Abstract P5-05-02: Prognostic impact of single-nucleotide polymorphisms (SNPs) in or near the ZNF423 and CTSO genes in estrogen receptor (ER)-positive breast cancer patients receiving adjuvant endocrine therapy

Abstract

Abstract Background: Selective estrogen receptor modulators (SERMs) can reduce the occurrence of breast cancer in high-risk women by 50%. Recently, a genome-wide association study identified SNPs in or near the ZNF423 (rs8060157) and CTSO (rs10030044) genes that were associated with breast cancer risk during SERM therapy and these SNPs were reported to be involved in estrogen-dependent induction of BRCA1 expression (Ingle JN. et al. Cancer Discovery 2013). Materials and methods: A total of 588 breast carcinomas collected between 1983 and 2003 were available for polymorphism assay. TaqMan pre-designed SNP genotyping assays for ZNF423 rs8060157 and CTSO rs10030044 were used. We investigated whether these SNPs are associated with prognosis in breast cancer patients. The effects of several variables on survival were tested by Cox proportional hazards regression analysis. Results: Estrogen receptor (ER)-positive breast cancer patients receiving adjuvant endocrine therapy with the genotype GG at CTSO rs10030044 showed significantly shorter disease-free survival (DFS) and overall survival (OS) (P = 0.0024 and P = 0.0003, respectively). On the other hand, this genotype were not associated with prognosis in ER-negative breast cancer patients. Multivariate Cox regression analysis revealed that the GG genotype at CTSO rs10030044 was an independent poor prognostic factor in ER-positive breast cancer patients receiving adjuvant endocrine therapy (OS: RR = 1.86; 95%CI, 1.18 to 2.85). Univariate and multivariate Cox regression analysis of factors associated with overall survival Variablesn (%)Univariate (P value)Multivariate (P value)Multivariate (RR :95% CI)tumor size≤2cm210 (36) 1 (reference) >2cm376 (64)<.0001<.00012.268 (1.615-3.181)Nodal statusNegative369 (63) 1 (reference) Positive216 (37)<.0001<.00013.117 (1.984-4.954)Grade1,2426 (72) 1 (reference) 3123 (21)0.00010.9700.994 (0.731-1.356)ER atatusPositive440 (75) 1 (reference) Negative145 (25)<.00010.0691.666 (0.962-2.893)PR statusPositive377 (64) 1 (reference) Negative208 (35)0.00050.2241.399 (0.812-2.380)HER2 statusPositive55 (9) 1 (reference) Negative324 (55)<.00010.00080.420 (0.261-0.690)rs10030044TT+GT479 (81) 1 (reference) GG109 (19)0.02820.00821,860 (1.181-2.853) The SNP, ZNF423 rs8060157, was not associated with prognosis in this study. Conclusion: We show that the genotype GG at CTSO rs10030044 is an independent factor indicating poor prognosis in ER-positive breast cancer patients receiving adjuvant endocrine therapy. Citation Format: Yukari Hato, Yumi Endo, Nobuyasu Yoshimoto, Tomoko Asano, Mina Yamaguchi, Satoru Takahashi, Tatsuya Toyama. Prognostic impact of single-nucleotide polymorphisms (SNPs) in or near the ZNF423 and CTSO genes in estrogen receptor (ER)-positive breast cancer patients receiving adjuvant endocrine therapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-05-02.