of the study area in the South had the lowest incidence of both cancers investigated here although those affected were located even further away from the provincial capital. However, proximity to health care services does not directly translate into access because of potential factors such as poor socio-economic status and low level of education that also are associated with poor access (57). GIS enable researchers to assess the revealed access to cancer services through combing spatial and non-spatial factors (58-60) and the results suggest measuring access to cancer prevention programmes should be the first step when examining this hypothesis. Previous studies have highlighted the impact of the socio-economic status on the differences in the incidence of cancers of the breast and prostate (61-63). Assessing the impact of socio-economic status on the geographic disparities of the gender-specific cancers incidence in the study area can be done by analysing the overall spatial structure or identifying high-risk areas. This also warrants further studies.
Hereditary cancer syndromes, a type of inherited disorder in which there is a higher-than-normal risk of certain types of cancer, are caused by mutations in certain genes passed from parents to children (64-68). Certain such family-related cancers are well-known, e.g., hereditary breast cancer (67) and Lynch syndrome, which is a hereditary non-polyposis colorectal cancer (65). Hereditary cancer screening programmes (69-71) have made it possible to detect many of the approximately 5–10% of breast cancers caused by a genetic predisposition (72, 73) thus making it possible to prevent them before they occur. There are also studies assessing the risk of prostate cancer associated with hereditary cancer syndromes. This highlights the risk of prostate cancer in members of families associated with early-onset diseases of various kinds (68). We strongly recommend researchers and policymakers to perform hereditary cancer screening and genetic testing in areas of the province with a high incidence rate of cancer of either breast or prostate.
Spatio-temporal cluster analysis plays a significant role in visualising and quantifying geographical variation in patterns of disease incidence. Global Moran’s I and Getis-Ord General G statistic are both global cluster methods which can be used to investigate the level of spatial autocorrelation of disease patterns, while Local Moran’s I and Getis-Ord Gi* are indicate the location of the clusters. Although Getis-Ord Gi* statistic is used for identifying hotspots and the opposite, Local Moran's I is also effective for assessing statistically significant spatial outliers (74) and has therefore been predominantly applied (28, 75) and successfully assessed the hotspots (76, 77). Those using these methods for analysis of the spatial pattern of incident data should consider aggregating the incident data into polygons. The main question here is the geographical scale that should be used for aggregation because it could affect the results. In this study, we conducted the analyses both at the county and the district level, which are geographical scales providing practically useful information. We recommend other researchers performing cohort studies examining the hypotheses proposed here.
Limitations and future course of the study:
We included all patients with breast and prostate cancer in the province of Kerman during 2014-2017. However, we did not have the migration data and used the current address of patients at the time of cancer diagnosis as the patients’ residence. However, some patients might have lived in other regions in the years that might have affected their health.