The Study Of The Relationship Between Single Nucleotide Polymorphisms Of FAS(L) And Susceptibility And Prognosis Of Lymphoma

FAS / FASL system signaling pathway plays an important biological role in apoptosis.The distribution of FAS in many different types of cell surface involved in apoptosis signal transduction,when its natural ligand FASL receives the signal of its conduction apoptotic,will initiate a death signal cascade that eventually leads to apoptosis.The polymorphism on the promoter region of the FAS/FASL gene may affect the expression of the gene by affecting the binding of the transcription factor,and may contribute to the development or progression of the tumor when the expression of FAS is reduced or the expression of FASL is increased.In recent years,there have been some studies on the relationship between the susceptibility and prognosis of three Single nucleotide polymorphisms(SNP)sites,FAS-1377G/A,FAS-670A/G and FASL-844T/C,on the promoter region of FAS/FASL gene,But the results are inconsistent,which may be different from the selected population or different tumor.There is no report on the correlation between FAS(L)gene SNPs and the susceptibility and prognosis of lymphoma.The distribution frequencies of FAS(L)gene SNPs in different populations were different.We collected 667 samples of peripheral blood from healthy people with no history of cancer and no blood relationship in Southern China.Polymerase chain reaction(PCR)was used to detect FAS and FASL gene promoter polymorphisms,which can restricted fragment length polymorphism(PCR-RFLP),and chi-square(?2)test was used to compare the allele frequency distribution among different populations.The results showed that the allele frequencies of FAS-1377 G,FAS-670 A and FASL-844 T were 48.61%,59.03% and 27.67% in Southern China.The genotypes of the three polymorphic loci were consistent with the Hardy-Weinberg law.The frequency of FAS-1377 G/A allele was significantly different from that in different countries and regions,while FASL-844 T/C allele frequencies were significantly different from those in India,Egypt,Iran and Tunisia(P<0.05),and no significantly different from other countries and regions.And there was no significant difference in FAS-670A/G allele frequencies among different countries and regions.Lymphoma is a kind of malignant tumor originated from lymphatic hematopoietic system,with high morbidity and mortality.In recent years,the incidence tends to be younger.We collected 271 cases of malignant lymphoma(HL)in peripheral blood samples of patients of susceptibility of lymphoma.We selected 271 healthy individuals from the healthy population of South China who were matched with the age sex of lymphoma patients,and used the unconditional logistic regression method to analyze the relationship between the SNPs of the FAS / FASL gene promoter region and the susceptibility to lymphoma of various types.The results showed that FAS-670 A / G have the relationship with B cell lymphoma.The risk of exposure to A allele(including AA and GA genotype)was twice(OR = 2.126,95%CI = 1.165-3.877;P = 0.012)as high as that of GG genotype,and the risk of DLBCL Also increased by 2.3 times(OR = 2.349,95%CI = 1.204-4.583;P = 0.01).In the female population,the susceptibility to DLASL in the FASL-844 TT genotype population was increased(OR = 2.890,95%CI = 1.018-8.197,P = 0.039)compared with the population bearing the FAS-844(CC + TC)genotype,and FAS-1377G/A has not yet found the relationship with the susceptibility to lymphoma(P>0.05).We selected 127 patients with complete clinical and prognostic data in DLBCL patients with lymphoma for prognostic analysis,and used Cox-regression method and Kaplan-Meier survival curve to research the relationship between FAS-1377G/A,FAS-670A/G and FASL-844T/C and the survival and efficacy of DLBCL patients.The results showed that FAS-670 A / G could affect the efficacy of DLBCL in patients Under the similar solution treatment.FAS-670 A could significantly increase the remission rate of patients(OR = 0.241,95% CI = 0.058-0.996,P = 0.037).Survival analysis showed that compared with patients with FAS-670 GG genotype DLBCL,carrying the FAS-670 A allele reduced progression free survival time(HR=1.637,95%CI=1.019-2.630,P=0.042).There was no significant effect of single SNP on overall survival in DLBCL patients.However,DLBCL patients who were concurrently carrying FAS-1377 A / A and FASL-844 C / C genotypes had worse overall survival than DLBCL patients who did not carry either of them(HR = 3.366,95% CI = 1.145-9.894,P = 0.027).In conclusion,there were FAS-1377G/A,FAS-670A/G and FASL-844C/T polymorphisms in the population of South China,and the frequencies of FAS-1377G/A and FASL-844T/C genes were significantly different in different populations.FAS-670 A / G can significantly affect the susceptibility,efficacy and progression-free survival of DLBCL,but,the combination of FAS-1377 G / A and FASL-844 T / C significantly affected the overall survival of DLBCL patients,Suggesting that three SNPs can be used as indicators of DLBCL susceptibility or prognosis,applied to in the prevention of lymphoma and personalized treatment.This paper needs to further expand the sample size for analysis and verification.