Patterns of Childhood Cancer Incidence in Saudi Arabia (1999-2008)

Background: Although childhood cancer is a rare disease, 100,000 children younger than 15 years of age die from cancer each year, the majority of them in developing countries. More data need to be gathered and published particularly in developing countries to better understand the scale of the problem. Aims: This study aimed to describe the patterns of childhood cancers in Saudi Arabia over a period of ten years (1999-2008). Materials and Methods: This descriptive retrospective study was based on secondary data from the Saudi Cancer Registry from 1999 to 2008. All Saudi cases (both genders), under the age of 15 years, who were diagnosed with cancer during the study period, were included in this study. Results: Childhood cancer in Saudi Arabia, in the period between 1999 and 2008, accounted for about 8% of total cancer cases. The most common encountered cancers were leukemia (34.1%), followed by lymphoma (15.2%), brain (12.4%), and kidney cancers (5.3%). The overall incidence of childhood cancers increased from 8.8 per 100,000 in 1999 to 9.8 per 100,000 in 2008. The incidence rates of cancers per 100,000 in the years 1999 and 2008 were generally higher among males, (9.4 and 11.5 in males vs. 8.3 and 8.1 in females). The highest incidence rate in the surveyed years was apparent in the birth to age 4 years group. Conclusions: Cancer is an important public health problem in Saudi Arabia and a major ascending contributor to mortality and morbidity in children. More studies are required to describe the patterns of childhood cancers and related risk factors in Saudi Arabia.


Patterns of Childhood Cancer Incidence in Saudi Arabia
Childhood cancers in the Arab Gulf region affected around 7,673 children in the period extending between 1998 and 2008; which accounted for 8.1% of total cancer cases during the same period.(GCCCP 2011) In Saudi Arabia, the Saudi Cancer Registery reported around 770 childhood cancer cases in 2008; which represented 6.5% of the total number of cancer cases in the same year.(SCR 2007) This findings showed more or less similar readings on the percentage of childhood cancer among the total population in the different Arab countries.
The male to female ratio of childhood cancer is generally favorable towards males in some developed countries such as Australia, Canada, and the UK (1.22:1, 1.14:1, and1.12:1;respectively); (Baade et al., 2010;UK 2011;Mitra et al., 2012) which is similar to what has been reported in middle eastern countries such as Egypt, Morocco, Jordan, and countries of the Arab Gulf (JCR 2008;NCRPE 2008;GCCCP 2011;Tazi et al., 2013).
According to GLOBOCAN estimation on 2012, leukemia coming in the top of cancers among children diagnosed with malignancy in the globe (Wiemels 2012;Ferlay, Soerjomataram et al., 2013).It is followed by brain and other nervous system malignancies, non-Hodgkin lymphomas, renal tumors and Hodgkin lymphomas.However the rank of each type of cancer is not constant in all countries in the world and remarkable variations in the range of top childhood cancers are clearly noticed from one country to other.(JCR 2008;Jemal et al., 2010;GCCCP, 2011;Mitra et al., 2012).
In most of Arab Countries, including KSA, there is no enough research about the patterns of childhood cancers.This study will show the trends of childhood cancer incidence reported in the Saudi national cancer registry through the period of 1999 to 2008.It will also addressed the most common childhood cancers, and rates of childhood cancers in different regions in the KSA.Findings from this study would probably help the decision makers to plan accordingly required health services.

Materials and Methods
This descriptive study has conducted using aggregated data from the Saudi Cancer Registry (SCR) in the Kingdom of Saudi Arabia.The SCR is considered as a national cancer registry in the country in Riyadh and established in 1992 under the authority of the Ministry of Health.(SCR 2007) SCR working to collect all data related to cancer registration from all the thirteen administrative regions in the kingdom which include: Riyadh, Estern region, Makkah, Madinah, Qassim, Hail, Jouf, Northen region, Tabouk, Najran, Baha, Asir, and Jezan.Therefore, it covers all the 27,136,977 million population in the country (2010); 18,707,576 of them are Saudi nationals (Information 2012/1433).
The SCR Main Office indirectly supervises the regional offices and responsible for ensuring the accuracy and quality of data collected in all regions.Quality control processes include verification of site, morphology, and staging information as well as case linkage (tumor and patient), and consolidation of data (SCR 2007).
The data anlayzed in this study were used for the period from 1999 to 2008 (10 years period).These data were underwent a serious of steps to ensure its quality.Usually, in the original sites where regional and hospital cancer registries are located, data were abstracted from patients' medical records, whom already classified as cancer cases based on their clinical diasgnosis, histopathological, and/or radiological diagnosis.Other data (variables) were also collected as related to personal identification (name, ID Number, sex, age), demographic information (address, telephone number, nationality), and tumor details (diagnosis date, primary site, histology, behavior, grade, stage, basis of diagnosis).The primary site and histology of cancers are also identified and coded according to the International Classification of Diseases for Oncology (ICD-O-3), (WHO 2000) and International Classification of Childhood Cancer Groupings (ICCC-grouping) (Steliarova-Foucher et al., 2005).All these data were entered in the computer using a program software called CanReg 4 (IACR) for data analysis and formation of incidence tables and then transformed in to SPSS program (US version 16) for the purpose of further statistical analysis.
All Saudi cancer cases between birth to 14 years of age, of both genders, lived in Saudi Arabia, were re`gistered in the SCR in the period between 1999 and 2008, were included in the study as study subjects.However, the study has to exclude any registered cases between 0-14 years of age with missing principle data, such as age, topography, or sex identification.
Data were reviewed for incompletness or missing entries.Staistical analysis included the following: proportions, age specific incidence rates, crude rates, age standrized rates, and X 2 calculated and P value of (<0.05) considered significant in this study.Age Standardization Rate (ASR), is the theoretical rate which the population whould have if it had a standard age structure (Boyle and Parkin, 1991).The crude rate for cancer is the total number of cases registered as aproportion of the total population (Boyle and Parkin, 1991).Cancer incidence rate were also calculated for specific cancers per 100,000 of the population.The incidence rates were calculated based on the mid-point population structure for Saudi population estimated for the population pyramid reported by Central Department of Statistics and Information, Ministry of planning for year 1999 and 2008 (Information 2012/1433).We used the World Standard popualtion in ASR calculation.

Ethical considerations
No need for informed consent because the used data was secondary data with no linking to patient identity.Data from the Cancer registry were received in special codes and were analyzed and published in special codes without names.The proposal of this study was approved by the research committee in the College of Public Health  .2015.16.2.431 Patterns of Childhood Cancer Incidence in Saudi Arabia (1999-2008) and Health Informatics at the King Saud Bin Abdulaziz University for Health Sciences as well as the Institutional reseach Board of the King Abdullah Research Centre in the National Guard Health Affair at the Ministry of National Guard, Riyadh, KSA.(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008) In period between 1999 and 2008, childhood cancer (<15 years) has accounted for about 8% of total cancer cases among all Saudi cancer cases, (5932/74548 cases; unpublished), as seen in Table 1.According to the distribution of the most top cancers in children based on gender, leukemia rates (34.1%)found to be almost the same in boys and girls over the period of the study.Whereas, lymphoma and brain cancer were higher among boys, (17.9% and 12.7% vs. 11.7% and 12%, respectively).Kidney cancers were higher among girls than boys (6.3% and 4.5%, respecively).
The overall incidence of childhood cancers was increased from 88 per 1,000,000 in 1999 to 98 per 1,000,000 in 2008.However, the incidence rates were higher among boys than girls in both years 1999 and 2008, (94 and 115 in boys vs. 83 and 81 in girls/1,000,000).Age group from birth till 4 years had the highest incidence rate in both 1999 and 2008 (Table 2).
Table 3, showed that the highest reported number of cancer patients were from Riyadh followed by Makkah, then Estern Region, Madinah, Asir, Qassim, Tabouk, Jazan, Hail, Jouf, Najran, Baha, and Norther Region.However Riyadh had the highest number of childhood cancers cases (leukemia, lymphoma, brain and kidney cancers), followed by Makkah except for lymphoma estern region had the second highest number of cases.

Discussion
The occurrence of cancers in Saudi children is low in comparison to other developed countries, but it's an important public health problem as its cause loss of young lives.Saudi Arabia is a young nation with 41.7% of the popualtion under the age of 15 years, which put a large number of the population at risk of childhood cancer.(SCR 2008;Al Sudairy 2010) Some of these children, constituing almost half of the popualtion, will develop cancer at some point in their lifetime before they reach 15 years of age.
Globally, each year nearly 100,000 children younger than 15 years die from cancer, and the majority of them  and Gender (1999and Gender ( -2008) ) in developing countries with low resources, as a result of lack of availability of facilities for diagnosis of cancers and access to treatment at early stage as well as unaffordable treatment (Terracini, 2011;Sullivan et al., 2013).
Recently childhood cancers have reached cure rates up to 80% (Al Sudairy 2010).The promising treatment outcomes of malignancies affecting children makes an examination of the patterns of occurence, age allocation, and geographical distribution of childhood cancers in Saudi Arabia, as presented in this study, a very important step on the childhood cancer research agenda.
In our study we found that an overall incidence of childhood cancers accounted for 8% of all cancers recorded among Saudis during period between 1999 and 2008 (unpublished).This findings shows similarities with the results reported from the GCC States on cancer incidence for the period 1998-2007(GCCCP 2011)).However, the trend of cancer incidence cases among children in KSA in the period from 1999 up to 2008 has increased from 88 per 1,000,000 to 98 per 1,000,000, respectively.
Comparison in incidence rates per 1,000,000 populations showed remarkable low rates of childhood cancer in Saudi Arabia than other developed countries.For example, childhood cancer incidence was reported with higher rates in UK (134 per 1,000,000), Germany (163 per 1,000,000) (CR 2010; GCCR 2013).Moreover, it was also reported lower than countries in the Middle east region such as Turkey (143 per 1,000,000), and Algeria (141 per 1,000,000), Egypt (138 per 1,000,000), and Iraq (120 per 1,000,000) (Ferlay, Soerjomataram et al., 2013).However, childhood cancer rate in Saudi Arabia found to be higher than the rate in some countries from South Africa and Eastern Asia (Ferlay, Soerjomataram et al., 2013).
In our study, leukemia was the top childhood cancer as it is the commonest in most industrialized and developing countries.For example many registries in Asian countries such as Indonesia, Thialand, Japan, and Pakistan have reported leukemia as the most frequernt cancer among children which was similar to our findings (Jamal et al., 2006;Sugiyama et al., 2009;Datta et al., 2010;Srina et al., 2010;Missaoui et al., 2011;Wiangnon et al., 2011;Wahidin et al., 2012).However, lymphomas were the second common cancer in our study which resembles the same picture in most developing countries as well as the GCC states (JCR 2008;NCRPE 2008;GCCCP 2011).
Our results showed that Riyadh had the highest number of childhood cancer cases followed by Makkah and Estern region this could be due to presence of tertiary hospitals and cancer centers in these regions that cancer cases reffered to these sites from other regions in country.
In the Arab countries cancer researches face many challenges as reported in the report for an Initiative to Improve Cancer Care in the Arab World these challenges include: concentration of pediatric oncology centers in major regions, lack of public awareness, weak research activities related to pediatric oncology, and lack of national databases (Jazieh, Al Khatib et al., 2010).
Saudi Arabia like other developing countries, went through an economic transition from primarily agricultural activities to more industrial development and manufacturing after the oil boom in the Arabian Gulf (Bener, Ayub et al., 2007).Similar to other developing countries, cancer incidince in KSA increased through out the years because of improvment of health care facilities, their diagnostic capacities, the development of cancer registration practices and possibly the control of commmunicable diseases (Ibrahim et al., 2008;Ferlay, et al., 2010;Jemal et al., 2010).These factors together with the population growing, ageing, adopt western lifestyles contributed to the gradual increase in cancer incidence.(Jemal et al., 2010) The rapid socieconomic changes and lifestyle modifications with an increase in population life expectancy at birth, togather with previously mentioned factors in the country, may have contributed to the documented increase in cancer incidence.(GCCCP, 2011;Terracini, 2011) This increase in the trend of childhood cancer in Saudi Arabia may be a cause of exposure to specific unknown risk factors, so there is need for more researches in the etiology and risk factors of childhood cancer in KSA.
In conclusion, this study provides valuable clues for cancer research where it shows an increament in the trend of cancer in Saudi Arabia throughout the studied years with most common cancer was leukemia and lymphoma, which was higher among boys than girls.However, more epdemiological studies are required to describe the patterns of childhood cancer and the related risk factors in the country to implement adequate cancer control and prevention programs.This type of preventive and cancer care programs should be articulated on primary health care facilities rather than teriary services and should be integrated side by side with other routinely running programs directed to control and prevention of noncommunicable diseases.