Association Of Interleukin Genes Polymorphisms With Breast Cancer Genetic Susceptibility And Clinicopathological Features In Shaanxi Han Population

OBJECTIVE: Breast cancer is the most common malignancy in women worldwide and the highest mortality rate among gynecologic tumors.The occurrence and development of breast cancer is a complex process influenced by many factors,among which genetic factors play an important role.The aim of this study was to explore the association between interleukin gene polymorphism and the risk of breast cancer in Shaanxi Han population,and to select susceptibility genes related to the risk of breast cancer,providing theoretical support for the pathogenesis of breast cancer.METHODS: Peripheral blood was collected from 553 breast cancer patients and 550 normal controls in Shaanxi,and then the genomic DNA in the blood was extracted.Seventeen single nucleotide polymorphisms(SNPs)on the five interleukin genes were genotyped using the Agena Mass ARRAY platform.The relationship between SNPs and breast cancer risk was evaluated by chi-square test and genetic analysis model.Results: 1.The relationship between SNPs and the risk of breast cancer: overall analysis found that rs10213865,rs969129,rs6451231 and rs10213865 on IL7 R gene and rs55692658 on IL9 gene were significantly correlated with the increased risk of breast cancer.rs12722498(IL2RA)is associated with reduced risk of breast cancer.Haplotype analysis showed that CGAG and ATAG haplotypes on IL7 R genes(rs10213865,rs969129,rs118137916 and rs10053847)were significantly associated with reduced risk of breast cancer.Stratified analysis showed that rs6451231(IL7R)was associated with an increased risk of breast cancer in the > 52-year-old population.Both rs77179660(IL7R)and rs12722498(IL2RA)were significantly associated with reduced risk of breast cancer in patients aged between 52 years.In the stratification of the left breast tumor,rs10213865,rs969129,rs6451231,rs55692658(IL9)and rs2281089(IL2RB)on the IL7 R gene were all associated with increased risk of breast cancer.rs12569923(IL2RA)is associated with increased risk of breast cancer in right breast tumor stratification.2.The relationship between SNPs and pathological characteristics of breast cancer: rs791588 was correlated with age of menarche over 14 years in breast cancer patients.rs1573673 and rs12722498 were correlated with tumor volume ?2cm in patients with breast cancer.rs77179660 was correlated with the low grade of tumor staging in breast cancer patients,while rs1872072 was correlated with the high grade of tumor staging in breast cancer patients.rs2281089 was negatively correlated with lymph node metastasis in breast cancer patients.rs12569923 was correlated with Estrogen receptor upregulation in breast cancer patients,while rs2281089 and rs9607418 were correlated with down-regulated ER expression in breast cancer patients.rs3218264 was correlated with up-regulated PR(Progestrone receptor)in breast cancer patients,while rs10213865 and rs9607418 were correlated with down-regulated PR in breast cancer patients.The up-regulated Ki67 expression in rs117173992 and rs2281089 breast cancer patients was correlated with the down-regulated Ki67 expression in rs969129,rs55692658,rs77179660 and rs1573673.Conclusion: This study preliminarily concluded that the polymorphisms of IL7 R,IL7,IL9,IL2 RA and IL2 RB genes were correlated with the risk of breast cancer among Han women in Shaanxi province.Although the results of this study need to be verified by a large number of samples,the results of this study provide new insights into the molecular genetic mechanism of breast cancer.