title: Relationship of ZNF423 and CTSO with breast cancer risk in two randomised tamoxifen prevention trials.
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.
authors.affiliation: Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, Charterhouse Square, London, EC1M 6BQ, UK.
authors.forename: Adam R
authors.initials: AR
authors.lastname: Brentnall
authors.affiliation: Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, Charterhouse Square, London, EC1M 6BQ, UK. j.cuzick@qmul.ac.uk.
authors.forename: Jack
authors.initials: J
authors.lastname: Cuzick
authors.affiliation: Manchester Centre for Genomic Medicine, University of Manchester and Central Manchester Foundation Trust, Manchester, M13 9WL, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Byers
authors.affiliation: Royal Marsden Hospital, London, SW3 6JJ, UK.|The Institute of Cancer Research, London, SW7 3RP, UK.
authors.forename: Corrinne
authors.initials: C
authors.lastname: Segal
authors.affiliation: Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, Charterhouse Square, London, EC1M 6BQ, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Reuter
authors.affiliation: Royal Marsden Hospital, London, SW3 6JJ, UK.
authors.forename: Simone
authors.initials: S
authors.lastname: Detre
authors.affiliation: Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, Charterhouse Square, London, EC1M 6BQ, UK.
authors.forename: Ivana
authors.initials: I
authors.lastname: Sestak
authors.affiliation: The Christie NHS Foundation Trust, Manchester, M20 4BX, UK.
authors.forename: Anthony
authors.initials: A
authors.lastname: Howell
authors.affiliation: Cancer Centre London, London, SW19 5NB, UK.
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Powles
authors.affiliation: Manchester Centre for Genomic Medicine, University of Manchester and Central Manchester Foundation Trust, Manchester, M13 9WL, UK.
authors.forename: William G
authors.initials: WG
authors.lastname: Newman
authors.affiliation: Royal Marsden Hospital, London, SW3 6JJ, UK.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Dowsett
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000235:genetics / Q000517:prevention & control*; D016022:Case-Control Studies; D002403:Cathepsins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011506:Proteins; D016032:Randomized Controlled Trials as Topic; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004268:DNA-Binding Proteins; D011506:Proteins; C031017:ornithine decarboxylase antizyme; D013629:Tamoxifen; D002403:Cathepsins; C534179:CTSO protein, human
keywords: Breast cancer; Randomised prevention trials; Single-nucleotide polymorphisms; Stratified medicine; Tamoxifen response