This first study ever investigating BC trends in Egypt from a population-based cancer registry provided evidence of increasing BC incidence during the study period. Previously, a small-scale, hospital-based study from Alexandria, Egypt had suggested an increase in incidence rate of BC there.29
Rising BC incidence has been reported from most places in the world,1
with rapid increases observed in developing countries30
, including those in the Middle-East.31
Apart from increasing exposure to known risk factors of BC it is likely that the Gharbiah registry is relatively new and the increased BC incidence observed in our study was due to an increase in the number of diagnostic and treatment centers in Gharbiah.32
We observed three-to-four times higher incidence of BC in urban than in rural areas. The higher urban incidence was consistent across eight years and for all age groups. Although known risk factors might be responsible for the observed higher urban incidence, EDHS findings indicated that urban and rural Egyptian women had similar reproductive risk factors.28
Furthermore, when we controlled for FFTP, one of the most important reproductive risk factors affecting BC risk, the urban-rural IRR changed slightly.
We considered that the elevated BC incidence in urban areas relative to rural areas could be due to limited access to diagnostic facilities in rural areas, possibly causing many rural women to die with BC undiagnosed. However, we did not find any significant difference in stage distribution of BC between urban and rural areas () which ruled out late detection of cases from rural areas. Primary healthcare coverage in Egypt is reported to be 100%, with rural areas possibly having good access to physicians and primary care hospitals.22
Also, rural areas in Gharbiah are no further than 50 kilometers from Tanta, the capital city, and are mostly well-connected by readily available, inexpensive public transportation. Thus, difficulties in health care access and non-detection of cases cannot explain urban-rural or district-level differences reported in this study. EDHS results28
and our recent follow-up study (unpublished data) indicate that health seeking behavior of women in northern Egypt does not differ significantly between urban and rural areas. As such, health education programs related to breast health awareness must be incorporated equally in both urban and rural areas.
Distribution of the proportion of breast cancer cases by AJCC stage in Gharbiah, Egypt from 1999–2006
Urban- rural differences in BC incidence in Egypt and other developing countries are qualitatively analogous to the pattern of differences in incidence reported between developed and developing countries. This analogy is consistent with the patterns seen in age-specific BC incidence, where urban age-specific BC incidence is higher for all ages with patterns similar to developed countries. In contrast, the lower incidence in rural areas in this study showed a decrease in incidence in later years of life, similar to that seen in developing countries.30
We pose that the absence of a decline in incidence in older women in developed countries and urban areas could be due to sustained increased exposure to estrogenic factors throughout the lifetime. The increasing peak age of BC incidence that we observed is consistent with the above explanation since chronic estrogenic exposures throughout life increases BC incidence in later years of life.
We also observed an apparent decrease in urban BC incidence while rural BC incidence seemed to increase steadily across the study period though not significantly. The decrease in urban BC incidence occurred in the last four years (2003–2006) of our study and we believe that it is associated with 3–5% annual missing cases in these years since the data for these years wasn’t completely available at the time of our analysis. According to our assessment of the source of these cases, almost all of these cases were urban. The steady increase in rural BC incidence is consistent with our hypothesis since rural women are increasingly adopting urban lifestyles, reproductive habits and are also increasingly exposed to similar environmental factors as urban women due to economic development. Thus, it is quite probable that the urban-rural gap in BC incidence will become narrower in the coming decades.
BC incidence between the different Gharbiah districts also varied by as much as three-folds. Since the geographic distance between an incident case’s dwelling and the registry does not appear to affect the probability that the case will be detected and, by the procedures in place to track records, it does not affect the registration, we propose that perhaps exposures related to the relative economic development and industrialization between the districts are more relevant in causing these inter-district differences. Tanta and El-Mehalla, are the largest cities and are home to most of the industries and commercial centers of the province. Therefore, we speculate that women in these two districts may experience greater exposure to environmental risk factors such as xenoestrogens, a hypothesis that needs further investigation.
Although the link between xenoestrogens and BC has not been thoroughly explored, the evidence available suggests that exposure to xenoestrogens is high and increasing across the world. World pesticides sales have increased most in developing countries, and are two to three times higher than the current world average.33
Of further concern is exposures to plastics, which contain BPA and phthalates, is increasing in urban areas.34
These compounds are being detected in the urine of people in developed countries, 35–38
universally across the population. This can probably be ascribed to massive increases in plastic usage worldwide.39, 40
Short-acting xenoestrogens are also seen in other categories of products, such as food preservatives, cosmetics, and detergents.41–43
Recently, many studies have shown the greater presence and exposure to xenoestrogens in urban areas across many parts of the world.9–17
In our own work in Egypt, we previously discovered that urban women had higher levels of 7,8-dihydro-8-oxo-2’-deosyguanine (8-oxo-dG),44
suggesting greater exposure to carcinogenic influences. Within Gharbiah province, studies have shown dangerously high levels of heavy metals and inorganic pollutants in the Damietta branch of Nile River that flows along the east border of the province.45
There is also additional evidence of sewage and industrial wastewater polluting the Nile River mostly in the urban areas of Gharbiah province.46, 47
Thus, in addition to xenoestrogens, carcinogenic exposures in urban areas might also involve other endocrine-disruptors and genotoxic substances. Further research is clearly warranted about these environmental risk factors in Egypt and other developing countries.
One of the biggest strengths of this study derives from the fact that we saw a consistent pattern across eight years between urban-rural populations, in all age categories and districts, based on data from a population registry. However, this study also had a few limitations. As mentioned earlier, we had 3–5% of cases were missing for the years 2003–2006 and we determined that most of these missing cases were urban (results not shown). This could have resulted in a seeming reduction in the urban BC incidence and a consequent underestimation of the urban-rural IRR for the years 2003–2006. Also, the absence of information on individual risk factors as well as environmental exposures related to BC is a limitation. However, such information is not usually a part of the data collected by cancer registries, so this limitation is not particular to our study.
To our knowledge, no previous studies in developing countries have yet shown such a stark contrast in BC incidence between urban and rural populations. Future studies investigating the association of environmental risk factors such as xenoestrogens and BC at the individual level must consider that urban-rural populations in developing countries provide an ideal setting in terms of contrasting populations to analyze such exposures.