Associations Between SNPs In Estrogen-related Genes And Risk And Survival Of Malignant Tumors

Objective:To evaluate the relationship between single nucleotide polymorphism (SNP) in estrogen-related genes and risk of esophageal squamous cell carcinoma (ESCC).Materials and methods:Three SNPs were selected including ESR2rs4986938, ESR2rs1256049, CYP1B1rs1056836.310ESCC and473control were genotyped by MGB-Taqman method. Multivariate logistic regression models were used to investigate associations between genotypes and the risk of ESCC. We also did a subgroup analysis by gender. Odds ratio (OR) and95%confidence interval (CI) were calculated to show the relative risk. SPSS version16.0software was used for the analyses.Results: Adjusted by gender, age, smoking and drinking, ESR2rs1256049was associate with the risk of ESCC under recessive genetic model, the result showed that ESR2rs1256049CC/CT was associated with increased risk of ESCC (P=0.002, OR=2.370,95%CI=1.390-4.043). After the subgroup analysis by gender, we found that ESR2rs1256049CC/CT was also associated with increased risk of male ESCC (P=0.005, OR=2.396,95%CI=1.303-4.043). However, no association were observed between ESR2rs4986938, CYP1B1rs1056836genotypes and the risk of ESCC.Conclusions:Polymorphism of ESR2rs1256049may be associated with the risk of ESCC in Chinese Han population. Background: In the worldwide, colorectal cancer (CRC) is a common malignant tumor. Epidemiologic studies have suggested that gender difference is a common feature of colorectal cancer, both in incidence and in the development of cancers. Studies have suggested that estrogens appear to play a role in CRC carcinogenesis. It is reported that single nucleotide polymorphisms (SNPs) in estrogen-related genes were associated with CRC risk. However, the association between these SNPs and CRC overall survival (OS) is rare. We want to investigate the association between the polymorphisms of estrogen-related genes and the overall survival of colorectal cancerPatients and methods:Genomic DNA was extracted from355colorectal cancer, ESR1rs9340799, ESR1rs2234693, ESR2rs4986938, ESR2rs1256049, CYP1B1rs1056839and CYP17rs743572were selected. Trends in OS over time were analyzed with the Kaplan-Meier method, and log-rank tests were used to identify potential differences in OS between the subgroups. Hazard ratios (HRs) were estimated with a multivariate Cox proportional hazards model and adjusted for potentially predictive factors such as age, sex, smoking status, chemotherapy and clinical disease stage.Results:At univariate analysis, CYP1B1rs1056836was associate with the overall survival of CRC (log-rank P=0.016). Multivariate Cox regression analysis showed that CYP1B1rs1056836CG/GG genotypes were associated with poor OS among CRC (70.6m vs.83.0m, HR=1.628,95%CI=1.039-2.551). In the rectal cancer subgroup analysis, similar results were observed, CYP1B1rs1056836CG/GG genotypes were also associated with poor OS (HR=1.689,95%CI=1.006-2.836, P=0.018).Conclusion: Our results suggested that CYP1B1rs1056836variant might be used to improve prediction of treatment outcome of CRC. Background Epidemiological characteristics differences between men and women with lung cancer, and better response to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) among female non-small-cell lung cancer (NSCLC) patients suggests that genotype variants of enzymes in estrogen biosynthesis and metabolism may be associated with these differences.Methods We did a three-stage investigation. First, six SNPs from4genes in estrogen biosynthesis and metabolism pathway were genotyped to evaluated their associations with lung cancer risk in599lung cancer cases and704controls. Second, above six SNPs were further evaluated their roles in the overall survival (OS) of another235patients with advanced NSCLC treated with Gefitinib/Erlotinib. Third, we did above two analyses among female neversmokers subgroup which is a special model in lung cancer development and TKI treatment.Results The CYP1B1rs1056836CG/GG genotype was associated with increased risk of lung cancer (P=0.043, odds ratio [OR],1.339,95%confidence interval [CI],1.009-1.778). It also conferred a poorer OS for advanced NSCLC patients treated with TKI (P=0.011, adjusted hazard ratio [HR],1.667,95%CI,1.126-2.468). Moreover, in the female neversmokers subgroup, individual harboring the rs1056836CG/GG genotypes had a high risk of lung cancer(P=0.030, OR,1.744,95%CI,1.056-2.879), and also conferred a poor OS than CC genotyped (P=0.030, HR,1.931,95%CI,1.064-3.505).Conclusion CYP1B1rs1056836variant may be used to refine the selection of patients expected to respond to EGRR-TKI treatment and predict lung cancer susceptibility, especially among female nonsmokers. These findings require validation in larger prospective trials and thorough mechanistic studies.