Department of Breast Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Breast Cancer. 2019 Sep;26(5):562-572. doi: 10.1007/s12282-019-00956-5. Epub 2019 Feb 27.
Germinal center-associated nuclear protein (GANP) is a phosphoprotein involved in mRNA export and regulation of DNA recombination. Although GANP expression in human breast cancer tissue is associated with breast cancer prognosis, the association between the genetic background of GANP and susceptibility and prognosis of breast cancer is unclear.
We selected 694 breast cancer cases and 1376 age- and menopausal status-matched non-cancer controls from the Hospitable-based Epidemiologic Research Program, conducted at Aichi Cancer Center between 2001 and 2005. We evaluated the impact of two polymorphisms at the GANP locus (rs2839178 and rs11702450) on the susceptibility and prognosis of breast cancer. Reference alleles were defined as the A allele for rs2839178 and G allele for rs11702450.
The GG genotype of rs2839178 was statistically significantly associated with breast cancer risk (odds ratio [OR] 0.48, 95% confidence interval [CI] 0.30-0.76, P = 0.002). In prognostic analysis, compared to those with AA genotype of rs2839178, patients with AG or GG genotypes had longer disease-free survival (DFS) (hazard ratio [HR] 0.71, 95% CI 0.49-1.04 and HR 0.42, 95% CI 013-1.42, respectively, P for trend = 0.04). eQTL analysis indicated that association with rs2839178 can be explained by the effect of rs2839173 on expression of GANP/MCM3AP.
The G allele of rs2839178 at the GANP locus was significantly associated with reduced breast cancer risk and longer DFS in breast cancer patients, showing a consistent direction in the association between susceptibility and clinical outcome. GANP is, therefore, important for the occurrence and progression of sporadic breast cancer.
生发中心相关核蛋白（GANP）是一种参与 mRNA 输出和 DNA 重组调节的磷酸蛋白。尽管 GANP 在人乳腺癌组织中的表达与乳腺癌预后相关，但 GANP 基因背景与乳腺癌易感性和预后的关系尚不清楚。
我们从 2001 年至 2005 年在爱知县癌症中心进行的基于医院的流行病学研究计划中选择了 694 例乳腺癌病例和 1376 例年龄和绝经状态匹配的非癌症对照。我们评估了 GANP 基因座（rs2839178 和 rs11702450）的两个多态性对乳腺癌易感性和预后的影响。参考等位基因定义为 rs2839178 的 A 等位基因和 rs11702450 的 G 等位基因。
rs2839178 的 GG 基因型与乳腺癌风险呈统计学显著相关（优势比 [OR] 0.48，95%置信区间 [CI] 0.30-0.76，P=0.002）。在预后分析中，与 rs2839178 的 AA 基因型相比，rs2839178 的 AG 或 GG 基因型的患者无病生存时间（DFS）更长（风险比 [HR] 0.71，95%CI 0.49-1.04 和 HR 0.42，95%CI 0.13-1.42，P 趋势=0.04）。eQTL 分析表明，rs2839178 的关联可通过 rs2839173 对 GANP/MCM3AP 表达的影响来解释。
GANP 基因座 rs2839178 的 G 等位基因与乳腺癌风险降低和乳腺癌患者 DFS 延长显著相关，在易感性和临床结局之间的关联中表现出一致的方向。因此，GANP 对散发性乳腺癌的发生和发展很重要。
