Association Between Polymorphisms Of CTLA-4?IL-10 Gene And Breast Cancer In Chinese Han Population

Objective: Breast cancer is the most common malignancy threatening the health and life of women. The incidence of breast cancer has been increasing rapidily in recent years. The etiology of breast cancer is not completely known, but the role of genetic factors has been well documented. The host immunogenetic background plays an important role in the development of breast cancer. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) and interleukin-10 (IL-10) all are multifunctional cytokine, which play varied roles in cancer pathogenesis with increasing evidence suggesting their involvement in tumour initiation, growth and metastasis. To evaluate the role of CTLA-4?IL-10 gene polymorphisms in breast cancer, a population-based case-control study was conducted in Han women of China.Methods: A case-control study which included 315 cases of breast cancer and 322 cancer-free subjects as a control group was conducted to detect CTLA-4 and IL-10 single nucleotide polymorphisms. All subjects were collected from the Shan Dong Tumor Hospital and the PLA 456 hospital. CTLA-4 and IL-10 genotypes were identified using PCR-restriction fragments length polymorphism technique (PCR-RLFP). The adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate logistic regression.Results:CTLA-4 gene -1661A/G -318C/T genotype distribution were significantly different between patients and controls, and The frequency of -1661 G allele -318 T allele carriers was significantly higher in patients than in controls (p=0.011; p=0.003). Stratified analysis showed that the postmenopausal cases with -1661 G allele -318 T allele were at an increased risk for beast cancer(OR 2.05, 95% CI 1.17-3.37; OR 2.23, 95% CI: 1.22-3.65). There were no signi?cant differences in genotype, allele, or haplotype frequencies in -1082?-819?-592 loci of IL-10 gene between patients and healthy controls.Association with tumor prognostic or predictive factors was also observed with certain genotypes: the CTLA-4 gene -1661 AA genotype was associated with lesser lymph node involvement (p=0.018), and the IL-10 -1082 AA genotype with higher lymph node involvement (p=0.041) and higher tumor stage(p=0.039). Furthermore, in the haplotype analysis of IL-10 gene, we found that patients carrying ATA haplotype were in higher lymph node involvement (p=0.022) and higher tumor stage(p=0.028) of breast cancer at the time of diagnosis compared with others.Conclusion:The above findings indicate that polymorphisms of the CTLA-4 gene may modify individual susceptibility and progression of breast cancer in Chinese Han women. These results also suggest that polymorphisms of the IL-10 gene promoter variants participate in the progression of breast cancer rather than in its initial development.