Association Analysis Of Snps Between LncRNA Colon Cancer Associated Transcript-1 SNP And Gastric Cancer Suseptibility

Gastric cancer(GC)still ranked the fourth in the most common cancers around the world and causing a second mortality.More than 70% GC cases occurred in developing countries and Chinese population accounts for almost 45% alone.Recently years more and more studies have shown a number of risk factors were associated with GC,including smoking history,alcohol intake,unhealthy eating habits,chronic H.pylori infection and family history of cancer.Long noncoding RNAs(lnc RNAs)have participated in the key process of carcinogenesis,including cancer cell proliferation,apoptosis and migration.A wealth of studies have revealed that the indispensable role of lnc RNA and their genetic variants in the development of cancers.Moreover,the susceptibility genes may play a crucial role in the occurrence and development of GC and the association between single nucleotide polymorphisms(SNPs)and risk of GC has been reported.Objective This study aimed to evaluate the association between four haplotype tagging SNPs(ht SNPs)(rs77628730,rs6989575,rs7816475 and rs6470502)and GC in Chinese people,and examine the gene–environment factor interaction on GC susceptibility for further study.We also aimed to find the susceptive genes and provide cancer biomarkers for early detection and early diagnosis of GC.In order to provide the theoretical basis for the regulatory mechanism of lnc RNAs polymorphisms,we further investigated the association between its genotypes and CCAT1 expression in plasma.Methods Combined with several human lnc RNA database and major domestic and foreign literature databases,four haplotype tagging SNPs of CCAT1(rs77628730,rs6989575,rs7816475 and rs6470502)were selected.460 GC cases were all newly confirmed by histopathological examination and 460 healthy controls had no self-reported cancer-free randomly selected from a community and frequency-matched with cases in terms of age(±5 years)and sex.The genotyping of rs77628730 and rs6470502 were finished with polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)and rs6989575,rs7816475 were genotyped by created restriction site PCR(CRS-RFLP)assays.All primers were designed with Primer 6.0 software.The data were analyzed by statistical package for the Social Sciences version 21.0.Demographic characteristics and genotype frequencies of the four selected SNPs in case and control groups were compared with student's t test and Chi-squared(?2)test.The categorical variables were expressed as numbers and percentages.All significant tests were 2-tailed,and P<0.05 were considered as statistically significant.The Hardy-Weinberg equilibrium(HWE)was determined by using the goodness-of-fit ?2 test.The unconditional logistic regression was performed to estimate the associations between genetic polymorphisms and the risk of GC adjusted the age,sex,smoking status,alcohol history and family history of cancer.Furthermore,we used Multifactor Dimensionality Reduction 2.0(MDR2.0)to assess the potential interactions among gene and environment factors.This study also conducted the Haplotype analysis using the online SHEsis(http://analysis.bio-x.cn/my Analysis.php).Results of q RT-PCR analysis were expressed as mean ±standard deviation(SD).Results After adjusted for age,sex,smoking status,alcohol consumption and family history,the association were still significant for individuals with TT genotype(ORadjusted: 1.68;95% CI: 1.01-2.79)compared with subjects with CC genotype.Stratified analysis performed that the increased risk of GC associated with the rs6470502 variant allele was significant among those with age >50(P=0.04,ORadjusted = 1.69,95% CI=1.01-2.98)and those who ever smoked(P=0.01,ORadjusted = 1.95,95% CI=1.41-2.89).Compared with wild genotype of rs7816475,the combined AG+GG genotype of rs7816475 had a significantly increased risk of GC among the subgroup with family history of GC(P=0.03,ORadjusted = 1.74,95% CI=1.30-2.87).The result of q RT-PCR revealed that the expression of CCAT1 m RNA in plasma with rs6470502 TT(2.08±0.55),TC(1.70±0.38)and TC+TT(1.95±0.40)genotype were higher than the group with rs6470502 CC genotype(1.45±0.34).(P<0.05)The gene-environment interactions of four SNPs(rs77628730,rs6989575,rs7816475,rs6470502)with smoking,alcohol drinking and family history of GC showed smoking,rs77628730 A allele,rs6989575 T allele and rs6470502 T allele could increase the risk of GC(OR=3.83,95%CI=2.96-4.96).Conclusion CCAT1 rs6470502 T allele and TT genotype could increase the risk of GC and rs7816475 G allele could decrease the risk of GC.rs6470502 CT+TT genotype was associated with groups aged >50 years old and smokers.rs7816475 AG+GG genotype was associated with subjects with family history.The mutation of CCAT1 rs6470502 could increase CCAT1 m RNA expression.The gene-environment interactions of smoking,rs77628730,rs6989575 and rs6470502 could increase the risk of GC.