| Objective: (1) to investigate the association between HPV infection and the etiology of Kazakh ESCC in Xinjiang in China. (2) To investigate the relationship of LMP2/LMP7 Gene Polymorphisms between susceptibility in Xinjiang Kazakh ESCC. (3) To investigate the association between the polymorphism of LMP (1ow molecular weight proteasome) and HPV infection with Kazakh ESCC in Xinjiang .Methods: (1) HPV infection was detected in 316 Kazakh ESCC and 66 normal esophageal mucosa cases archived paraffin-embedded tissues by polymerase chain reaction(PCR) and validated them by sequencing PCR product selected randomly in the 316 samples. (2) LMP2/LMP7 genotypes were detected by a PCR-based RFLP(Restriction Fragment Length Polymorphism) assay in 168 samples with Kazakh ESCC and 283 population cancer-free controls in the same area. Theχ~2 test was adopted to check the differences in genotype distribution between cases and controls, and Hardy-Weinberg equilibrium was tested in the group.Results: (1) The positive rate of HPVL1, 16, 18, 31, 45E7 and multi-infection in Kazakh esophageal carcinoma is 64.6%, 41.1%, 25.3%, 14.2%, 7.3%,17.7% respectively. The positive rate of HPVL1, 16, 18, 31, 45E7 and multi-infection in Kazakh"nomal"esophageal mucosa is 18.2%, 15.2%, 9.1%, 4.5%, 1.5%,4.5% respectively, except HPV45, there is significant difference between ESCC and NE (P<0.05) with HPV16, 18, 31, L1 infection and multi-infection. (2) According to the layer statistics of pathological materials, the positive rate of HPV18 in low differentiated ESCC is higher than well differentiated ESCC. (3) The frequencies of R/R,R/C and C/C in LMP2 were 41.07%, 48.81% and 10.12% in Kazakh's individuals with ESCC respectively. They were significant different from controls (61.48%, 34.28% and 4.24%)(χ~2=19.43,P<0.05);So the frequencies of LMP2 R/C and C/C genotype in patients were higher than that in controls [ odds ratio 2.13 (95% confidence interval1.42~3.20);3.57 (95% confidence interval1.62~7.87)].Heterogenous or homologous respectively comparison the LMP2 R/R genotype. (4) The frequency of Q/Q,Q/K and K/K in LMP7 was 81.55%, 14.88% and 3.57% in Kazakh's individuals with ESCC respectively, and 68.55%, 29.68% and 1.77%in Kazakh controls respectively, there was significant difference between them(χ~2=13.39,P<0.05), So wild heterogenous (Q/K) might decrease the risk of ESCC comparison the homologous (Q/Q)]. (5) The association between the polymorphism of LMP2/LMP7 and HPV infection and pathological grades in Kazakh ESCC was analized, There were no statistical differences (LMP2χ~2=1.672,P=0.43>0.05, LMP7χ~2=1.182,P=0.55>0.05).. (6) To analyisis between LMP2/LMP7 haplotype and Kazakh ESCC,the LMP2 mutation genotype/LMP7 homologous increase the risk of Kazakh ESCC.Conclusions: (1) HPVDNA infection is associated with Kazakh ESCC in Xinjiang.HPV16,18 were the mainly risk genotype. There was correlation between HPV18 infection and the development of Kazakh ESCC. (2) The polymorphisms of LMP2/LMP7 gene is associated with Kazakh esophageal carcinoma. LMP2 R/R,R/C genotypes may be the susceptibility genes, while LMP7 Q/ K gene may be the protect genotype. (3) It indicate that LMP2/LMP7 gene polymorphisms and HPV infection which might not be associated with each other but are frequently involved as integral parts of multi-step process that lead to development of esophageal carcinoma.
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