2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy

Nat Commun. 2014 Jun 17;5:4051. doi: 10.1038/ncomms5051.

Abstract

Large population-based registry studies have shown that breast cancer prognosis is inherited. Here we analyse single-nucleotide polymorphisms (SNPs) of genes implicated in human immunology and inflammation as candidates for prognostic markers of breast cancer survival involving 1,804 oestrogen receptor (ER)-negative patients treated with chemotherapy (279 events) from 14 European studies in a prior large-scale genotyping experiment, which is part of the Collaborative Oncological Gene-environment Study (COGS) initiative. We carry out replication using Asian COGS samples (n=522, 53 events) and the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) study (n=315, 108 events). Rs4458204_A near CCL20 (2q36.3) is found to be associated with breast cancer-specific death at a genome-wide significant level (n=2,641, 440 events, combined allelic hazard ratio (HR)=1.81 (1.49-2.19); P for trend=1.90 × 10(-9)). Such survival-associated variants can represent ideal targets for tailored therapeutics, and may also enhance our current prognostic prediction capabilities.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Chromosomes, Human, Pair 2 / genetics*
  • Drug Therapy / methods*
  • European Continental Ancestry Group / genetics
  • Female
  • Genetic Markers / genetics*
  • Humans
  • Kaplan-Meier Estimate
  • Linkage Disequilibrium
  • Polymorphism, Single Nucleotide / genetics
  • Prognosis
  • Proportional Hazards Models

Substances

  • Genetic Markers