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Title: Environmental exposure to metallic soil elements and risk of cancer in the UK population, using a unique linkage between THIN and BGS databases
Author: Musah, Anwar
ISNI:       0000 0004 6425 814X
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2017
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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 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 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 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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QV Pharmacology