Epidemal Growth Factor Gene Polymorphisms Associated With Susceptibility To Hepatocellular Carcinoma

Object:To investigate the relation of the EGF five polymorphisms, which include G61A in 5'UTR,S16R in exon 1,R431K in exon8, I708M in exon 14 and D784V in exon 15,of HCC risk.Methods:The strategy is the genetic association study based on the candidate gene. This study included two independent case-control populations (respectively called"Guangxi case-control population"recruited from Fusui County and its surrounding regions at Guangxi Province and"Jiangsu case-control population"recruited from Haimen County at Jiangsu Province) and one set of nuclear familie (called"Guangxi nuclear family population"recruited from Guangxi Cancer Hospital).Genomic DNA was extracted from peripheral blood leukocytes of 5ml whole blood of all participants by means of standard prodedures. All samples were tested using a polymerase chain reaction restriction fragment length polymorphism technique(PCR-RFLP). Many softwares such as Hardy-Weinberg test 3.0\ PHASE2.0\SNPSTATS\SPSS10.0 were used in statistical analysis.Results:(1) adjusting for age\sex\smoking\drinking,and so on, there was no significant difference in the genotype distributions of the four exons polymorphisms studied by logistic regression analyses in Guangxi case-control population.(2)In Guangxi case-control population,by Logistic analysis,the combined GA/AA variant genotypes were associated with a significantly decreased risk of HCC(adjusted OR=0.749,95%CI:0.568-0.988,P=0.041). The significant association was validated in another case-control populations from Jiangsu province(OR=0.652,95%CI:0.432-0.985,P=0.042).Combined two case- -control populations, Logistic regression analysis demonstrated that the genotypes with A allele was significantly associated with decreased hepatocellular carcinoma after adjusting for age, sex, smoking, drinking, and so on (A/G and A/A vs G/G;OR=0.710,95%CI: 0.566-0.892,P=0.003). Additional, three hundred and thirty-six subjects from 112 nuclear families were recruited at Guangxi province. By TDT test, Allele A showed significantly decreased transmission to the HCC affected individual(χ2=7.674, P=0.005). (3) We use the AliBaba2.1 software finding that EGF G61A G allele compared A allele provide binding motifs for the transcription factor SP1.Conclusions: (1) No significant association between genotype distributions of the exon four polymorphisms including S16R in exon1, R431K in exon 8, I708M in exon 14,D784V in exon 15, and HCC was found.(2) The EGF G61A AG/AA genotypes may be genetic protected factor for the occurrence of HCC in Chinese patients. Our findings suggest that the genetic polymorphism in EGF may play an important role in mediating susceptibility to hcc in Chinese populations.