Dataset Information

Common genetic variation in the Estrogen Receptor Beta (ESR2) gene and osteoarthritis: results of a meta-analysis.

ABSTRACT: BACKGROUND:The objective of this study was to examine the relationship between common genetic variation of the ESR2 gene and osteoarthritis. METHODS:In the discovery study, the Rotterdam Study-I, 7 single nucleotide polymorphisms (SNPs) were genotyped and tested for association with hip (284 cases, 2772 controls), knee (665 cases, 2075 controls), and hand OA (874 cases, 2184 controls) using an additive model. In the replication stage one SNP (rs1256031) was tested in an additional 2080 hip, 1318 knee and 557 hand OA cases and 4001, 2631 and 1699 controls respectively. Fixed- and random-effects meta-analyses were performed over the complete dataset including 2364 hip, 1983 knee and 1431 hand OA cases and approximately 6000 controls. RESULTS:The C allele of rs1256031 was associated with a 36% increased odds of hip OA in women of the Rotterdam Study-I (OR 1.36, 95% CI 1.08-1.70, p = 0.009). Haplotype analysis and analysis of knee- and hand OA did not give additional information. With the replication studies, the meta-analysis did not show a significant effect of this SNP on hip OA in the total population (OR 1.06, 95% CI 0.99-1.15, p = 0.10). Stratification according to gender did not change the results. In this study, we had 80% power to detect an odds ratio of at least 1.14 for hip OA (? = 0.05). CONCLUSION:This study showed that common genetic variation in the ESR2 gene is not likely to influence the risk of osteoarthritis with effects smaller than a 13% increase.

SUBMITTER: Kerkhof HJ

PROVIDER: S-EPMC2997092 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Common genetic variation in the Estrogen Receptor Beta (ESR2) gene and osteoarthritis: results of a meta-analysis.

Kerkhof Hanneke J M HJ Meulenbelt Ingrid I Carr Andrew A Gonzalez Antonio A Hart Deborah D Hofman Albert A Kloppenburg Margreet M Lane Nancy E NE Loughlin John J Nevitt Michael C MC Pols Huibert A P HA Rivadeneira Fernando F Slagboom Eline P EP Spector Tim D TD Stolk Lisette L Tsezou Aspasia A Uitterlinden André G AG Valdes Ana M AM van Meurs Joyce B J JB

BMC medical genetics 20101116

<h4>Background</h4>The objective of this study was to examine the relationship between common genetic variation of the ESR2 gene and osteoarthritis.<h4>Methods</h4>In the discovery study, the Rotterdam Study-I, 7 single nucleotide polymorphisms (SNPs) were genotyped and tested for association with hip (284 cases, 2772 controls), knee (665 cases, 2075 controls), and hand OA (874 cases, 2184 controls) using an additive model. In the replication stage one SNP (rs1256031) was tested in an additional ...[more]

PMID: 21080949

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Project description:PURPOSE: Estrogen receptor alpha (ERα, encoded by ESR1) is a well-characterized transcription factor expressed in more than 75% of breast tumors and is the key biomarker to direct endocrine therapies. On the other hand, much less is known about estrogen receptor beta (ERβ, encoded by ESR2) and its importance in cancer. Previous studies had some disagreement, however most reports suggested a more favorable prognosis for patients with high ESR2 expression. METHODS: To add further clarity to ESR2 in breast cancer, we interrogated a large population-based cohort of primary breast tumors (n=3207) from the SCAN-B study (Sweden Cancerome Analysis Network—Breast [SCAN-B], ClinicalTrials.gov identifier: NCT02306096). Spearman rank correlation was used to determine correlations between expression of ESR1 and ESR2. Kruskal-Wallis non-parametric test and Wilcoxon rank sum test were used to compare and plot expression of the ESR1 and ESR2 genes in various clinical groups such as PAM50 subtype and age groups in both the SCAN-B and TCGA cohorts. Transformed ESR2 expression data was divided into tertiles, with the first tertile defined as ESR2-high, and the bottom two tertiles at ESR2-low. Mann Whitney U test and Fisher’s exact test were used to evaluate significant differences in the clinicopathological variables for the ESR2-high and ESR2-low groups. Survival analysis was performed by Kaplan-Meier and Cox regression survival analyses that included a median follow-up of 6.2 years (IQR = 2.2). RESULTS: Using RNA-seq data, we found that ESR2 is expressed at low levels overall with a slight inverse correlation to ESR1 expression (Spearman R = -0.18, p = 2.2e-16), and highest ESR2 expression in the basal- and normal-like PAM50 subtypes. ESR2-high tumors had favorable overall survival (p=0.006), particularly in subgroups receiving endocrine therapy (p=0.03) and in triple-negative breast cancer (p=0.01). These results were generally robust in multivariable analyses accounting for patient age, size, node status, and grade. Gene modules consistent with immune response were associated to ESR2-high tumors. CONCLUSIONS: Taken together, our results indicate that ESR2 is generally expressed at low levels in breast cancer but associated with improved overall survival and may be related to immune response modulation.

Dataset Information

Common genetic variation in the Estrogen Receptor Beta (ESR2) gene and osteoarthritis: results of a meta-analysis.

Publications

Common genetic variation in the Estrogen Receptor Beta (ESR2) gene and osteoarthritis: results of a meta-analysis.

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