Study On The Association Between The Changes Of Telomere Length And The Risk Of Lung Cancer And COPD In Population Exposed To Heavy Soot

Research Background:In Xuanwei City,Yunnan Province,China,lung cancer(LC)and chronic obstructive pulmonary disease(COPD)have extremely high morbidity and mortality,which is related to indoor air pollution caused by bituminous coal burning.Previous studies have shown that the relative telomere length of peripheral blood leukocytes is associated with the risk of LC and COPD.Telomeres are a small segment of the end of chromosomes in eukaryotes,maintain the stability of chromosomes,and the length of telomeres is regulated by genes.At the same time,studies have shown that genetic factors also play an important role in the development of LC and COPD,mainly reflected in single nucleotide polymorphisms(SNPs).Research purposes:The purpose of this study was to investigate the correlation between the relative telomere length of peripheral blood leukocytes and the risk of LC and COPD in Xuanwei population,the effects of smoking and bituminous coal exposure on the relative telomere length.Meanwhile,the association of the polymorphism of the TERT gene rs7705526 and rs2853677 loci with the risk of diseases,and hance to provide a theoretical basis for predicting the risk of LC and COPD.Research method:The study selected a case-control study method.The study subsects were LC and COPD patients and health controls collected at Xuanwei First People’s Hospital in 2018.A total of 216 LC patients,296 COPD patients and 425 healthy controls were included.Peripheral venous blood samples from each subject were collected and DNA was extracted from leukocyte.The relative telomere lenthes(RTL)were measured by using quantitative polymerase chain reaction(qPCR),and SNPs loci in TERTgene were analyzed.Logistic regression model was used to analyze the relationship between the relative telomere length and the risk of LC and COPD,and the association of TERT gene rs7705526 and rs2853677 loci polymorphism with susceptibility to LC and COPD.Research result:Study on the relationship between telomere length and LC and COPD risk:The relative telomere length of peripheral blood leukocytes in LC patients was 0.76±0.35(Mean±SD),which was significantly shorter than that in healthy controls 0.95±0.39(P<0.001),and the relative telomere length of peripheral blood leukocytes in COPD patients was 0.81±0.35 was significantly shorter than the telomere length of the healthy control group(P<0.001).After adjustment for gender,age,smoking status and bituminous coal use,logistic regression analysis was performed.Relative to the telomere length tertiles,individuals with the shortest telomere lengthes were 3.90 and 4.54 times high risks of development of LC and COPD respectively Risk(P<0.001).The age of LC and COPD subjects had a negative correlation with the relative telomere length(P<0.05),but the age in the control group showed no correlation with relative telomere length.In COPD patients,telomere length was associated with exposure to bituminous coal and FEV1(P<0.001).Association analysis of genetic polymorphisms in TERT gene with telomere length and susceptibility to LC and COPD:1)Under the genetic model,logistic regression results show that the genotype rs7705526 in the Dominant genetic model C/A and A/A is associated with an increased risk of LC.The rs7705526 genotype C/C and C/A in Additive genetic model was associated with a reduced risk of COPD.Under the Additive genetic model,the A/G and G/G of rs2853677could increase the risk of lung cancer in Xuanwei,Yunnan.2)No significant correlation between telomere length and gene polymorphism was found.Analysis conclusion:In Xuanwei,Yunnan,the shortening of the relative telomere length of human peripheral blood leukocytes are associated with the risk of LC and COPD.People with shorter relative telomere lengths have a greater risk of LC and COPD.This could be caused by the large amount of smoke exposures in Xuanwei.At the same time,rs7705526 and rs2853677 of the TERT genes were associated with an increased risk of LC and COPD,while rs2853677 was associated with decreased risk of COPD in Xuanwei population in Yunnan.Telomere length is a potential indicator of LC and COPD.