Cancer Incidence in Jordan from 1996 to 2009-A Comprehensive Study

Cancer is a major public health problem, being the second cause of death in less developed countries. An estimated 7.6 million cancer deaths occurred in 2008 with 63% of the deaths occurring in less developed regions in the world (Ferlay et al., 2008). The burden of cancer is increasing in such countries as a result of the rapid growth in these populations, poverty, cancer-related infections as well as the adoption of cancer-associated lifestyle choices including; the increase in tobacco consumption, lack of physical activity and westernization of diet (Parkin, 2001; Parkin et al., 2001) Accurate statistics on cancer occurrence and outcome are essential not only to identify the causes of cancer but also for the development, implementation and evaluation of cancer control programs (WHO, 2002; Parkin, 2006). It is also important to take into account assessment of the future national financial burden caused by the increasing trends of cancer incidence. According to the WHO world health statistics report 2012, the estimated annual cancer deaths will increase from 7.6 million in 2008 to 13 million in 2030 (World Health Statistics Report, 2012). In Jordan, cancer is the second leading cause of death


Introduction
Cancer is a major public health problem, being the second cause of death in less developed countries. An estimated 7.6 million cancer deaths occurred in 2008 with 63% of the deaths occurring in less developed regions in the world (Ferlay et al., 2008). The burden of cancer is increasing in such countries as a result of the rapid growth in these populations, poverty, cancer-related infections as well as the adoption of cancer-associated lifestyle choices including; the increase in tobacco consumption, lack of physical activity and westernization of diet (Parkin, 2001;Parkin et al., 2001) Accurate statistics on cancer occurrence and outcome are essential not only to identify the causes of cancer but also for the development, implementation and evaluation of cancer control programs (WHO, 2002;Parkin, 2006). It is also important to take into account assessment of the future national financial burden caused by the increasing trends of cancer incidence. According to the WHO world health statistics report 2012, the estimated annual cancer deaths will increase from 7.6 million in 2008 to 13 million in 2030 (World Health Statistics Report, 2012).
In Jordan, cancer is the second leading cause of death university hospitals as well as clinics and laboratories throughout the kingdom. All malignant and in-situ cases diagnosed since January 1996 were registered nationwide. Jordan cancer registry uses a combination of active and passive methods in data collection performed by trained registry staff. The active method involves data collection and abstraction through regular visits to all hospitals distributed all over the country. Passive collection involves abstraction of cancer data from patients' files and completion of a standard format. CanReg4.31 was used for data entry and duplicate entry checking (CanReg4 manual. Lyon, 2001).

Population and its age composition
The population of Jordan was estimated to be 5,980,000 in the year 2009. The population is young; 48.3% were aged less than 20 years of age, and only 5.2% were aged over 60 years. Also, 51.5% of the total population is male and 48.5% female.
The Department of Statistics (DOS) in Jordan provides mid-year age composition arranged by gender and governorate. The proportional age distribution of Jordan population for each year between 1996 and 2009 was provided by DOS.

Cancer classification and rate standardization
All cases are coded according to the International Classification of Diseases for Oncology 3 th edition (ICDO-3) and the International Classification of Diseases, 10th revision (ICD-10) in the cancer registry (Fritz, 2000). Trends of incidence rates were analyzed during three periods (1996-2000, 2001-2005, and 2006-2009). Age standardized incidence rates (ASR) were calculated by the direct method, using the world standard population (Curado et al., 2007). Rates were expressed per 100,000 person-years (Chen et al., 2006).

Quality Index and analysis
Registration validity and completeness were evaluated using registrations that are considered microscopically verified (MV%) where diagnosis is based on cytological, histological or hematological reports and registrations from information on death certificates (DCO%) (Parkin et al., 1994) The data used in this article may not exactly correspond to those published in the same period of the article Cancer Incidence in Jordan, 1996(Al-Tarawnehet al., 2010, because of subsequent additions or corrections in the dataset. Student-t test was used to find the significance of difference between mean values of two continuous variables. In describing the change in trend, the terms "increase" and "decrease" were used when the rates were statistically significant (p value<0.05), otherwise the term "stable" was used.

Quality of cancer data
A total of 51,626 cases were registered during the 14-   year period. Almost all the cases (99.3%) were verified by histological, cytological or hematological examination (MV). The MV% was lower than average for cancers of the prostate, lung and cancers of eye, brain and the central nervous system (CNS). There were only 11 DCO cases for all sites combined (0.03%) as shown in (Table 1).
The crude rate (CR) for all cancer sites during the whole 14-year period was 68.6 per 100,000 (ASR: 123.6) in men. The highest CR for males was 75.5 in 2008 ( Figure  1A). For males, the top 10 sites were (in order) cancers of the bronchus and lung, colorectal, bladder, leukemia, prostate, malignant neoplasms of skin, non-Hodgkin's lymphoma (NHL), cancers of eye, brain and CNS, stomach and Hodgkin's lymphoma (Table 2).  While in women, the CR for all sites was 73.7 (ASR: 122.0). The highest CR in females was 87.0 in 2009 ( Figure 1B). The top 10 sites for women were cancers of the breast, colorectal, leukemia, thyroid, NHL, malignant of skin, cancers of eye, brain and CNS, ovary, Hodgkin's lymphoma and corpus uteri (Table 3). Figure 3 shows the CR by governorate. The highest CR was in Amman; the capital, at 109.2 per 100,000 followed by Irbid (56.7). While the lowest CR was in Aqaba (28.2) followed by Mafraq (29.3). When analyzed by region, the center had the highest CR at 85.6 per 100,000 followed by the north (48.9) and then the south (35.8) ( Figure 2B).
The incidence rates increased throughout the study period (PC: 10.8%). In males, the CR showed no significant increase by 6.8% (PC). For females, the CR increased significantly by 14.8%. The rates for the major sites, by time period, are shown in (Tables 2 and 3  stable at a (PC) of 16.6%, while colorectal cancer has shown a markedly increasing trend (PC: 97.4%). Bladder cancer, which was in third position in men, has shown significant decline in incidence (ASR: 11.4)   .2013.14.6.3527 Cancer Incidence in Jordan, 1996 with a PC of -23.2%. Prostate cancer was the fourth amongst male cancers, with an ASR of 10.2 per 100,000, with no significant change in incidence rates during the observation period (PC: 24.1%). Also, malignant neoplasms of skin (ASR: 7.9) ranked fifth throughout the whole 14-year period, with no significant changes in trend (PC: 12.2%).

Figure 5. Time Trends in Age-Specific Rates of Some Leading Sites of Cancer for A) Females and B) Males in Jordan by Period (1996-2009)
Leukemia which was ranked sixth on the scale of most common cancers in men (ASR: 7.2) declined significantly over the 14-year period (PC: -13.6%). NHL (ASR: 6.6) remained seventh throughout the observation period. It remained stable with a PC of -9.0%.
There was significant decreasing trends for stomach, cancers of eye, brain and CNS tumors and Hodgkin's lymphoma, which have remained the eighth, ninth and tenth principal malignancies in men. The PC was -19.3%, -12.4% and -15.7% respectively.
Breast cancer has remained the most common cancer in females during the 14-year period (ASR: 40.9). The incidence increased markedly at a PC of 45.2%. Colorectal cancer (ASR: 12.2) has ranked second after breast cancer exhibiting a significant increase with a PC of 60.0%.
Malignant neoplasms of skin and NHL ranked as the third and fourth most frequent cancers in females with ASR 6.0 and 5.6 per 100,000 respectively. They remained stable in the observation period (PC: -19.8%, -4.6% respectively).
Only cancers of eye, brain and CNS, which was the ninth in position among women showed significant decrease over the whole 14-year period (ASR: 3.4, PC: -31.1%). Figure 4 show time trends for all cancers combined, in males and females, by age group. Cancer incidence in the age group 15-35 has decreased in both sexes. The age groups 45-54 and 55-64, incidence has decreased for males only, while remaining stable in females. Incidence rates have tended to increase in those over 65 in both males and females. The cancer incidence in childhood (under age 15) has tended to decrease in both sexes. Figure 5 show age-specific incidence rates of the leading sites of cancer. Colorectal cancer has shown a steady increase above the age of 35 for males throughout the whole period. Notable increase has taken place in the incidence of leukemia in males over 65 and increasing trends in the incidence of breast cancer are significant mainly for women aged 45-64.

Discussion
A total of 12.6% of worldwide deaths are caused by cancer, which is more than the percentage of deaths caused by HIV/AIDS, tuberculosis and malaria put together(World Health Organization (WHO), International Union against Cancer (UICC). Global action against cancer (Geneva, 2003). Cancer is usually considered a disease of the industrialized countries, whereas infectious diseases constitute the major burden in less developed countries. However, the increase in life expectancy in the less developed countries and the rapid changes in lifestyle (Parkin, 2001;Parkin et al., 2001), have led to an epidemic of cancer in the less developed countries. With current trends it is estimated that by the year 2020, around 70% of cancer deaths will be in less developed countries (Sener and Grey, 2005).
In Jordan, health care services are well developed, and they go side by side with established national programs on disease control, health promotion campaigns and health education. Child mortality and morbidity from certain infectious diseases have decreased significantly to levels comparable to developed countries. Life expectancy at birth has risen from 67.7 for males and 71.1 for females in 1996 to 71.8 and 74.7, respectively, by Ministry of Health, Jordan (2009).
The level of MV cases (99.3%) is an indicator of the validity of diagnosis (Parkin et al, 1994;Curado et al, 2007). The pathology departments in Jordan work according to the updated revised World Health Organization (WHO) International Histological Classification of Tumors. Also, the diagnostic procedures, equipment and skills are fully adequate. There were only 0.03% of cases reported by DCO. This indicates that our data is highly accurate and the percentages of MV and DCO are comparable with many other cancer registries in North America and Europe (Curado et al., 2007). The MV% did not change significantly from 1996-2002 to 2003-2009, the MV% were 99.0% and 99.5% respectively, thus trends in cancer incidence are not likely to be caused by changes in the degree of ascertainment.
According to this study, ASR per 100,000 world population for males in Jordan (123.6) were found to be rather close to the results reported in many countries in the Middle East including; Kuwait (121), Tunisia (148.3), Iraq (107.7). However, the rates were remarkably lower in Saudi Arabia and Qatar (59 and 51 respectively) and higher in Palestine (183), Egypt (162) and Bahrain (160). Comparing the results of the less developed countries to the more developed countries; the results were found to be   (Ferlay et al. 2008) remarkably higher in the more developed countries such as USA (553) and Australia (356.8) (Table 4). ASR per 100,000 world population for females in Jordan (122) was also found to be rather close to other countries in the region such as Egypt (122), Kuwait (129) and Palestine (134). The rates were lower in Saudi Arabia (58), Qatar (87) and Oman (91). Higher rates were reported in more developed countries such as USA (416.5) and Australia (276.4).
The differences in rates between a developing country like Jordan and other more developed and industrialized countries is usually attributed to the degree of modernization and changes in lifestyle including smoking, eating habits and physical activities (Popkin, 1994). Jordanian traditional diet is known to be rich in vegetables and fruits compared to the diet of more industrialized countries and to contain less fat and meat (Behavioral risk factors survey. Amman, 2005).
Breast Cancer continues to be the most important cancer in women, being responsible for 33% of all female cancers, with significant increasing trends throughout the whole 14-year period. These trends maybe related to changes in the lifestyle of Jordanian women known to increase the risk of breast cancer. Changes in diet with an increase in energy from fat and decrease in physical activity, especially among urban residents, resulting in an increase in obesity are all among the factors proven to increase the risk in breast cancer (Ajlouni et al., 1998;Shu et al., 2001;Popkin, 2004;Khader et al., 2008). The rising trends in breast cancer also seem to be related to a decline in the number of children and an increase in the age of first childbirth (Chen et al., 2006). These  (Freedman et al., 2006) US SEER (91.1) (Ries et al., 2009) England (88.l) (Stewart-Knox et al., 2009 and Lebanon (71.0) (Lakkis et al., 2010) Jordan has a much lower ASR. The variability in ASR between Jordan and other countries in the Middle East can be attributed to differences in the lifestyle and certain genetic variations (Bernstein et al., 2003;Chlebowski et al., 2005).
Colorectal cancer is the third most common cancer in men (10.0%) and the second in women (9.4%) worldwide (Curado et al., 2007). In Jordan colorectal cancer replaced lung cancer as the first most common cancer in men in the periods 2001-2005 and 2006-2009 and the second most common cancer in women. The rates of colorectal cancer increased significantly throughout the whole period which may be attributed to changes in diet and the westernization of the lifestyle (Popkin, 1994;Giovannucci, 2002). ASR in Jordan was 13.7 and 12.2 for males and females respectively. In males the trends were lower than Qatar (16.1), Kuwait (15.2) and Bahrain (14.3) but much higher than Tunisia (10.7) (Missaoui et al., 2010), United Arab of Emirates (7.1), Saudi Arabia (6.4), Oman (5.3) (Al-Hamdan et al., 2009) and Lebanon (9.0) (Adib, 2003). Almost 60% of the cases occur in the more developed regions (Curado et al., 2007). Compared to USA SEER (54.0) (Ries et al., 2009) and the United Kingdom (55.4) (Office for National Statistics, Cancer Statistics registrations: Cancer incidence and mortality in the United Kingdom, 2004Kingdom, -2006 the trends in Jordan were much lower. The rapid increase in colorectal cancer in both males and females maybe associated with the fast rate of adoption of risk behaviors including heavy alcohol consumption (Kontou et al., 2012), smoking (Botteri et al., 2008;Belbeisi et al., 2009) and high fat diets (Ajlouni et al., 1998;Larsson and Wolk, 2007). The increase in type 2 diabetes in Jordan may be associated with the increasing rates of colorectal cancer (Yang et al., 2005;. Colorectal cancer screening is cost effective irrespective of the method used (Hawk and Levin, 2005). In the USA, the increase in colorectal cancer testing has contributed to a decline in the incidence of colorectal cancer (Meissner et al., 2006, Edwards et al., 2010. In Jordan there are no screening programs, even for first degree relatives of colon cancer cases (Arafa et al., 2011).
Lung cancer ranks the third of all cancers among cases diagnosed in the period of the study with a percentage of 6.7% for both sexes and 11.2% of all male cancer cases. Lung cancer was the most common among males in the years (1996)(1997)(1998)(1999)(2000) after which it fell second to colorectal cancer in the years (2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)). On the other hand, in females, lung cancer has been fairly stable (PC: 5.7%).
The ASR of lung cancer among males in Jordan is (7.7) which is consistent with some countries in the region; UAE (9.9) (Al-Hamdan et al., 2009), Saudi Arabia (4.8) but much lower than other countries such as Lebanon (28.3) (Adib, 2003), Tunisia (34.7) (Missaoui et al., 2010). As for females the ASR in Jordan is (3.1) falling in the 13 th place among the top cancers in females. Comparing the results to that of other countries Jordan is similar to Egypt (3.7) (Freedman et al., 2006) but lower than Lebanon (11.9) (Adib, 2003), Israeli Jews (11.4), Israeli Arabs (4.8) (Freedman et al., 2006), Kuwait (6.9) and Bahrain (10.2) (Al-Hamdan et al., 2009). In the more developed countries the results were much higher for both males and females, USA (48.6 and 31.9 respectively) (Freedman et al., 2006).
The most recognizable risk factor associated with lung cancer is smoking; 54.4% of lung cancer patients are/were smokers. The notable increase of the trend of lung cancer among Jordanian females could be due to the observed increase in the number of females who smoke Narghile (Hubbly bubbly or water pipe) and the fact that cigarette smoking among females has become more socially acceptable and hence more common (Dar-Odeh and Abu-Hammad, 2011).
Bladder cancer is one of the most common cancers among men in some Middle East countries especially Egypt with an ASR of 37 per 100,000 (Jemal et al., 2011). In Egypt the main risk factor related to bladder cancer is schistosomiasis (Mostafa et al., 1999). On the other hand, in Jordan the main risk factor is cigarette smoking (D'Avanzo et al., 1990) DOI:http://dx.doi.org/10.7314/APJCP.2013.14.6.3527 Cancer Incidence in Jordan, 1996 Compared to neighboring countries Jordan has relatively low rates. Israeli Jews have one of the highest rates in the region (27.5), followed by the Cypriots (20.5) and Israeli Arabs (16.0) (Freedman et al., 2006). ASR in Jordan is higher than United Arab Emirates (5.2), Saudi Arabia (3.7), Oman (5.6), and Kuwait (7.3) but lower than Bahrain (13.4) Qatar (14.3) (Al-Hamdan et al., 2009) and United Kingdom (19.7) (Office for National Statistics, Cancer Statistics registrations: Cancer incidence and mortality in the United Kingdom, 2004Kingdom, -2006. Leukemia incidence rates were declining in males. In Jordan, ASR for males was 7.2 which is much higher than that of the Gulf Countries (4.1). Israeli Jews showed higher rates (10.5), while Egyptian men exhibited lower rates (6.0). ASR in the US was 8.8 (Freedman et al., 2006). Furthermore, in the last few years incidence trends of leukemia in the US remained stable (Xie et al., 2003).
In conclusion, this study is an inclusive report concerning cancer incidence in Jordan in a 14-year period (1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009). The Data, obtained from the Jordan cancer registry, includes information collected for 51 626 diagnosed cases of Jordanian nationality. The overall increase in the rates of cancer incidence spanning the whole study period is 10.9%. Breast cancer is the most common cancer among females throughout the period of this study showing an alarming increase in the second half of the 14-year period. Lung cancer and colorectal cancer are the most common among males over the periods of 1996-2000 and 2001-2009 respectively. Despite the availability of data on cancer cases in the Jordan cancer registry, poor documentation of mortality data caused limitations in studying the trends of mortality and the years of survival of cancer patients. Therefore, it is highly recommended that the specific documentation of such data becomes a priority. We believe that this study provides a precise description of the trends of cancer incidence in Jordan over a considerable time period, which could be a reliable source to further study the burden and the risk factors for significant changes in cancer trends. Our findings also provide reason for the development and improvement of our plans to control and prevent the cancer epidemic.