Given breast cancer, is fat better than thin? Impact of the estrogen receptor beta gene polymorphisms

Abstract

Given breast cancer, is fat better than thin? Impact of the estrogen receptor beta gene polymorphisms.Borgquist, Signe; Hjertberg, Maria; Henningson, Maria; Ingvar, Christian; Rose, Carsten; Jernström, Helena Link to publication Citation for published version (APA): Borgquist, S., Hjertberg, M., Henningson, M., Ingvar, C., Rose, C., & Jernström, H. (2013). Given breast cancer, is fat better than thin? Impact of the estrogen receptor beta gene polymorphisms. Breast Cancer Research and Treatment, 137(3), 849-862. DOI: 10.1007/s10549-012-2367-z General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Fewer studies have focused on the prognostic impact of ERβ polymorphisms. Therefore, we analyzed the associations between four previously identified haplotype tagging single nucleotide polymorphisms (htSNPs), associated haplo-and diplotypes, and breast cancer-free survival according to body constitution.The patient cohort included 634 women from the prospective breast cancer and blood study (BC-Blood study, Sweden) with a median follow-up of 4.92 years. Four htSNPs (i.e., rs4986938, rs1256049, rs1256031, rs3020450) in the ESR2 gene and the correlating haploand diplotypes were analyzed and correlated to selected patient and tumor characteristics and to disease-free survival, including stratification for BMI. Based on the four htSNPs, seven haplotypes and eight diplotypes were identified. The patient and tumor characteristics were well-balanced across all geno-and haplotypes. Disease-free survival differed according to rs4986938 and rs1256031 (Log-Rank p=0.045 and p=0.041, respectively) and the number of haplotype copies of the wildtype CCGC and TCAC (Log-Rank p=0.027 and p=0.038, respectively). In the survival analyses stratified for BMI, significant survival differences between alleles were observed among overweight women (rs4986938 and rs1256031 with Log-Rank p=0.001 and p=0.001, respectively). The BMI-stratified survival analyses based on haplotypes showed shorter disease-free survival for overweight women with null copies of CCGC (Log-Rank p=0.001) and for overweight women with any TCAC copy (Log-Rank p<0.0001). Markedly impaired disease-free survival was found for genotypes in two out of four ESR2 htSNPs and for two haplotypes.3 ESR2 polymorphisms seem to divide patients into good and poor survivors based on BMI, stressing the need of taking host factors into consideration in the evaluation of prognostic markers.

Prognostic significance of body mass index in breast cancer patients with hormone receptor-positive tumours after curative surgery

“…Mousa et al [15] demonstrated that a lower BMI is associated with a shorter disease-free survival (DFS) in patients with early stage breast cancer. Similarly, Borgquist et al [16] showed that overweight may be protective in breast cancer patients with certain ERbeta genotypes.…”

High Estrogen Receptor β Expression Is Prognostic among Adjuvant Chemotherapy–Treated Patients—Results from a Population-Based Breast Cancer Cohort

“…Valid tumor ERb1 scores were obtained from 911 patients (88.8% 10 expression was not significantly associated with the four germline ERb htSNPs or the two haplotypes "any TCAC" or the number of CCGC, either overall or in patients with BMI !25 kg/m 2 , where two htSNPs and the two haplotypes were differently associated with DFS depending on BMI in our previous report (3).…”

“…Genotyping of the ESR2 htSNPs (rs4986938, rs1256031, rs1256049, and rs3020450) was performed, and haplotypes were constructed as described previously (3).…”

“…2). We have previously reported that ESR2 genotypes seem to divide patients into good and poor survivors, depending on the body mass index (BMI) of the patient (3). Whether ESR2 genotypes are associated with ERb tumor expression is currently unknown.…”

IL6 genotype, tumour ER-status, and treatment predicted disease-free survival in a prospective breast cancer cohort

“…IL-6 levels and body constitution are closely linked. Body constitution-related parameters, such as obesity, a high WHR, and a large breast volume, are associated with breast cancer prognosis [ 27 , 45 , 46 ]. This association is believed to be mediated by chronic inflammation [ 47 ].…”