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Breast cancer is the most common malignancy in women, accounting for about 23% of all malignant tumors. Although China belong to the low incidence of breast cancer District, but in recent years, the incidence of breast cancer was the trend of rapid growth, especially in Shanghai, Beijing, Tianjin and coastal areas, the incidence of breast cancer has been the highest in the female cancer incidence or second place. Breast cancer has become one of the major disease threat to women's health in China. The pathogenesis of breast cancer is very complex, now widely recognized that the incidence of breast cancer development is the result of the interaction of genes and environment, but the exact cause is not yet clear. Different genetic background of the individual under the same environmental exposure risk of breast cancer, suggesting that genetic background differences may affect individual susceptibility to breast cancer. Such genetic background differences in the general population, mainly for the difference of the genomic sequence. High breast cancer have been identified codominant gene BRCA1, BRCA2 and ATM, but these high codominant gene mutations explain only about 5% of breast cancer, researchers say most of the breast cancer susceptibility with low codominant gene common genetic variation. Therefore, an urgent need to find a low codominant associated with breast cancer susceptibility gene. The genome-wide association studies (Genome-wide Association Study, GWAS) has become a complex disease found low common dominant gene for susceptibility loci powerful tools. In June 2007, Easton et al first reported the results of a breast cancer genome-wide association studies, the study found five breast cancer susceptibility region, the most significant of which is associated with breast cancer is located in FGFR2 (rs2981582) and TNRC9 (rs3803662 ) gene polymorphism. FGFR2 belongs to the tyrosine kinase receptor, can start a cascade of reactions, through the adapter protein / enzyme cascade regulating transcription factors activate the transcription of genes, inducing cell proliferation, differentiation, and migration, FGFR2, including breast cancer in within a variety of tumors are highly expressed. TNRC9 may belong to the high mobility group protein (High Mobility Group, HMG) family, HMG proteins in chromatin structure, regulation, and regulation of gene expression and cell proliferation and differentiation and other aspects play an important role TNRC9 expression in breast cancer patients with malignant metastasis even greater. Therefore, we speculate that of FGFR2 and TNRC9 the single nucleotide polymorphisms (Single Nucleotide Polymorphism, SNPs) may be associated with the Chinese population of the breast cancer susceptibility. This study intends to adopt a case-control study design, through a combination of macro-epidemiology and molecular epidemiology research tools, applications SNPs detection technology, combined with a breast cancer traditional risk factors, in order to filter out the breast cancer-related genetic susceptibility markers , which provide a scientific basis for the screening of high-risk groups and early diagnosis of breast cancer and early treatment. The first part of FGFR2 gene polymorphisms and susceptibility to breast cancer association study FGFR2 belongs to the tyrosine kinase receptor involved in cell proliferation, differentiation, angiogenesis in physiological and pathological processes play an important role in tumor development. FGFR2 expression in breast cancer, estrogen receptor (ER)-dependent. GWAS found in intron 2 of the FGFR2 gene genetic variation (rs2981582, rs1219648 and rs2420946) significantly associated with risk of breast cancer, its the polymorphic changes will affect individual susceptibility to breast cancer. Therefore, we assume that the FGFR2 gene polymorphism is associated with breast cancer risk of Chinese population. [Objective] To explore the Chinese crowd into a relationship of fibroblast growth factor receptor FGFR2 gene polymorphism and breast cancer susceptibility, especially strong the relationship between breast cancer susceptibility and endogenous estrogen exposure. [Methods] A case control study, to histologically confirmed 1,058 cases of new-onset breast cancer patients and 1,078 patients with no history of cancer in age and region matched community controls, application by Beckman SNPstream genotyping in the Han population in Jiangsu, China The platform detected three the FGFR2 gene polymorphic loci (rs2981582, rs1219648 and rs2420946). [Results] 1 unit point of breast cancer associated analysis rs2981582, rs1219648 and rs2420946 genotype distribution in the case and control groups were significantly different (rs2981582: P = 0.004; rs1219648: P = 0.010; rs2420946: P = 0.032 ), the variant genotypes of the three sites are significantly increased risk of breast cancer (rs2981582: OR = 1.36, 95% CI = 1.14-1.62; rs1219648: OR = 1.31, 95% CI = 1.09-1.58; rs2420946: OR = 1.32,95% CI = 1.10-1.59). Multilocus joint analysis and hierarchical analysis at the same time carrying FGFR2 3 variant genotype (rs2981582 CT / TT 36% rs1219648 AG / GG and rs2420946 CT / TT) increased risk of breast cancer than other individuals ( Adjust OR = 1.36, 95% CI :1.13-1 .62, P = 0.0009), the effect of the ER / PR positive (OR = 1.62,95% CI = 1.26-2.09), premenopausal (OR = 1.60, 95% CI = 1.23-2.07) and the first live births older (≥ 25 years) (OR = 1.45,95% CI = 1.14-1.84) women are more significant. 3. Interaction analysis FGFR2 the joint genotype (rs2981582 CT / TT rs1219648 AG / GG and rs2420946 CT / TT) and menopausal status additive interaction (P = 0.037) in the incidence of breast cancer. [Conclusion] The study results show that the FGFR2 gene polymorphisms may play an important role in breast cancer growth in the Chinese population by ER / PR way, its potentially susceptible markers of breast cancer as the crowd. Association studies of the second part TNRC9 gene polymorphism and breast cancer susceptibility genome-wide association study found TNRC9 change gene polymorphism may be associated with the genetic predisposition for breast cancer. TNRC9 containing HMG structure, and by the minor groove of the DNA-binding surface, so that the DNA bending reconciliation spiral, thereby adjusting the structure of the chromatin, exercise function. Therefore, we assume that TNRC9 gene polymorphism is associated with breast cancer risk of Chinese population. [Objective] To investigate the relationship between the Chinese crowd TNRC9 gene polymorphism and breast cancer susceptibility. [Method] China Jiangsu Han population case-control study, no history of cancer of the 1,058 new cases of breast cancer patients with histologically confirmed 1,078 cases of age and region matched community controls, application the Beckman companies SNPstream genotyping type platform TNRC9 gene over three polymorphic loci (rs3803662, rs12443621 and rs8051542) were detected. [Results] 1 unit Point of breast cancer associated with the analysis of the distribution of alleles and their genotypes between the case and control groups were no significant differences (rs3803662: P = 0.151; rs1244362: P = 0.644; rs8051542: P = 0.737). Univariate and multivariate logistic regression analysis showed that TNRC9 gene and three SNPs (rs3803662, rs12443621 and rs8051542) with breast cancer risk, there is no significant association (the dominant model for rs3803662: OR = 1.00, 95% CI = 0.76-1.30; rs12443621: OR = 1.12,95% CI = 0.90-1.40; rs8051542: OR = 1.13,95% CI = 0.94-1.35). Stratified analysis of breast cancer according to age, age at menarche, age of live births, menopausal status and family history layered, three sites in each subgroup to be significantly associated. Stratified results of the ER / PR status, rs12443621 and rs8051542 dominant model effect in ER-positive individuals are associated with breast cancer (rs12443621: OR = 1.38, 95% CI = 1.01-1.88; rs8051542: OR = 1.26,95% CI = 0.99-1.60). [Conclusion] The study found that rs12443621 and rs8051542 two-bit point may increase the risk of ER-positive breast cancer in Chinese population.
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