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A Study On The Relationship Between Genetic Polymorphisms Of GSTP1and CYP1A1and Susceptibility To Lung Cancer

Posted on:2010-04-03Degree:MasterType:Thesis
Country:ChinaCandidate:Q YinFull Text:PDF
GTID:2234330392952277Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Objective To investigate the polymorphisms of the CYP1A1exon7and GSTP1(Ile105Val) genes in the Mongolian and Han nationality populations in Inner Mongolia region, and ex-plore the relationship between polymorphisms of CYP1A1and CSTP1genes、 gene-gene (CYP1A1-GSTP1) or gene-environment (CYP1A1-smoking, GSTP1-smoking) inter-actions and susceptibility to lung cancer is Hun nationality population. Methods Allele Specific Pulymerase Cham Reaction (AS-PCR) was performed to genotype polymorphisms of the CYPlA1and GSTP1among216subjects of healthy Han Nationality and212subjects of healthy Mongolien Nationality. A case-control study of116lung cancer patients and216healthy controls was conducted to investigate the polymorphisms of GSTP1and CYP1A1genes, gene-gene and gene-environment interactions in Han nationality populations in Inner Mongolia region. Results(1)The genotype frequencies of the CYP1A1and CSTP1poly-morphisms among the Mongolian nationality populations: those of GSTP1(AA),(AC) and (GC) wen:47.2%、50.0%and2.8%; those of CYF1A1(Ile/Ile),(Ile/Val) and (Val/Val) were16.5%、70.8%and12.7%. The genotype frequencies of the CYP1A1and GSTP1palymorphiams among the Han nationality populations: the GSTP1gotiotype frequencies were S1.9%(AA)、44.0%(AG) and4.1%(CC); the CYP1A1genotype fanniencies were20.4%(Ile/Ile),61.6%(Ile/Val) and18.0%(Val/Val). No significant difference found among the Mongolian and Han nationality populations in the CYP1A1or GSTP1tupes in Inner Mongolia region(P>0.05).(2) The proportions of smokers in the lung cancer and control group in Han Nationality of Inner Mongolia were64.7%and47.2%, te-spectively. The Chi-square teste showed there was significant difference between the two groups (P<0.05). The sroolcera had a2.04-fold increased rink of lung cancer than nonsouk-(?)(95%CI=1.284-3.225),(3) compared with the control group,the odd ratio for CYP1A1(Ile/Val) in lung cancer patients was1.460(95%CI=0.780-2.733), and for CYP1A1(Val/Val) was1.593(95%CI=0.74S-3.393),but the Chi-square testa showed no significant difference between this two graups(P>0,05), In individuals with the combined cigarette smoking and the CYP1A1(Ile/Ile) or (Ile/Val+Val/Val) genotype, the risk of lung cupcer was approximately].57or2.64times that of persons who both cany the CYP1A1(Ile/Ile) gettotype and do not smoke, Similarly, the risk was a1.23-fold for the combined CYP1A1(Ile/Val+Val/Val) genotype and non-smoking. The combined CYP1A1(Ile/Val+Val/Val) genotype and smoking were found to be a significant risk factor of lung canc-er.(P<0.05).(4) The genotype frequencies of the GSTP1polymorphisms (AA、AG、GG) in control group were51.9%、44.0%、4.1%; Among the lung cancer group,the frequencies were53,4%、44.0%、2.6%.The Chi-aquam tests showed no significant difierence among this two groups (P>0.05).In individuals wilh the combined cigarette smoking and the GSTP1(AA) or (AG+GC) genotype,the risk of lung cancer was approximately1.76or1.86times that of persons who both carry the GSTF1(AA) genotype and do not smoke. The Chi-square teats showed no significant dffierence among this two groups (P>0.05),(5) We ob-served that combioations of the CYP1A1(Ile/Val+Val/Val) and GSTP1(AA) or (AC+CG) genotypes although led to1.418or1.343fold inoreased risk of lung cartcer compared with the combiruition of GSTP1(AA)/CYP1A1(Ile/Ile),the Chi-aquare teste showed there was no statislical significance(P>0.05). Condusions No significant difference was found between the Mongolian and Han nationality populations in the CYP1A1or GSTP1ganfitypes in Inner Monpolia region(P>0.05); We found that the CYP1A1(Ile/Val) and CYP1A1(Val/Val) were suspicious risk factors of lung cancer in the study on the relationship between genet-ic polymorphisms of GSTP1and CYP1A1and susceptihllity to lung cancer. Smoking was the susceptibility factor of lung cancer. An association with susceptibility to long cancer between CYP1A1and GSTP1was out found rn Han Nationality of Inner Mongolia, Cumbining CYP1A1(Ile/Val+Val/Val) and smoking could ineretse the risk af lung cancer, This illustrated that there was synergatic effect between CYP1A1(Ile/Val+Val/Val) and smoking on the rence of lung cancer.
Keywords/Search Tags:CYP1A1, GSTP1, atnoking, gene polymorphisms, susceptibility to lungcancer
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