The Role Of Nonclassical MHC Class I Molecule HLA-G In Hepatocellular Carcinoma Familial Aggregation In Guangxi

Background: Hepatocellular carcinoma(HCC)is the most frequent histologic type of liver cancer and its rates vary widely across countries.China is one of the HCC high incidence areas in the world,and the morbidity of HCC in Guangxi province is higher than the national average level of China.Furthermore,HCC familial aggregation,the family has two or more HCC patients,has been frequently observed in Guangxi.Persistent infection with hepatitis B virus(HBV)is a major global risk factor for HCC and it is also thought to be associated with HCC familial aggregation.Only a minor of HBV infections develop to HCC,indicating that HBV infection by itself is not sufficient to explain HCC formation.Increasing evidences have been confirmed that genetic host factors play a critical role in HCC formation during HBV infection.Nowadays,immunosuppressive mechanism has been certified involved in HBV-related HCC,either by suppressing the capacity of the host to overcome HBV infection or preventing the elimination of tumor cells.The host's genetic background that affects the immune response,which may determine those who are at higher risk for developing HCC among HBVinfections.Human leukocyte antigen(HLA)-G is a non-classical HLA class Ib gene and attracts many researchers' interests owing to its pronounced immune-inhibitory properties.Researches showed that HLA-G involved in many disease,such as infectious,autoimmune diseases and cancer.Especially its role in cancer immunoediting has become a hot issue in tumor research.Although there have been many researches revealed the correlations between HLA-G and HCC,the exact nature of HLA-G role in HCC familial aggregation has not been study.On this basis,we conducted this research to investigate the relationship between HLA-G polymorphism and serum sHLA-G levels and familial aggregation for HCC.Methods: 140 family members from families which had two or more HCC patients were selected as the case group.140 age(±5 years),sex,geographical matched family members from families without any cancer patients served as controls.Information including age,gender,race,smoking history,drinking history,main drinking water(tap water,river and well),dietary habits(rice,wheat and corn),family history as well as relationship with the probands were obtained by face-to-face interviews based on a well-designed questionnaire.Whole blood(EDTA tubes)and serum samples were collected from all subjects and stored at-80? to extract DNA and test for sHLA-G by ELISA.Genomic DNA was extracted from the whole blood-EDTA samples by using the DNA Extraction Kit(Invitrogen,Shanghai,China)and the extracted DNA was stored in a freezer at-20? until testing.Genotyping of HLA-G polymorphisms were performed by polymerase chain reaction(PCR).sHLA-G levels in serum samples was measured by Human sHLA-G ELISA kit(Enzo Life Sciences,International Inc).Results:The results show that:(1)The results showed that-14 bp allele(OR=1.70,90%CI=1.17-2.46,P=0.00)and its homozygous-14bp/-14 bp genotype(OR=4.00,90%CI=1.38-11.61,P=0.01)were associated with increased risks of HCC familial aggregation.No significant differences in allele and genotype frequencies were observed for the HLA-G+3142C/G?+3187A/G and HLA-G*0105N polymorphism when comparing cases and controls(all P>0.05).(2)The serum levels of s HLA-G in HCC aggregation family members were higher than that in the controls(median 22.83U/ml vs median 15.45U/ml,P=0.00).(3)The difference of the serum sHLA-G concwentration in different genotype of HLA-G 14 bp ins/del?+3142C/G?3187A/G and HLA-G*0105N polymorphism have not reaching statistical difference(all P>0.05).Conclusion:The results indicated that: The polymorphic site of 14 bp ins/del and the serum levels of sHLA-G may be associtated with susceptibility to HCC familial aggregatio.We have not found the correlation between the HLA-G polymorphisms and the levels of s HLA-G in our subjects.