Dataset Information

Genetic variants of lncRNA HOTAIR and risk of epithelial ovarian cancer among Chinese women.

ABSTRACT: Ovarian cancer is one of the common female malignant tumors globally. However, exactly mechanism of ovarian cancer remained unknown. HOTAIR, a lncRNA in the mammalian HOXC locus, has been fully explored for its genetic variants, expression level and carcinogenesis, development and progression of multiple cancers, except for ovarian cancer. In this study, we hypothesized that abnormal expression of HOTAIR and common variants of HOTAIR are associated with risk of Epithelial ovarian cancer (EOC). We first evaluated the HOTAIR levels in 100 paired tissues of EOC patients and corresponding normal tissues. Results showed that the expression level of HOTAIR in EOC tissues was significantly higher than that in corresponding normal tissues. Then the genotyping analyses of HOTAIR gene was conducted in a Chinese population. The results indicated that rs4759314 and rs7958904 were significantly associated with EOC susceptibility. For rs4759314, the difference between the G allele (as the reference) and the A allele was statistically significant (adjusted OR, 1.34; 95% CI: 1.08-1.65; P = 6.8 × 10-3). For rs7958904, C allele was associated a significantly decreased EOC risk when compared with G allele (OR: 0.77; 95% CI: 0.67-0.89; P = 4.2 × 10-4). The study identified that HOTAIR variants could be a useful biomarker for the predisposition to EOC and for the early diagnosis of the disease.

SUBMITTER: Wu H

PROVIDER: S-EPMC5173041 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Genetic variants of lncRNA HOTAIR and risk of epithelial ovarian cancer among Chinese women.

Wu Haijing H Shang Xiaofei X Shi Yu Y Yang Zhirong Z Zhao Jun J Yang Min M Li Yan Y Xu Shiqiang S

Oncotarget 20160701 27

Ovarian cancer is one of the common female malignant tumors globally. However, exactly mechanism of ovarian cancer remained unknown. HOTAIR, a lncRNA in the mammalian HOXC locus, has been fully explored for its genetic variants, expression level and carcinogenesis, development and progression of multiple cancers, except for ovarian cancer. In this study, we hypothesized that abnormal expression of HOTAIR and common variants of HOTAIR are associated with risk of Epithelial ovarian cancer (EOC). W ...[more]

PMID: 27166268

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Project description:Purpose:HOX transcript antisense RNA (HOTAIR) plays important roles in carcinogenesis of various kinds of malignant tumors, including lung cancer. Single nucleotide polymorphisms (SNPs) in HOTAIR were reported to be associated with susceptibility of several kinds of cancers. The present study assessed the associations between three SNPs (rs4759314, rs12826786, and rs920778) and lung cancer susceptibility, as well as gene-environment interaction between smoking exposure and the polymorphisms. Patients and methods:A case-control study including 551 patients and 543 healthy controls was performed. The associations between SNPs and lung cancer susceptibility were assessed by logistic regression model. Results:rs4759314 was observed to increase the susceptibility of lung cancer, lung adenocarcinoma, squamous lung cancer, and small cell lung cancer statistically significantly (OR of 4.048 for lung cancer; 3.584 for lung adenocarcinoma; 4.671 for squamous lung cancer; 4.502 for small cell lung cancer). In stratified analysis for sex and smoking exposure, rs4759314 GG and AG genotype was also observed to increase the risk of lung cancer statistically significantly (OR of 5.221 for male; 3.491 for female; 3.653 for nonsmoking individuals; 4.458 for smoking individuals). Results of gene-environment interaction analysis showed that there was no interaction between smoking exposure and rs4759314 on additive scale. Results of logistic regression model suggested that the interaction between smoking and rs4759314 was statistically significant on multiplicative scale. rs12826786 CT genotype carriers and T allele could decrease the risk of developing lung cancer (OR of 0.751 for CT carriers; 0.785 for T allele), and in dominant model, TC and TT genotype carriers also have a 0.249-fold decrease risk compared with CC genotype carriers. In stratified analysis for smoking exposure, TC and TT have a 0.432-fold decreased risk compared with CC genotype carriers. Conclusion:HOTAIR rs4759314 and rs12826786 were associated with lung cancer susceptibility in Chinese Han population.

Project description:INTRODUCTION: Recently, several genome-wide association studies (GWAS) have identified novel single nucleotide polymorphisms (SNPs) associated with breast cancer risk. However, most of the studies were conducted among Caucasians and only one from Chinese. METHODS: In the current study, we first tested whether 15 SNPs identified by previous GWAS were also breast cancer marker SNPs in this Chinese population. Then, we grouped the marker SNPs, and modeled them with clinical risk factors, to see the usage of these factors in breast cancer risk assessment. Two methods (risk factors counting and odds ratio (OR) weighted risk scoring) were used to evaluate the cumulative effects of the five significant SNPs and two clinical risk factors (age at menarche and age at first live birth). RESULTS: Five SNPs located at 2q35, 3p24, 6q22, 6q25 and 10q26 were consistently associated with breast cancer risk in both testing set (878 cases and 900 controls) and validation set (914 cases and 967 controls) samples. Overall, all of the five SNPs contributed to breast cancer susceptibility in a dominant genetic model (2q35, rs13387042: adjusted OR = 1.26, P = 0.006; 3q24.1, rs2307032: adjusted OR = 1.24, P = 0.005; 6q22.33, rs2180341: adjusted OR = 1.22, P = 0.006; 6q25.1, rs2046210: adjusted OR = 1.51, P = 2.40 × 10-8; 10q26.13, rs2981582: adjusted OR = 1.31, P = 1.96 × 10-4). Risk score analyses (area under the curve (AUC): 0.649, 95% confidence interval (CI): 0.631 to 0.667; sensitivity = 62.60%, specificity = 57.05%) presented better discrimination than that by risk factors counting (AUC: 0.637, 95% CI: 0.619 to 0.655; sensitivity = 62.16%, specificity = 60.03%) (P < 0.0001). Absolute risk was then calculated by the modified Gail model and an AUC of 0.658 (95% CI = 0.640 to 0.676) (sensitivity = 61.98%, specificity = 60.26%) was obtained for the combination of five marker SNPs, age at menarche and age at first live birth. CONCLUSIONS: This study shows that five GWAS identified variants were also consistently validated in this Chinese population and combining these genetic variants with other risk factors can improve the risk predictive ability of breast cancer. However, more breast cancer associated risk variants should be incorporated to optimize the risk assessment.

Dataset Information

Genetic variants of lncRNA HOTAIR and risk of epithelial ovarian cancer among Chinese women.

Publications

Genetic variants of lncRNA HOTAIR and risk of epithelial ovarian cancer among Chinese women.

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