Genetic Breast Cancer Susceptibility Variants and Prognosis in the Prospectively Randomized SUCCESS A Study

Hein A, Rack B, Li L, Ekici AB, Reis A, Lux MP, Cunningham JM, Rübner M, Fridley BL, Schneeweiss A, Tesch H, Lichtenegger W, Fehm T, Heinrich G, Rezai M, Beckmann M, Janni W, Weinshilboum RM, Wang L, Fasching P, Haeberle L (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Geburtshilfe und Frauenheilkunde Georg Thieme Verlag

Book Volume: 77

Pages Range: 651-659

Journal Issue: 6

DOI: 10.1055/s-0042-113189

Abstract

Large-scale genotyping studies have identified over 70 single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. However, knowledge regarding genetic risk factors associated with the prognosis is limited. The aim of this study was therefore to investigate the prognostic effect of nine known breast cancer risk SNPs. BC patients (n = 1687) randomly sampled in an adjuvant, randomized phase III trial (SUCCESS A study) were genotyped for nine BC risk SNPs: rs17468277 (CASP8) , rs2981582 (FGFR2) , rs13281615(8q24), rs3817198 (LSP1) , rs889312 (MAP3K1) , rs3803662 (TOX3) , rs13387042(2q35), rs4973768 (SLC4A7) , rs6504950 (COX11) . Cox proportional hazards models were used to test the SNPs' association with overall survival (OS) and progression-free survival (PFS). Additional analyses were carried out for molecular subgroups. rs3817198 in LSP1 (lymphocyte-specific protein 1) was the only SNP that significantly influenced OS (p = 0.01) and PFS (p < 0.01) in the likelihood ratio test comparing the genetic survival model with the clinical survival model. In the molecular subgroups, triple-negative patients with two minor alleles in rs3817198 had a much better prognosis relative to OS (adjusted HR 0.03; 95% CI 0.002 - 0.279) and PFS (HR 0.09; 95% CI 0.02 - 0.36) than patients with the common alleles. The same effect on PFS was shown for patients with luminal A tumors (HR 0.19; 95% CI 0.05 - 0.84), whereas patients with luminal B tumors had a poorer PFS with two minor alleles (HR 2.13; 95% CI 1.02 - 4.40). The variant in rs3817198 has a prognostic effect particularly in the subgroup of patients with triple-negative BC, suggesting a possible link with immunomodulation and BC.

Authors with CRIS profile

Alexander Hein Department of Obstetrics and Gynaecology Arif Bülent Ekici Institute of Human Genetics André Wiesmann da Silva Reis Lehrstuhl für Humangenetik Matthias Rübner Department of Obstetrics and Gynaecology Matthias Beckmann Lehrstuhl für Geburtshilfe und Frauenheilkunde Peter Fasching Professur für Translationale Frauenheilkunde und Geburtshilfe

Involved external institutions

Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Centrum für Hämatologie und Onkologie Bethanien DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) Universitätsklinikum Heidelberg DE Germany (DE) Onkologische Schwerpunktpraxis Bamberg DE Germany (DE) Mayo Clinic US United States (USA) (US) Universitätsklinikum Düsseldorf DE Germany (DE) Marien Hospital Düsseldorf DE Germany (DE) Universitätsklinikum Ulm DE Germany (DE)

How to cite

APA:

Hein, A., Rack, B., Li, L., Ekici, A.B., Reis, A., Lux, M.P.,... Haeberle, L. (2017). Genetic Breast Cancer Susceptibility Variants and Prognosis in the Prospectively Randomized SUCCESS A Study. Geburtshilfe und Frauenheilkunde, 77(6), 651-659. https://doi.org/10.1055/s-0042-113189

MLA:

Hein, Alexander, et al. "Genetic Breast Cancer Susceptibility Variants and Prognosis in the Prospectively Randomized SUCCESS A Study." Geburtshilfe und Frauenheilkunde 77.6 (2017): 651-659.

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