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

Borgquist, Signe LU ; Hjertberg, Maria ; Henningson, Maria LU ; Ingvar, Christian LU ; Rose, Carsten LU and Jernström, Helena LU (2013) In Breast Cancer Research and Treatment 137(3). p.849-862
Abstract
The role of estrogen receptor beta (ERβ) in breast cancer has been investigated since its identification in 1996. Studies based on protein expression have indicated that ERβ is a favorable prognostic marker. Further, ERβ expression is lower in obese breast cancer patients. 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... (More)
The role of estrogen receptor beta (ERβ) in breast cancer has been investigated since its identification in 1996. Studies based on protein expression have indicated that ERβ is a favorable prognostic marker. Further, ERβ expression is lower in obese breast cancer patients. 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 haplo- and 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. 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. (Less)
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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Breast Cancer Research and Treatment
volume
137
issue
3
pages
849 - 862
publisher
Springer
external identifiers
  • wos:000313944600019
  • pmid:23274843
  • scopus:84879388373
  • pmid:23274843
ISSN
1573-7217
DOI
10.1007/s10549-012-2367-z
language
English
LU publication?
yes
id
6acc801a-4648-4663-a2e4-2ee1ee235b4a (old id 3439152)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23274843?dopt=Abstract
date added to LUP
2016-04-01 13:35:30
date last changed
2022-03-21 19:24:55
@article{6acc801a-4648-4663-a2e4-2ee1ee235b4a,
  abstract     = {{The role of estrogen receptor beta (ERβ) in breast cancer has been investigated since its identification in 1996. Studies based on protein expression have indicated that ERβ is a favorable prognostic marker. Further, ERβ expression is lower in obese breast cancer patients. 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 haplo- and 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 &lt; 0.0001). Markedly impaired disease-free survival was found for genotypes in two out of four ESR2 htSNPs and for two haplotypes. 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.}},
  author       = {{Borgquist, Signe and Hjertberg, Maria and Henningson, Maria and Ingvar, Christian and Rose, Carsten and Jernström, Helena}},
  issn         = {{1573-7217}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{849--862}},
  publisher    = {{Springer}},
  series       = {{Breast Cancer Research and Treatment}},
  title        = {{Given breast cancer, is fat better than thin? Impact of the estrogen receptor beta gene polymorphisms.}},
  url          = {{https://lup.lub.lu.se/search/files/3464383/3559038.pdf}},
  doi          = {{10.1007/s10549-012-2367-z}},
  volume       = {{137}},
  year         = {{2013}},
}