Objective: 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. Methods: 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 genotype classified under a dominant genetic model, we used rank sum tests to identify ESR2 SNPs significantly associated (p < 0.05) with ERβ expression. Results: 35%, 35%, and 29% of lung tumors showed no/low (Allred < 6), intermediate (Allred 6-7), and maximal (Allred 8) cytoplasmic ERβ expression, whereas 13%, 27%, and 60% showed no/low, intermediate, and maximal nuclear ERβ expression. For SNPs rs8021944, rs1256061 and rs10146204, ERβ 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) ERβ 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 ERβ lung tumor expression.
Bibliographical noteFunding Information:
This work was supported by National Institutes of Health grants P50 CA090440 , R25 CA057703 , and P30 CA047904 . Study sponsors did not play any role in the study design, in the collection, analysis or interpretation of data, in the writing of the manuscript, or in the decision to submit the manuscript for publication.
- Estrogen receptor
- Genetic polymorphism
- Lung cancer