Abstract 820: Molecular epidemiological studies of germinal center-associated nuclear protein (ganp) in the development of human sporadic breast cancers

Abstract

Abstract [Introduction] The altered expression of germinal center-associated nuclear protein (GANP), a member of mammalian TREX2 complex, has been observed in various tumors. Previously, we demonstrated that deficiency of GANP developed mammary gland tumors resembling human breast cancers in two mouse models. In addition, we showed that decreased expression of GANP was an independent prognostic factor of human breast cancer in a retrospective cohort study. These results suggested that GANP might be associated with breast cancer development. Although a little is know about functional significance of ganp polymorphisms, we explored possible association. [Methods] We conducted a case-control study to examine association between ganp polymorphisms and risk of breast cancer among Japanese population within the framework of the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC). Cases are 694 incident cases who had been diagnosed as breast cancer at Aichi Cancer Center Hospital (ACCH) during 2001-2005. A total of 1,376 non-cancer controls were patients who visited ACCH at same period as cases and were confirmed to have no evidence of cancer. Controls were individually matched for age and menopausal status with cases. ganp polymorphisms were assessed by iCOGS chip (Reference: Michailidou K et al. Nat. Genet. 2013;45:353-361). Multivariable conditional logistic regression models were applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for each locus. [Results] Ten out of 13 polymorphisms, in high linkage disequilibrium, showed statistically significant associations with breast cancer risk. For instance, in rs2839186, the OR for those with AA alleles compared with those with GG alleles is 0.41 (95% CI, 0.23-0.72, p = 0.002) in genotype model. As compared with those with G allele, the OR for those without was 0.40 (95% CI, 0.23-0.71, p = 0.002) in recessive model. On the other hand, in dominant model, the OR for those with A allele was 0.95 (95% CI, 0.78-1.16, p = 0.635) in comparison to those without that. [Conclusion] In this study, we clearly show that mutant SNPs in rs2839186 decrease breast cancer risk. We are currently analyzing if the ganp SNPs affect the prognosis of breast cancer patients. Citation Format: Kazuhiko Kuwahara, Hidemi Ito, Kiyotaka Kuzushima, Hiroji Iwata, Hideo Tanaka, Keitaro Matsuo. Molecular epidemiological studies of germinal center-associated nuclear protein (ganp) in the development of human sporadic breast cancers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 820.