Indoor air pollution, tobacco smoke, genetic variants, chromosome biomarkers, and risk of lung cancer in rural and urban China.

摘要

In less developed countries, air pollution is a major concern as biomass fuels are often used for cooking and heating homes1. Up to 90% of all rural households continue to use unprocessed or under-processed fuels which can contain large quantities of toxic compounds2. Coal exhaust inhalation leads to a substantial increase in risk of lung cancer and is classified as a group 1 carcinogen3,4. Tobacco smoke accounts for 80% of all lung cancers5. Cooking oil emissions contains various genotoxins and mutagens and is considered a group 2a carcinogen 3,6-10. Genome-wide association studies have independently linked three regions of the genome (15q25, 5p15, 6p21)11 and molecular studies have characterized chromosomal biomarkers12,13 with lung cancer risk. Interactions between these characteristics with air pollution have not been readily assessed. To address shortcomings in the knowledge of these interactions, three projects were carried out.;In the first project, the results suggest that the effect of tobacco on lung cancer risk was weaker in men exposed to higher amounts of coal and higher risk coal types. This is the first study to evaluate the effect of tobacco smoking on lung cancer risk by the quantity and type of coal used. Constituents of coal combustion, such as polycyclic aromatic hydrocarbons, could plausibly act to diminish the carcinogenicity of tobacco through metabolic competition or other mechanisms, and as indoor exposures are reduced by improved ventilation or elimination of coal use in homes, the adverse effects of tobacco will become more obvious, highlighting the importance of smoking cessation.;For the second project, a prospective cohort study of non-smoking Chinese women suggested that long-term exposure to poor ventilation and coal use in poorly vented conditions increased the risk of lung cancer. These findings were consistent with past retrospective case-control studies which suggested that past exposure to poorly ventilated coal posed a health risk. These results suggest that current modern day cooking conditions, particularly in poorly ventilated homes, is still a public health issue in urban and modern day China.;Lastly, the third project was the first study to find the effect of ETS modified by TERT (rs2736100), for lung cancer risk. The effect of ETS could be underestimated in portions of the population with the higher risk TERT alleles. These results suggest that common variation in genes can modify the relationship of indoor air pollution and lung cancer risk, and may underestimate how significant of an impact risk factors, such as ETS, could have on a subset of the population with genetic susceptibility.