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

  • Epidemiology
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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 < 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.

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Acknowledgments

We want to thank all the participants in this study. We also wish to thank the following research nurses for their work in the data collection: Annette Möller, Karin Henriksson, Anna Weddig, Linda Ågren, and Maj-Britt Hedenblad. We would like to acknowledge Sol-Britt Olsson, Erika Bågeman, Anita Schmidt Casslén, and Kristina Lövgren for handling the blood samples and the DNA extraction.

Conflicts of interest

The authors declare that they have no conflict of interest.

Funding

Funding for this study was provided by grants from the Swedish Cancer Society, the Swedish Research Council, the Mrs. Berta Kamprad Cancer Foundation, Lund University Hospital Fund, the Gunnar Nilsson Foundation, the Konung Gustav V:s Jubileumsfond, the GA’s Donation for Breast Cancer Research, the 1049 Fund at the Lund Oncology Clinic, the Region Skåne ALF, the Medical Faculty of Lund University, and BRO.

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Authors and Affiliations

  1. Department of Oncology, Clinical Sciences, Skåne University Hospital, Lund University, 221 85, Lund, Sweden

    Signe Borgquist, Maria Hjertberg, Maria Henningson, Carsten Rose & Helena Jernström

  2. Department of Surgery, Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden

    Christian Ingvar

  3. Division of Cancer and Hematology, Skåne University Hospital, Lund, Sweden

    Carsten Rose

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  1. Signe Borgquist
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Correspondence to Signe Borgquist.

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Borgquist, S., Hjertberg, M., Henningson, M. et al. Given breast cancer, is fat better than thin? Impact of the estrogen receptor beta gene polymorphisms. Breast Cancer Res Treat 137, 849–862 (2013). https://doi.org/10.1007/s10549-012-2367-z

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