Relationship of ZNF423 and CTSO with breast cancer risk in two randomised tamoxifen prevention trials.
Authors
Brentnall, ACuzick, J
Byers, H
Segal, C
Reuter, C
Detre, S
Sestak, I
Howell, Anthony
Powles, T
Newman, W
Dowsett, M
Affiliation
Centre for Cancer Prevention, Wolfson Institute of Preventive MedicineIssue Date
2016-08
Metadata
Show full item recordAbstract
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.Citation
Relationship of ZNF423 and CTSO with breast cancer risk in two randomised tamoxifen prevention trials. 2016, 158 (3):591-6 Breast Cancer Res. Treat.Journal
Breast Cancer Research and TreatmentDOI
10.1007/s10549-016-3885-xPubMed ID
27400912Type
ArticleLanguage
enISSN
1573-7217ae974a485f413a2113503eed53cd6c53
10.1007/s10549-016-3885-x