OBJECTIVEThis study aimed to understand the correlation between tag single nucleotide polymorphisms (tSNP) of microRNA regulatory genes and the gentic susceptibility of primary liver cancer.

METHODS1:1 case-control study was applied in this research. A total of 532 primary liver cancer patients in 2 teaching hospitals in Zhengzhou city were enrolled as case group.532 healthy individuals were enrolled as control group. The subjects were surveyed by a face-to-face interview and 5 ml of peripheral venous blood were collected. Candidate tSNP were screened from DICER1, RAN and GEMIN4 gene, respectively. PCR-RFLP or Allele specific PCR was applied for genotyping of the subjects. Conditional logistic regression model and Multifactor-Dimensionality Reduction method were applied for analyzing the correlation between tSNP of above genes and gentic susceptibility of primary liver cancer. The gene-environment interaction was also analyzed.

RESULTSThe frequencies of genotype CC, CT, TT in rs14035 locus were 67.29% (358/532), 28.20% (150/532), 4.51% (24/532) in case group, and 70.30% (374/532), 28.20% (150/532), 1.50% (8/532) in control group, respectively (χ2=8.35, P<0.05). The frequencies of genotype GG, GA, AA in rs1045491 locus were 71.05% (378/532), 26.69% (142/532), 2.26% (12/532) in case group, and 80.45% (428/532), 18.42% (98/532), 1.13% (6/532) in control group, respectively (χ2=13.17, P<0.01); the frequencies of genetype GG, GT, TT in rs2291778 locus were 53.38% (284/532), 40.23% (214/532), 6.39% (34/532) in case group, and were 25.94% (138/532), 63.91% (340/532), 10.15% (54/532) in control group (χ2=83.71, P<0.01). TT genotype in rs14035 locus (OR=2.54, 95%CI: 1.19-6.32) and GA genetype in rs1045491 locus (OR=1.74, 95%CI: 1.08-2.66) were susceptible genotype of primary liver cancer, whereas GT (OR=0.52, 95%CI: 0.43-0.75) and TT genotype (OR=0.62, 95%CI: 0.46-0.86) in rs2291778 locus were protective genotype. Haplotype analysis showed that haplotype 3 (AACTGGGT) (OR=1.42, 95%CI: 1.10-1.82) and haplotype 5 (AGCCAGCC) increased the risk of occurrence of primary liver cancer (OR=1.36, 95%CI: 1.02-1.80), whereas haplotype 2 (AACTATCC) (OR=0.69, 95%CI: 0.52-0.91) and haplotype 6 (AACTGTGT)(OR=0.61, 95%CI: 0.45-0.81) decreased the risk. Subjects exposed to allele A of rs1045491, allele T of rs14035 and HBV infection intend to be the high risk population of primary liver cancer (OR = 3.72, 95%CI: 2.38 - 5.56).

CONCLUSIONGenotypes of TT in rs14035 locus, and GA in rs1045491 locus may be susceptible genotypes of liver cancer carcinogenesis. T allele in rs2291778 locus is a non-susceptible allele of primary liver cancer. Combined effects of multigene alleles and multi-locus genotype may have a synergistic role in the carcinogenesis of liver cancer.