Cancer incidence in young people in Saudi Arabia

278 Pages·2015·3.42 MB·English

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 measures of socioeconomic status ........................ 75
3.4.1 Standardised index of socioeconomic status ................................................... 75
3.4.2 Classes of socioeconomic status ..................................................................... 81
3.5 Direct Acyclic Graph and regression analyses ................................................ 87
3.5.1 Direct Acyclic Graph ......................................................................................... 87
3.5.2 Poisson regression ........................................................................................... 88
3.5.3 Negative binomial regression ........................................................................... 88
4 Results: Descriptive analyses and mapping .......................................................... 90
4.1 Demographic characteristics, incident cases and incidence rates ................ 90
4.1.1 Demographics .................................................................................................. 90
4.1.2 Incident cases .................................................................................................. 91
4.1.3 Overall age-sex standardised incidence rates ................................................. 94
4.1.4 Age-sex standardised incidence rates and ratios by Governorate .................. 96
4.1.5 Annual increase in Hajj ................................................................................... 124
5 Results: Indices of socioeconomic status ........................................................... 125
5.1 Data cleaning and descriptive statistics ......................................................... 125
5.1.1 Descriptive statistics ....................................................................................... 125
5.2 Standardised index of socioeconomic status ................................................ 128
5.2.1 Data checks .................................................................................................... 128
5.2.2 Factor extraction and factor retention ............................................................ 128
5.2.3 Factor rotation ................................................................................................ 132
5.2.4 Initial index and standardised index ............................................................... 136
5.3 Classes of socioeconomic status .................................................................... 137
5.3.1 Deciding the number of classes ..................................................................... 137
5.3.2 Examining the quality of latent class membership ......................................... 139
5.3.3 Defining and labelling classes ........................................................................ 139
ix

5.3.4 Geographical mapping of both indices ........................................................... 141
5.3.5 Comparing distributions of both indices ......................................................... 143
6 Results: Regression analyses of population mixing and socioeconomic
status, sensitivity analyses and ascertainment of cases ................................... 145
6.1 Regression analyses ......................................................................................... 145
6.2 Sensitivity analyses ........................................................................................... 155
6.2.1 Socioeconomic classes .................................................................................. 155
6.2.2 The effect of the large cities ........................................................................... 157
6.3 Case ascertainment ........................................................................................... 161
6.3.1 Proportion of cases over time......................................................................... 161
6.3.2 Incidence rates by years ................................................................................ 163
6.3.3 Comparison with the US ................................................................................. 164
7 Discussion ............................................................................................................... 168
7.1 Discussion of results ......................................................................................... 168
7.2 Discussion of data sources .............................................................................. 177
7.2.1 Data from the cancer register ......................................................................... 177
7.2.2 The census data and the Hajj data ................................................................ 178
7.3 Discussion of methods ..................................................................................... 179
7.3.1 Disease classification ..................................................................................... 179
7.3.2 Geographical mapping ................................................................................... 179
7.3.3 Possible drawbacks of disease mapping ....................................................... 180
7.3.4 Exploratory factor analysis ............................................................................. 181
7.3.5 Latent class analysis ...................................................................................... 182
7.3.6 Regression analyses ...................................................................................... 184
7.4 Strengths of the study ....................................................................................... 185
7.5 Limitations of the study .................................................................................... 186
7.6 Recommendations and future work ................................................................. 188
7.7 Future planned publications ............................................................................. 189
7.8 Conclusions........................................................................................................ 190
References.................................................................................................................... 192
x

APPENDIX A Extended classification table of the International Classification
of Childhood Cancers 3rd Edition .......................................................................... 229
APPENDIX B Main classification table of the International Classification of
Childhood Cancers 3rd Edition............................................................................... 238
APPENDIX C Saudi cancer registry data abstraction form .................................... 243
APPENDIX D Example of phase 1: Converting morphology and topography
codes to ICCC-3 extended classification.............................................................. 245
APPENDIX E Example of phase 2: Converting morphology and topography
codes to ICCC-3 main classification ..................................................................... 248
APPENDIX F Discrepancies found within the total number of households
from each indicator group and the total number of households reported ....... 249
APPENDIX G Commitment letter to Farsi GeoTech Company for use of
Geographical Information System data ................................................................ 251
APPENDIX H Syntax of negative binomial regression analysis in Stata
version 13 ............................................................................................................... 252
APPENDIX I Initial and standardised index of Saudi Governorates .................... 253
APPENDIX J Modal class assignment and the final socioeconomic classes
index of the Saudi Governorates ........................................................................... 256