Association Analysis Of SNPs Within LincRNA Sequences And Breast Cancer Susceptibility

Objective Breast cancer causes an ever-increasing cancer burden for women’s health with the molecular mechanism unclear.The role of non-coding RNA in the initiation and progression of breast cancer is becoming far more evident and long intergenic non-coding RNA(linc RNA)is a new hot spot in this field after micro RNA.Genome-wide association study(GWAS)indicated the association between linc RNA and cancers.To reveal the association between SNPs within linc RNA sequences and breast cancer risk and prognosis,we designed a large case-control study in China,detecting differences between the distribution of breast cancer patients and the normal people.Methods We performed a case-control study including 1484 breast cancer cases diagnosed by pathologists in 2006-2009 and followed more than 5 years,and 1678 controls from breast cancer screening community.We genotyped 17 SNPs within 6 linc RNAs(HOTAIR、MALAT1、ANRIL、H19、HOTTIP、HULC)sequences using Taqman assays,and analyzed the association with different genotype of genes and breast cancer susceptibility.In addition,we further analyzed the correlation between SNPs and breast cancer risk according to environment factors,which were acquired from questionnaires.Meanwhile,based on clinical and follow-up data of breast cancer patients,we investigated the impact on the prognosis of breast cancer patients depending on SNPs of linc RNA sequence.Results 1.In the correlation analysis between case and control,we found that H19(rs2071095)AA genotype has a protective effect of breast cancer(OR=0.64;95%CI:0.49-0.83)compared with CC genotype,and ANRIL(rs2151280)GGgenotype can increase more risk of breast cancer(OR=1.29;95%CI:1.02-1.63)than AA genotype.2.Our results were further stratified by environmental factors finding that ANRIL(rs2151280)GG genotype can increase more risk of breast cancer than AAgenotype in the group of>50-years old,BMI<24 kg/m~2,non-menopause,oralcontraceptive,abortion and smoking,the OR(95%CI)was 1.46(1.09,1.97),1.66(1.15,2.39),1.38(1.01,1.88),2.40(1.39,4.15),1.41(1.04,1.90)and 1.41(1.04,1.90),respectively.H19(rs2071095)AA genotype has a protective effectof breast cancer compared with CC genotype in the group of non-oralcontraceptive,no-smoking,no-breast benign disease history and no-familyhistory of tumor,the OR(95%CI)was 0.65(0.49,0.86),0.63(0.49,0.82),0.82(0.69,0.97)and 0.53(0.40,0.72),respectively.3.We found no significant statistics relationship between SNPs and prognosis ofbreast cancer.But we found that the risk effect of ANRIL(rs2151280)GGgenotype was more pronounced than AA in the subjects who have TNM(0+Ⅰ)stage(OR=1.57;95%CI:1.07-2.29);And the onset age of breast caner with theAA genotype of H19(rs2071095)has a trend early than 50 years old(OR=1.49;95%CI:1.00-2.22).Conclusion 1.We identified the relationship of the SNPs of H19 and ANRIL and breast cancerrisk a breast cancer risk in Chinese women.The variants can be used as potentialbiomarkers to predict the susceptivity of breast cancer.Although we have finished5 years follow-up of all the cases,the study found no significant statisticsrelationship between SNPs and prognosis of breast cancer because breast cancerhas better prognosis and the number of the death counted less than 10%.So thatwe need to prolong the follow up period to obtain more reliable results.