Exposure, telomere length, and cancer risk

Telomeres are tandem repeats of TTAGGG at the end of eukaryotic chromosomes. Telomeres play a key role in chromosome stability and regulation of the cellular lifespan. Telomeres are shortened during cell division, and probably, by not yet well characterised factors in the environment. Short telomeres in peripheral blood have repeatedly been associated with increased risk of various types of cancer, as well as with cardiovascular diseases, diabetes, and lung diseases. The aim of this thesis was to explore the effect of exposures on telomere length in different occupational or environmental settings, and also to investigate the association between telomere length and chromosomal aberrations in blood, a biomarker for cancer risk. Different study populations were recruited to elucidate specific hypothesises: In the first study 157 workers in rubber industry were recruited to investigate the effect of exposure to rubber fumes on telomere length; in the second study 101 welders, 34 diesel-exposed workers and 127 controls were examined to elucidate the effect of exposure to particles on telomere length; in the third study 202 women exposed to arsenic via drinking water were analysed for effects of arsenic exposure on telomere length; and finally, in the fourth study 364 male adults were recruited to study the association between telomere length and chromosomal instability. Associations between exposures and telomere length were found: N-nitrosamines were related to shorter telomeres, whereas welding fumes and diesel exhaust showed no significant impact on telomere length. Arsenic in drinking water was related to longer telomeres and the association between arsenic and telomere length was modified by polymorphisms in the main arsenic-metabolizing gene. Although telomere length was associated with chromosome instability, no significant association was found between telomere length and cancer risk in our study, probably due to the limited number of cancer cases. We also found effects of exposure on methylation of DNA, and in turn with chromosome instability, reflecting interactions of the environment with epigenetic processes. The findings of the thesis provide evidence that some exposures, at workplaces or in the general environment, influence the average telomere length in peripheral blood. Since telomeres are key components for genomic stability and often altered during malignant transformation, it is likely that the effect of the exposures on telomeres found here reflect a mechanism of carcinogenesis for the compounds studied