Principal Investigator: Mr Tom Dudding

Institution: University of Bristol

Summary:

Conditions that effect the mouth, teeth, throat and neck such as tooth decay, mouth ulcers and gum disease are very common and other diseases in this part of the body such as oral cancer typically have poor outcomes. Despite this there is limited research into these important conditions. This work aims to use UK Biobank to investigate what factors in the environment and of the persons (their genetics or body composition) are linked to these conditions. It will also try to find out which of these factors are the ones that cause someone to have that disease as this may help doctors, dentists and researchers to develop new treatments or provide better advice to their patients. The project will initially be for 3 years which will allow for different diseases to be investigated uses multiple different techniques. Depending on the findings in the first 3 years there may be a need to extend the project if further work is required. We hope the project will be able to improve the quality of information provided to the general public relating to these conditions so that they can make choices to reduce their chances of getting these conditions, be more aware of these conditions and receive better quality care if they develop these conditions.

Project extension:

Study Question (SQ) 1) What are the environmental and host (genetic and other disease) causes of oral health disease?

Study Question 2) What are general health and well-being implications of oral health disease?

Study Question 3) Are previously unknown factors associated with oral health disease?

This study will use a range of traditional epidemiology, genetic epidemiology and causal methods to investigate SQ 1 and 2.

-Oral health diseases:

-dental disease (proxied by denture wearing and missing teeth)

-oral ulceration

-skin cancers

-head and neck cancers/pre-malignancy

-any other oral disease identifiable by HES procedure or diagnosis data (e.g. wisdom tooth removal)

Environmental and host factors:

-Environmental – all (non-bulk data) available in UK Biobank such as: diet, socio-economic status, etc

-Host – Genetic, other diseases, BMI, etc

SQ1) Presence of causal associations of environmental and host factors on oral health outcomes:

-Prospective cohort design

-BMI –> oral cancer incidence

-Nested case control study

-GWAS oral ulceration

-Mendelian randomization

SQ2) Implications of oral health disease on general health and well being:

-Prospective cohort design

-effect of denture wearing have on incidence of cardiovascular disease

-Nested case control study

-Is tooth loss associated with type II diabetes

SQ3)

A hypothesis free approach will be adopted to assess for factors previously not assessed in relation to oral health diseases using an untargeted approach. We will conduct a series of phenomewide association studies (PheWAS), using methods generated within the MRC Integrative Epidemiology Unit that are specific for UK Biobank, with oral health diseases as the exposure. We will also utilise machine learning methods to help identify previously untested risk factors.

Skin cancers including melanoma and non-melanoma skin cancer i.e. basal cell carcinoma and squamous cell carcinoma are already included in our application. We wish to also include such skin cancers from other sites outside the head and neck in our analysis. No further data will need to be requested and analysis will remain the same as described in the above in the current scope.

Facial ageing is likely to be a marker of dermal integrity and ultraviolet barrier function. We wish to include facial ageing in hypothesis free analysis testing for genetic or environmental risk factors for dermal integrity, and test for causal association between facial ageing and skin cancer. No further data will need to be requested and analysis will remain the same as described in the above in the current scope

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Last updated Apr 24, 2019