Interaction between air pollution and host factors in lung cancer

Abstract

Ambient air pollution is a worldwide health problem. In present, nearly four million people die every year prematurely due to the effects of air pollution, where the deaths are mostly related to cardiovascular (80%) and respiratory diseases (20%), including lung cancer. However, the pathways in which air pollution increases the risk of lung cancer are not well understood yet. The overall aim of this research is to examine the interaction of air pollution and host factors (genetic polymorphism and DNA damage/repair activity) in lung cancer patients and controls. Exposure to air pollution was estimated for the study population through two modelling methods: IDW and UKAAQIM. Generally, there was a trend of decreasing air pollution levels within the region of NWM over time (through both estimation methods) although some areas remained with high air pollutants levels (above the standard limit values). Under the multivariate analysis, PM2.5 exposure and three SNPs of GPR126 gene (rs11155242, rs3817928 and rs7776375) were found to be significantly association with lung cancer risk. For the PM2.5 exposure, the odds ratio (OR) = 12.72, 95% CI= 3.36-48.23 (PM2.5 12.5-15.0 µg/m3) and 10.08, 95% CI= 2.24-45.42 (PM2.5 >15.0 µg/m3). For the SNPs of GPR126 gene, on the other hand, the heterozygous genotypes of rs11155242, rs3817928 and rs7776375 were significantly associated with decreased risk for lung cancer (the commonest homozygous genotype as a reference). Their corresponding ORs were 0.41 (95% CI= 0.3-0.7; p= 0.001), 0.43 (95% CI= 0.3-0.7; p= 0.001) and 0.48 (95% CI= 0.3-0.8; p= 0.003), respectively. However, no significant associations were found for the least homozygous genotypes of the above three SNPs. Further, no evidence was found for any interactions between air pollutants (including PM2.5) and genetic polymorphism (including the three SNPs of GPR126 gene) in relation to lung cancer risk. Furthermore, no significant differences were found (in DNA adducts; N7-MG) or DNA repair proteins activity levels) between the individuals with different air pollution exposure levels.Overall, ambient air pollution (especially PM2.5 exposure) can be considered as an independent risk factor for lung cancer even at lower levels of exposure. However, the risk for lung cancer might be modified through the interaction between the ambient air pollution and host factors (e.g. genetic polymorphism and DNA repair activity). However, further research with larger sample number is needed to examine the environment-gene interactions.

Date of Award	1 Aug 2017
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Andrew Povey (Supervisor) & Richard Booton (Supervisor)