Principal Investigator: Dr Laura Horsfall
Institution: University College London (UCL)Tags: 5167, prediction, respiratory, Risk
Human blood contains various small molecules with potent antioxidant properties including bilirubin, uric acid, vitamin C, vitamin E and beta-carotene and raised serum levels have been independently associated with a reduced risk of respiratory disease. However, whether these relationships are causal remains to be proven. Furthermore, the role of these molecules in improving risk stratification has not been evaluated.
The aims of the research are to establish whether people with genetically lower levels small-molecule antioxidants have worse respiratory and endothelial function and whether serum bilirubin and urate measures have any role in improving lung cancer prediction in smokers. Knowledge on whether serum antioxidants are causally related to respiratory/endothelial function could help us understand why some smokers succumb to respiratory disease while others remain comparatively healthy. In turn, this could help GPs identify high-risk smokers and detect lung cancer at an earlier stage by targeting chest screening. The research could also identify potential therapeutic targets for the primary prevention of respiratory diseases. Using the full cohort, we will investigate whether genetic variants known to influence levels of the five named antioxidants in section 1a above are also associated with baseline measures of respiratory function and arterial stiffness. We hypothesize that any effects will be stronger in smokers exposed to high levels of antioxidants and thus will test for interactions with smoking status. We will then investigate whether measuring bilirubin and uric acid levels can improve lung cancer risk prediction. Full cohort
Project extension – December 2019
The aims of the research projects are to establish whether people with genetically lower levels small-molecule antioxidants have an increase risk of cardiopulmonary events and worse respiratory/endothelial function relative to people with genetically higher levels. We also plan to investigate whether serum bilirubin and uric acid measures have a role in improving respiratory cancer prediction in smokers. We will also use the results of recently published GWAS’ of lung cancer to examine whether the addition of replicated genotype loci can improve existing prediction models over and above the addition of bilirubin and uric acid. Finally, in support of the findings of a larger study using electronic health records of 4 million UK patients, we request to report in a separate publication the time trends in respiratory cancer incidence in UK Biobank by smoking status as a smaller replication study.
Last updated Dec 17, 2019