Data from Diverse Associations between <i>ESR1</i> Polymorphism and Breast Cancer Development and Progression

Abstract

<div>Abstract<p><b>Purpose:</b> To test the hypothesis that polymorphisms of <i>ESR1</i>, the gene encoding estrogen receptor α (ERα), are associated with susceptibility, clinical phenotype, and progression of breast cancer.</p><p><b>Patients and Methods:</b> A case-control study was done on 940 patients with incident breast cancer and 1,547 healthy female controls. Fifteen single-nucleotide polymorphisms (SNP) selected from chr6:152,170,379-152,466,100 (exons 1–8 of the <i>ESR1</i> gene, excluding flanking sequences), reflecting major polymorphisms of this gene, were genotyped. Frequencies of SNPs were compared between cases and controls to identify SNPs associated with cancer susceptibility and between cases with different clinical phenotypes to determine the role of <i>ESR1</i> polymorphism in cancer progression.</p><p><b>Results:</b> SNPs located in one cluster in intron 1 and one haplotype, based on these SNPs, showed a significant association with breast cancer susceptibility. The tumorigenic contribution of these intron 1 SNPs was more obvious in combination with reproductive risk factors (<i>P</i> for interaction <0.05). One of these intron 1 SNPs was also significantly associated with low ERα expression in tumors. Interestingly, the same intron 1 SNPs showed a correlation with worse clinical phenotypes, including poor differentiation of tumor cells and a late stage. These intron 1 SNPs also showed a significant association with the 5-year breast cancer–specific survival rate of patients, but had opposite effects in ERα-negative and ERα-positive early-stage patients.</p><p><b>Conclusions:</b> Our findings provide support for diverse roles of <i>ESR1</i> polymorphism in determining susceptibility in different stages of breast cancer. The differences between the important <i>ESR1</i> SNPs identified in Chinese women in this study and those identified in studies on Western women with breast cancer suggest different roles of ERα in these two populations. Clin Cancer Res; 16(13); 3473–84. ©2010 AACR.</p></div>