A Study On The GST And NAT1 Genetic Polymorphisms And Chromosomal Aberrations In The Lung Cancer Cases Of Yunnan Population

Tumour susceptibility is associated with genetic polymorphism of xenobiotics metabolism enzyme and chromosomal aberrations et al. Xenobiotics metabolism enzymes include PhaseⅠenzymes such as Cytochromes P450(CYP450) and Phase Ⅱenzymes such as Glutathione S-Transferase (GSTs) and N-acetyltransferase (NATs). GSTs mainly catalyse many conjugation reactions between glutathione and xenobiotics with electrophilic centres ,forming a more soluble glutathione conjugate that is no longer toxic and may be excreted；NATs catalyses the acetylation of aromatic amines and some heterocyclic amines. Both GSTs and NATs exhibit widely genetic polymorphisms in human population and exit different ethnic frequencies distribution.The deletion in the GSTM1 and GSTT1 genes (null genotype) will lead to absence or less of respective enzyme activities, The association between GSTM1 and GSTT1 null genotype and susceptibility to lung cancer is remained inconclusive;NAT1*10 was conconsidered as fast alleles and some studies show an association between NAT1*10 and bladder, breast and lung cancer. However, the association between NAT1*10 allele, GSTM1null, GSTT1null and lung cancer susceptibility has not been reported in yunnan population. An increased risk of cancer in healthy individuals with high levels of chromosomal aberrations (CAs) in peripheral blood lymphocytes has been described in epidemiological studies,the aberrations on some chromosomes may be considered as the effect biomarker of cancer. To understand the relationship between both genetic polymorphisms of GSTM1,GSTT1,NAT1 and chromosome 15 aberrations and lung cancer development,we conducted a case-control study on lung cancer cases and normal controls coming from Yunnan Province ,in China. We employed polymerase chain reaction (PCR) and normal extracting DNA technology to identify the GSTM1 and GSTT1 genotype; The allelic variants of NAT1 genes were differentiated from the wild-type alleles byPCR-RFLP and AS-PCR methods. Chromosome 15 aberrations were detected by fluorescence in situ hybridisation(FISH). and then employed Yates X2 Corrected test methods ,we had analysed distributive frequencies of GSTM1 and GSTT1 null genotypes, NAT1*10variant alleles and chromosome 15 aberrations among the normal populations and lung cancer population in yunnan province. at the same time ,odd ratio was used to analyse the relative risk of lung cancer. Our studies shows (1) The distributive frequencies of GSTM1null(0/0) genotype among case-conctrol are 73.8% and 63.7%,with no significant difference(P＞0.05) ,but OR of relative risk was 1.6(95%CI=0.88-2.92),so this genotype maybe a moderate lung cancer risk factors.(2) The frequencies of GSTT1null(0/0) among lung cancer cases and normal populathion of yunnan province were 54.1% and 46.8% respectively, no significant difference was seen(P＞0.05),with an odds ratio of 1.3(95%CI=0.47-2.57),so it's a probably slight risk factor .(3) NAT1*10 allels distributive frequencies among case is 81.1% and 74.0% among control population,and having no significant difference with an odds ratio was 1.68(95%CI=0.69-4.08),so this genotype maybe a moderate lung cancer risk factor.(4) The frequencies of chromosome 15 aberrations among case-control population showed an significant difference(P<0.005),with an odds ratio was 1.40(95%CI=1.34-1.47)and a moderate increase of lung cancer risk.It includes structural and number aberration of chromosme,the chromosome structural aberration frequencies 11.65% in case significantly higher than the control (P<0.005), with an odds ratio was 1.39(95%CI=1.28-1.46);and the number aberration frequencies of chromosome 15 were 0.31% and 0.16% among case-control population,a significant difference was seen,and the odds ratio was 1.96 (95%CI=1.44-2.67),both of them were assumable moderate lung cancer risk factors.(5) Combination of GSTM1,GSTT1 and NAT1 genes.* For the combination of GSTM1 and GSTT1, the frequencies of combination GSTM1null and GSTT1null show a significant differenc...