Abstract P5-09-07: Impact of germinalcenter-associated nuclear protein polymorphisms on breast cancer risk and prognosis in a Japanese population

Abstract

Abstract Background: Germinal center-associated nuclear protein (GANP) is a phosphoprotein which is involved in mRNA export and the regulation of DNA recombination. We have previously demonstrated that deficiency of GANP led to spontaneous development of mammary gland tumors in a mouse model. In addition, we found that decreased GANP expression in human breast cancer tissue was an independent prognostic factor. Here, we conducted a case-control study and a retrospective cohort study to investigate whether single nucleotide polymorphisms (SNPs) of GANP are associated with sporadic breast cancer risk and prognosis in a Japanese population. Subjects and Methods: Six hundred-ninety-four breast cancer cases and 1,376 age- and menopausal status-matched controls were selected within the framework of the Hospital-based Epidemiologic Research Program at Aichi Cancer Center. Cases and controls were genotyped using an Infinium iSelect custom array (iCOGS, Illumina Inc., San Diego, CA, USA). We assessed 13 SNPs at the GANP locus, 2 SNPs (rs2839178 and rs11702450) were selected for further analysis by considering linkage disequilibrium. Conditional logistic regression methods were used to estimate odds ratios (ORs) and 95% confidence intervals. In addition, the survival impact of the two SNPs was retrospectively analyzed using the 694 breast cancer cases. To evaluate the effect of SNPs on overall survival (OS) and disease-free survival (DFS), multivariate Cox proportional hazards modeling was applied. Results: Compared to the AA genotype of rs2839178, the GG genotype showed statistically significant associations with breast cancer risk (OR: 0.48, 95%CI:0.30–0.76, P = 0.002). In prognostic analysis, compared to those with the genotype AA at rs2839178, patients with AG or GG showed longer DFS (HR: 0.71, 95%CI: 0.49–1.04 and 0.42, 0.13–1.42, respectively, P for trend = 0.04). The GG genotype of rs2839178 also showed a positive tendency for longer OS although it was not statistically significant (HR: 0.69, 95%CI: 0.44–1.08, P = 0.11). We did not find that rs11702450 was associated with either breast cancer risk or prognosis. Conclusion: This is the first study to investigate the association between GANP SNPs and breast cancer risk and prognosis. The direction of association with DFS was consistent with that of susceptibility. These results demonstrate that GANP SNPs presumably prevent the occurrence and malignant advancement of sporadic breast cancers. Citation Format: Kotani H, Ito H, Kuwahara K, Kuzushima K, Iwata H, Tsunoda N, Nagino M, Tanaka H, Matsuo K. Impact of germinalcenter-associated nuclear protein polymorphisms on breast cancer risk and prognosis in a Japanese population [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-09-07.