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

Objective: To investigate the association between inherited variation in the estrogen receptor beta (ER beta) gene (ESR2) and ER beta 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 beta expression by immunohistochemistry (IHC) in their primary lung tumor. Distributing Allred ER beta 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 beta expression. Results: 35%, 35%, and 29% of lung tumors showed no/low (Allred < 6), intermediate (Allred 6-7), and maximal (Allred 8) cytoplasmic ER beta expression, whereas 13%, 27%, and 60% showed no/low, intermediate, and maximal nuclear ER beta expression. For SNPs rs8021944, rs1256061 and rs10146204, ER beta 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 beta 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 beta lung tumor expression. (C) 2013 Elsevier Ltd. All rights reserved.