Association of twelve polymorphisms in three onco-lncRNA genes with hepatocellular cancer risk and prognosis:A case-control study

AIM To evaluate the association of 12 tag single nucleotide polymorphisms(tag SNPs) in three onco-long non-coding RNA(lnc RNA) genes(HOTTIP,CCAT2,MALAT1) with the risk and prognosis of hepatocellular cancer(HCC). METHODS Twelve tag SNPs covering the three onco-lnc RNAs were genotyped by the KASP method in a total of 1338 samples,including 521 HCC patients and frequencymatched 817 controls. The samples were obtained from an unrelated Chinese population at the First Hospital ofChina Medical University from 2012-2015. The expression quantitative trait loci(e QTL) analyses were conducted to explore further the potential function of the promising SNPs. RESULTS Three SNPs in HOTTIP,one promoter SNP in MALAT1,and one haplotype of HOTTIP were associated with HCC risk. The HOTTIP rs17501292,rs2067087,and rs17427960 SNPs were increased to 1.55-,1.20-,and 1.18-fold HCC risk under allelic models(P = 0.012,0.017 and 0.049,respectively). MALAT1 rs4102217 SNP was increased to a 1.32-fold HCC risk under dominant models(P = 0.028). In addition,the two-way interaction of HOTTIP rs17501292-MALAT1 rs619586 polymorphisms showed a decreased effect on HCC risk(P interaction = 0.028,OR = 0.30) and epistasis with each other. HOTTIP rs3807598 variant genotype showed significantly longer survival time in HBV negative subgroup(P = 0.049,HR = 0.12),and MALAT1 rs591291 showed significantly better prognosis in female and HBV negative subgroups(P = 0.022,HR = 0.37; P = 0.042,HR = 0.25,respectively). In the study,no significant effect was observed in e QTL analysis. CONCLUSION Specific lnc RNA(HOTTIP and MALAT1) SNPs have potential to be biomarkers for HCC risk and prognosis.

TLR3 gene polymorphisms in cancer:a systematic review and meta-analysis

Introduction:Recent studies examining the association of Toll-like receptor 3(TLR3)gene polymorphisms with the risk of developing various types of cancer have reported conflicting results.Clarifying this association could advance our knowledge of the influence of TLR3 single nucleotide polymorphisms(SNPs)on cancer risk.Methods:We systematically reviewed studies that focused on a collection of 12 SNPs located in the TLR3 gene and the details by which these SNPs influenced cancer risk.Additionally,14 case-control studies comprising a total of7997 cases of cancer and 8699 controls were included in a meta-analysis of 4 highly studied SNPs(rs3775290,rs3775291,rs3775292,and rs5743312).Results:The variant TLR3 genotype rs5743312(C9948T,intron 3,C>T)was significantly associated with an increased cancer risk as compared with the wild-type allele(odds ratio[OR]=1.11,95%confidence interval[CI]=1.00–1.24,P=0.047).No such association was observed with other TLR3 SNPs.In the stratified analysis,the rs3775290(C13766T,C>T)variant genotype was found to be significantly associated with an increased cancer risk in Asian populations.Additionally,the rs3775291(G13909A,G>A)variant genotype was significantly associated with an increased cancer risk in Asians,subgroup with hospital-based controls,and subgroup with a small sample size.Conclusion:After data integration,our findings suggest that the TLR3 rs5743312 polymorphism may contribute to an increased cancer risk.