Approved research

The role of serum-based small molecule antioxidants in preventing and predicting age-related phenotypes and respiratory cancer

Lay summary

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