| Background: Polycyclic aromatic hydrocarbons(PAHs)are a class of volatile organic pollutants that rich in coke-oven emissions(COEs).Long-term exposure to PAHs can lead to a variety of health hazards,including lung cancer and cardiovascular diseases.Telomere,located at the end of the eukaryotic linear chromosome,can protect the chromosome from degradation,end-to-end fusion and recombination to maintain chromosomal stability.Epidemiological studies have confirmed that short telomeres could increase the risk of cancer and cardiovascular disease,thus affecting the long-term viability of the human body.Genetic variants on TERT-CLPTM1 L gene were showed to be associated with leukocyte telomere length(LTL).However,prospective study is scarce for PAHs exposure and their interactions with TERT-CLPTM1 L variants on LTL shortening.Objective: In this study,we aimed to investigate the interaction effects of PAHs exposure and genetic variants in TERT-CLPTM1 L on LTL shortening among coke-oven workers in the cohort study.Methods: We recruited 1628 workers from a coke plant in Wuhan in October 2010.The first follow-up of these subjects were carried out in 2014.Among them,1243 workers were successfully followed up with the follow-up rate of 76.4%.In both baseline(2010)and follow-up(2014)studies,unified questionnaires and health examinations were used to collect the occupational and health information,and the biological samples including blood and urine.The urinary concentrations of 12 monohydroxy PAHs(OH-PAHs)in the baseline study were measured by gas chromatography-mass spectrometry(GC-MS)in order to evaluate the levels of individual baseline PAHs exposure.Because the concentrations of two OH-PAHs were generally below the limit of detection,only ten OH-PAHs were included in our study.We also genotyped six single nucleotide polymorphisms(SNPs)at TERT-CLPTM1 L locus in the studied population.LTL was detected by using real-time PCR assays in both baseline and follow-up blood samples.We used generalized linear models to analyze PAHs exposure and their interaction effects with TERT-CLPTM1 L variants on LTL shortening.Results: We divided all workers into three groups according to the 33.3th and 66.6th percentiles of urinary concentrations of each OH-PAH(T1,T2 and T3 subgroups).After adjusted for potential covariate,significant increasing trends were observed in four-year LTL shortening from T1 to T3 subgroups of 1-OHNap and 1-OHPyr(both FDR P = 0.033).We further analyzed whether TERT-CLPTM1 L variants could modify the associations between baseline PAHs exposure levels and LTL shortening.When stratified by the TERT-CLPTM1 L genotypes,we observed that the association between baseline 1-OHPyr levels and increased LTL shortening was evident among rs2736100 TG+GG genotype carriers(? = 0.380,95%CI = 0.174 ~ 0.587,P < 0.001),but not significant among rs2736100 TT genotype carriers(? =-0.036,95%CI =-0.353 ~ 0.281,P = 0.825).The effect of 1-OHPyr on elevated LTL shortening was significantly shown among rs401681 TT genotype carriers(? = 0.868,95%CI = 0.383 ~ 1.354,P < 0.001),but was marginally shown among rs401681 TC+CC genotype carriers(? = 0.194,95%CI = 0.004 ~ 0.384,P = 0.046).Interaction analysis showed that rs2736100 and rs401681 could significantly interact with baseline 1-OHPyr exposure on LTL shortening among the study participants(Pinteraction = 0.040 and 0.014,respectively).Conclusions: Elevated levels of 1-OHNap and 1-OHPyr exposure at baseline are associated with a significantly increased shortening of telomere length among coke-oven workers,while rs2736100 and rs401681 can significantly modify the effects of telomere length shortening induced by 1-OHPyr. |
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