Relationship of ZNF423 and CTSO with breast cancer risk in two randomised tamoxifen prevention trials

Research output: Contribution to journalArticlepeer-review

  • External authors:
  • Adam R. Brentnall
  • Jack Cuzick
  • Corrinne Segal
  • Caroline Reuter
  • Simone Detre
  • Ivana Sestak
  • Trevor J. Powles
  • Mitchell Dowsett

Abstract

A case–control study from two randomised breast cancer prevention trials of tamoxifen and raloxifene (P-1 and P-2) identified single-nucleotide polymorphisms (SNPs) in or near genes ZNF423 and CTSO as factors which predict which women will derive most anti-cancer benefit from selective oestrogen receptor modulator (SERM) therapy. In this article, we further examine this question using blood samples from two randomised tamoxifen prevention trials: the International Breast Cancer Intervention Study I (IBIS-I) and the Royal Marsden trial (Marsden). A nested case–control study was designed with 2:1 matching in IBIS-I and 1:1 matching in Marsden. The OncoArray was used for genotyping and included two SNPs previously identified (rs8060157 in ZNF423 and rs10030044 near CTSO), and 102 further SNPs within the same regions. Overall, there were 369 cases and 662 controls, with 148 cases and 268 controls from the tamoxifen arms. Odds ratios were estimated by conditional logistic regression, with Wald 95 % confidence intervals. In the tamoxifen arms, the per-allele odds ratio for rs8060157 was 0.99 (95 %CI 0.73–1.34) and 1.00 (95 %CI 0.76–1.33) for rs10030044. In the placebo arm, the odds ratio was 1.10 (95 %CI 0.87–1.40) for rs8060157 and 1.01 (95 %CI 0.79–1.29) for rs10030044. There was no evidence to suggest that other SNPs in the surrounding regions of these SNPs might predict response to tamoxifen. Results from these two prevention trials do not support the earlier findings. rs8060157 in ZNF423 and rs10030044 near CTSO do not appear to predict response to tamoxifen.

Bibliographical metadata

Original languageEnglish
Pages (from-to)591-596
Number of pages6
JournalBreast Cancer Research and Treatment
Volume158
Issue number3
Early online date11 Jul 2016
DOIs
Publication statusPublished - 1 Aug 2016