Cancer Incidence in Young People in Saudi Arabia: Relation to Socioeconomic Status and Population Mixing
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Cancer incidence in young people in Saudi Arabia: relation to socioeconomic status and population mixing Reem Saeed AlOmar Submitted in accordance with the requirements for the degree of Doctor of Philosophy The University of Leeds School of Medicine March 2015 iii The candidate confirms that the work submitted is her own and that appropriate credit has been given where reference has been made to the work of others. This copy has been supplied on the understanding that it is copyright material and that no quotation from the thesis may be published without proper acknowledgement. © 2015 The University of Leeds and Reem S. AlOmar. iv To Mummy and Daddy v Acknowledgements I am very grateful to both my supervisors Drs Graham Law and Roger Parslow for their patience and invaluable emotional and academic support throughout the past four years. Their patience was invaluable during my pregnancy and delivery of my child in the first year, as well as the continued stress in raising a child and studying full-time. I understand I was not the most straightforward student and for that I will be indebted to them forever. This PhD would not have been possible without funding from the University of Dammam. I acknowledge the head of the Family and Community Medicine Department Dr. Sameeh Al-Almaei for his help moral support. I also acknowledge Mr Othaim Al-Othaim from the Central Department for Statistics and Information for his support in deciphering the census data. I would like to thank Engineer Zaki Farsi for his generosity in providing me with digitised maps of Saudi Arabia. I would also like to thank all my colleagues in the office, especially Marlous Van Laar, Oras Al-Abbas and Arwa Al-Thumairi for allowing me to vent some of my frustrations and for their continuous support. Finally, I would like to thank my daddy, for believing in me, supporting me and being proud of me. I thank him for the so many tearful phone calls and his continuous questions about my submission date. Thanks to mummy for her everlasting love and support, and I am very sorry for not being by your side the last five years, I promise it will not happen again. My thanks are also in order to my husband, who has kept up with my mood swings for quite some time, as well as to my brothers and sisters for their sincere love and support. To my son Saeed, I wish to apologise for not being the best mummy, but I promise I will make it up to you very soon. vi Abstract This study describes cancer incidence in under 24 year olds, particularly leukaemias, lymphomas and central nervous system tumours. It also describes the socioeconomic status (SES) of the geographically delimited Governorates in Saudi Arabia, by deriving two indices – the first time this has been done in the country. It also sought to determine whether SES and Hajj (occurring in Makkah) as a measure of population mixing has an association with the incidence of these cancers. During 1994 to 2008, 17,150 cases were identified from the Saudi Cancer Registry. Census data were accessed for 2004 and included 29 indicators. A continuous SES index was constructed using exploratory factor analysis (EFA) and a categorical index using latent class analysis (LCA). Incidence rate ratios (IRRs) were calculated for cancers in Makkah compared to other Governorates by year to assess the effect of Hajj, and for all Governorates to assess the effect of SES. The Hajj had no significant effect on the incidence for all cancer groups. The continuous index produced by EFA consisted of scores ranging from 100 to 0, for affluent to deprived Governorates. The LCA found a four-class model as the best model fit. Class 1 was termed ‘affluent’, Class 2 ‘upper-middle’, Class 3 ‘lower- middle’ and Class 4 ‘deprived’. The urbanised Governorates were affluent, whereas the rural Governorates were on average more deprived. For SES, an elevated risk was found for acute lymphoblastic leukaemia in the affluent class (IRR=1.38, 95%CI=1.23-1.54), and was reduced in the deprived class (IRR=0.17, 95%CI=0.10- 0.29). Similar associations were observed for all cancer groups. The findings are not supportive of the PM hypothesis, but give support to the delayed infection hypothesis, suggesting that delayed exposure to infections may prevent immune system modulation, although results may be exacerbated by poor case-ascertainment/under-diagnosis in deprived areas. Similarities between the two indices suggest validity. vii Table of Contents Acknowledgements ..........................................................................................................v Abstract ........................................................................................................................... vi Table of Contents .......................................................................................................... vii List of Tables ................................................................................................................... xi List of Figures ............................................................................................................... xiii List of Abbreviations .................................................................................................... xvi List of Equations ........................................................................................................... xix 1 Introduction ..................................................................................................................1 1.1 Study rationale ........................................................................................................1 1.1.1 Infectious hypotheses ..........................................................................................2 1.2 Aims and structure of the thesis ...........................................................................5 2 Literature review ..........................................................................................................6 2.1 Cancer ......................................................................................................................6 2.1.1 Haematopoietic cancers ......................................................................................6 2.2 International variations in cancer incidence ..................................................... 10 2.2.1 Childhood and young adult cancers ................................................................. 11 2.3 The Saudi Arabian context .................................................................................. 15 2.3.1 Cancer incidence in Saudi Arabia .................................................................... 15 2.3.2 Childhood cancer incidence in Saudi Arabia.................................................... 16 2.4 Cancer aetiology in children and young adults ................................................ 17 2.4.1 Genetic predisposition and susceptibility ......................................................... 17 2.4.2 Environmental and lifestyle factors .................................................................. 17 2.4.3 Infections .......................................................................................................... 21 2.5 Socioeconomic status ......................................................................................... 50 2.5.1 Socioeconomic status and health .................................................................... 51 2.5.2 Socioeconomic status and childhood cancers ................................................. 52 2.5.3 Socioeconomic trends and patterns ................................................................. 52 2.5.4 Measures of socioeconomic status .................................................................. 53 2.5.5 Socioeconomic status in Saudi Arabia ............................................................. 58 2.6 Research to be conducted .................................................................................. 60 3 Materials and analytical methods ............................................................................ 61 3.1 Administrative geography ................................................................................... 61 3.2 Data sources, collection and manipulation ....................................................... 63 3.2.1 Cancer data ...................................................................................................... 63 viii 3.2.2 Census data ..................................................................................................... 64 3.2.3 Hajj data ........................................................................................................... 67 3.2.4 Geographical information systems ................................................................... 69 3.3 Descriptive analytical methods .......................................................................... 69 3.3.1 Descriptive statistics ......................................................................................... 69 3.3.2 Standardised incidence rates ........................................................................... 69 3.3.3 Cartography ...................................................................................................... 71 3.3.4 Funnel plots ...................................................................................................... 73 3.3.5 Case ascertainment ......................................................................................... 73 3.4 Derivation of area-based