Musah, Anwar (2017) Environmental exposure to metallic soil elements and risk of cancer in the ...

355 Pages·2017·4.86 MB·English

by  Christine Middleton

Environmental exposure to metallic soil elements and
risk of cancer in the UK population, using a unique
linkage between THIN and BGS databases

Anwar Musah, MSc

Thesis submitted to the University of Nottingham for
the degree of Doctor of Philosophy

August 2016
Abstract
Background: There have been many epidemiological studies into the
influence of exposure to the most toxic elements on the risk of cancer
in the workplace, mainly due to the exposure of certain occupational
groups, or perhaps in populations near industrial sources. Toxic
elements include arsenic, copper, nickel, and uranium; and many
more of these elements have been shown to increase the risk of
several different types of cancers in these highly-exposed groups.
Many of these elements naturally exist in the soil, and the health
impact of these levels of environmental exposures on the general
population has received little attention to date possibly due to the
belief that soil concentrations of these elements are too low to cause
harm to the general population. Therefore, the long-term effect of
such chronic exposure to metals in the soil remains unclear.
Aims and objectives: The goals are to utilise a new resource known as
THIN-GBASE for conducting a series of environmental epidemiological
studies to test the hypothesis that BCC, lung and GIT cancers are
associated with high exposure to certain low-level metals in soil. We
sought to use this resource in determining which soil metals should be
tested for predicting each of the cancer outcomes.
Methods: For BCC, an ecological study was initially undertaken to
assess the overall regional variation in BCC to provide national and
contemporary breakdowns of incidence rates across the UK. The
primary exposure of interest for BCC was low-level soil arsenic, and
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we therefore quantified soil arsenic exposure levels based on the UK
national safety limits for arsenic [i.e. As-C4SLs = 35 mg/kg]. A
population-based cohort study was conducted to quantify the risks
associated between the development of BCC and increasing levels of
exposure to soil arsenic. For lung cancer, a two-stage process was
adopted: 1) data mining analysis using the correlation-based filter
selection model was used to find the restricted set of soil metals were
best predictors for lung cancer; and 2) a prospective cohort study was
use where these sets of elements were fitted together (adjusted for
confounding variables) in a multivariable Cox proportional-hazards
model to determine the risks associated between the development of
lung cancer, with increasing levels of exposure to each specific
element. For GIT cancers, a three-stage process was adopted: stages 1
and 2 used a similar methodology for the lung cancer study. In stage
3, all GIT cancers were divided into three broader outcomes i.e. upper
GIT (includes mouth & oesophagus), stomach (as standalone) and
colorectal (includes small, large, rectum and anal canal) cancers. A
multivariate competing risk survival model was adjusted for the three
different GIT cancers as competing events to identify associations
between any of the selected group of metals found in stage 1 and GIT-
specific cancers.
Results: For BCC, the findings for the ecological study show that
overall EASRs & WASRs for BCC in the UK was 98.6 and 66.9 per
100,000 person-years, respectively. It indicates a large geographical
variation in age-sex standardised incidence of BCC with the South East
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having the highest incidence of BCC (202.7/100,000 person-years),
followed by South Central (193.5/100,000 person-years) and Wales
(185.7/100,000 person-years). Incidence rates of BCC were
substantially higher in the least socioeconomically deprived groups. It
was observed that increasing levels of deprivation led to a decreased
rate of BCC (p < 0.001). In terms of age groups, the largest annual
increase was observed among those aged 30-49 years. Assessment for
soil arsenic indicated that individuals living in areas with
concentrations ≥35mg/kg significantly had an increased hazard of
developing BCC (35-70mg/kg: adjusted HR 1.08, 95% CI: 1.02-1.14;
≥70mg/kg: adjusted HR 1.17, 95% CI: 1.09-1.28). Urban residents with
the highest exposure of soil arsenic had the greatest risk of developing
BCC (≥ 70.0 mg/kg: HR 1.18, 95% CI: 1.06-1.36). For lung cancer, the
correlation-based filter selection model identified aluminium, lead
and uranium as the appropriate set of exposures for modelling lung
cancer risk. Complete adjustments of hazards model showed evidence
of an increased risk of developing lung cancer with elevated
concentrations for only soil aluminium at medium levels ranging
between 47,000-61,600mg/kg. Urban residents with the highest
exposure of soil aluminium had the greatest risk of developing lung
cancer (≥ 61,600mg/kg: HR 1.12, 95% CI: 1.04-1.22). For GIT cancers,
the correlation-based filter selection model identified seven elements
i.e. aluminium, phosphorus, zinc, uranium, calcium, manganese, and
lead, as the appropriate set of exposures for predicting GIT cancer
risk. The complete adjustment for hazards model indicated that the
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risk of developing overall GIT cancers were significantly associated
with elevated exposure levels of soil phosphorus only (873-
1,127mg/kg: HR 1.08, 95% CI: 1.02-1.14; 1,127-1,456mg/kg: HR 1.07,
95% CI: 1.01-1.13; and ≥1,145mg/kg: HR 1.07, 95% CI: 1.01-1.13).
There were no consistent relationships identified between any of the
selected groups of elements and the GIT-specific cancer outcomes
when adjusting for different GIT cancers as competing events.
Conclusion: There appears to be slight evidence of BCC, respiratory
and GIT cancer risk with elevated exposure to soil arsenic, aluminium
and phosphorus, respectively. The series of investigations conducted
for this research are one of the first, if not, contemporary UK-based
study to present novel estimates for a group of ill-defined pollutants.
This research demonstrates that linking geochemical data with
electronic primary care medical records can be a valuable approach of
proving whether long term exposure to low-level soil contaminants
may have a health consequence in the population.
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List of publications:
i. Musah A., Gibson JE., Leonardi-Bee J., Cave MR., Ander EL.,
Bath-Hextall F; (2013); Regional variations of Basal Cell
Carcinoma incidence in the UK using THIN database (2004–10);
British Journal of Dermatology; 169 (5): 1093-9; DOI:
10.1111/bjd.12446.
ii. Gibson JE., Ander EL., Cave MR., Bath-Hextall F., Musah A.,
Leonardi-Bee J; (2016); Linkage of national soil quality
measurements to primary care records in England and Wales: a
new resource for investigating environmental impacts on human
health; Population Health Metrics
The above paper has been accepted for publication
Press release(s):
i. South East coast has the highest rates of most common cancer,
study reveals – For immediate release; (23rd May, 2013); British
Association of Dermatologists; Press Release; URL:
http://www.bad.org.uk/media/news?sitesectionid=154&from=0
1/01/2013%2000:00:00&to=01/01/2014%2000:00:00&range=201
3
ii. Wales is UK nation with the highest rates of most common
cancer, study reveals – For immediate release; (23rd May, 2013);
British Association of Dermatologists; Press Release; URL:
http://www.bad.org.uk/media/news?sitesectionid=154&from=0
v
1/01/2013%2000:00:00&to=01/01/2014%2000:00:00&range=201
3
Conference attendance, poster and oral presentations:
i. Musah A, Gibson JE, Leonardi-Bee J, Cave MR, Ander EL, Bath-
Hextall F. 2013. Environmental exposure to soil arsenic and risk
of Basal cell carcinoma in England & Wales (2000 to 2012). 7th
International Workshop on Chemical Bioavailability (3rd – 6th
November 2013) (oral presentation)

ii. Topic: Environmental exposure to soil arsenic and risk of Basal
cell carcinoma in England & Wales (2000 to 2012). EPH seminar
8th July 2013. (oral presentation).

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Acknowledgements
I would like to express special appreciation to my supervisors
Professor Jo Leonardi-Bee and Dr Jack E. Gibson for conceiving this
project, and for securing the funding for this project. I sincerely thank
my supervisors for their continuous support, care of my wellbeing and
the guidance throughout the work. They were always helpful in
guiding me on the path of becoming an independent researcher. They
are the greatest mentors a student could ever have.
I would like to express special thanks to Professor Fiona Bath-Hextall
for her support and contributions in providing me with invaluable
insights on clinical practice and knowledge of NMSCs and BCC. Special
thanks to Dr Mark R. Cave and Dr E. Louise Ander for the technical
support with the G-BASE database, and for their contributions and
insights on principles of geochemistry and geology.
Also, I would like to thank Professor Richard Hubbard and Professor
Joe West for providing me with technical support in managing lung
and gastrointestinal cancer related Read codes, and Dr Yue Huang for
the invaluable training and instructions on implementing data mining
models for this research.
Finally, I would like to give special thanks to parents, my two sisters –
Lalita and Hajra, and my wife Fuseina, for their encouragement, faith
and support whilst I completed this thesis.

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Table of contents
Abstract .......................................................................... i
List of tables .................................................................. xvi
List of figures ................................................................. xxi
List of abbreviations ..................................................... xxxviii
Chapter 1: Introduction ....................................................... 1
1 Background.............................................................. 2
1.1 Metallic elements and their classifications for
carcinogenicity in humans ............................................... 5
1.2 Sources of metallic elements found in soil ................... 8
1.2.1 Mineralogical sources of metallic elements .............. 8
1.2.2 Other external and anthropogenic sources of metallic
elements ............................................................... 12
1.3 Soil contamination in the UK .................................. 12
1.3.1 Brief history on the occurrence of land contamination in
UK ................................................................. 12
1.3.2 Formation of numerical values for soil safety limits and
classification ........................................................... 15
1.3.2.1 UK category 4 screening levels ........................ 16
1.4 The potential health impact of soil metals .................. 20
1.4.1 The exposure pathways from soils to human ............ 22
1.4.1.1 The external exposure from soil to human intake . 22
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1.4.1.2 The internal exposure and uptake by tissues ....... 24
1.4.1.3 Generalised framework of showing the biological
mechanisms and carcinogenic effects of elements from soil ...
............................................................. 25
1.5 Justification for assessing the health impacts of exposure
to low-level soil concentration of metallic elements .............. 28
Chapter 2: Aims & Objectives ............................................... 31
2 Overview of research objectives ................................... 32
2.1 Study 1: Basal cell carcinoma .................................. 33
2.2 Study 2: Lung cancer ............................................ 33
2.3 Study 3: Gastrointestinal tract cancer ....................... 34
Chapter 3: The Health Improvement Network & Geochemical Baseline
Survey of the Environmental Baseline Survey of the Environment .... 35
3.1 The Health Improvement Network ............................ 36
3.2 Geochemical Baseline Survey of the Environment .......... 37
3.3 Linkage of THIN to soil quality data in G-BASE .............. 38
3.3.1 The primary soil data sets .................................. 38
3.3.2 Soil sampling at G-BASE (rural & urban) and NSI(XRFS)
sites ................................................................. 39
3.3.3 Linkage procedure ........................................... 44
3.3.4 Descriptive analysis of geochemical data in THIN-GBASE .
................................................................. 47
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