Dataset Information

Genetic variation in ESR2 and estrogen receptor-beta expression in lung tumors.

ABSTRACT:

Objective

To investigate the association between inherited variation in the estrogen receptor beta (ER?) gene (ESR2) and ER? lung tumor expression, a phenotype that possibly affects survival differently in men and women.

Methods

We genotyped 135 lung cancer patients for 22 ESR2 single nucleotide polymorphisms (SNPs) and measured nuclear and cytoplasmic ER? expression by immunohistochemistry (IHC) in their primary lung tumor. Distributing Allred ER? IHC scores according to ESR2 genotype classified under a dominant genetic model, we used rank sum tests to identify ESR2 SNPs significantly associated (p<0.05) with ER? expression.

Results

35%, 35%, and 29% of lung tumors showed no/low (Allred<6), intermediate (Allred 6-7), and maximal (Allred 8) cytoplasmic ER? expression, whereas 13%, 27%, and 60% showed no/low, intermediate, and maximal nuclear ER? expression. For SNPs rs8021944, rs1256061 and rs10146204, ER? expression was higher according to the rank sum test in lung tumors from patients with at least one minor allele. For each of these three SNPs, the odds of maximal (Allred 8) relative to no/low (Allred<6) ER? expression was 3-fold higher in tumors from patients with at least one minor allele than in tumors from patients homozygous for the common allele.

Conclusion

Inherited variability in ESR2 may determine ER? lung tumor expression.

SUBMITTER: Song JY

PROVIDER: S-EPMC3684046 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Publications

Genetic variation in ESR2 and estrogen receptor-beta expression in lung tumors.

Song Ji Young JY Siegfried Jill M JM Diergaarde Brenda B Land Stephanie R SR Bowser Robert R Stabile Laura P LP Dacic Sanja S Dhir Rajiv R Nukui Tomoko T Romkes Marjorie M Weissfeld Joel L JL

Cancer epidemiology 20130423 4

<h4>Objective</h4>To investigate the association between inherited variation in the estrogen receptor beta (ERβ) gene (ESR2) and ERβ lung tumor expression, a phenotype that possibly affects survival differently in men and women.<h4>Methods</h4>We genotyped 135 lung cancer patients for 22 ESR2 single nucleotide polymorphisms (SNPs) and measured nuclear and cytoplasmic ERβ expression by immunohistochemistry (IHC) in their primary lung tumor. Distributing Allred ERβ IHC scores according to ESR2 gen ...[more]

PMID: 23619141

Similar Datasets

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

Genetic variation in ESR2 and estrogen receptor-beta expression in lung tumors.

Objective

Methods

Results

Conclusion

Publications

Genetic variation in ESR2 and estrogen receptor-beta expression in lung tumors.

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