Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Carcinogenesis. 2013 Mar;34(3):587-94. doi: 10.1093/carcin/bgs369. Epub 2012 Nov 24.
Epidemiological studies have investigated the association between vitamin D pathway genes and breast cancer risk; however, little is known about the association between vitamin D pathway genes and breast cancer prognosis. In a retrospective cohort of 1029 patients with early-stage breast cancer, we analyzed the association between 106 tagging single nucleotide polymorphisms (SNPs) in eight vitamin D pathway genes and breast cancer disease-free survival (DFS) using Cox regression analysis adjusted for known prognostic variables. Using a false discovery rate of 10%, six intronic SNPs were significantly associated with poorer DFS: retinoid-X receptor alpha (RXRA) SNPs (rs881658, rs11185659, rs10881583, rs881657 and rs7864987) and plasminogen activator and urokinase receptor (PLAUR) SNP (rs4251864). Treatment received (no systemic therapy, hormone therapy alone or chemotherapy) was an effect modifier of the RXRA SNPs association with DFS (P < 0.05); therefore, we stratified further analysis by treatment group. Among patients who did not receive systemic therapy, RXRA SNP [rs10881583 (P = 0.02)] was associated with poorer DFS, and among patients who received chemotherapy, RXRA SNPs (rs881658, rs11185659, rs10881583, rs881657 and rs7864987) were associated with poorer DFS (P < 0.001 for all SNPs). However, RXRA SNPs: rs10881583 (P < 0.001) and rs881657 (P = 0.02) were associated with improved DFS in patients treated with hormone therapy alone. Our results suggest that SNPs in the RXRA and PLAUR genes in the vitamin D pathway may contribute to breast cancer DFS. In particular, SNPs in RXRA may predict for poorer or improved DFS in patients, according to type of systemic treatment received. If validated, these markers could be used for risk stratification of breast cancer patients.
流行病学研究已经调查了维生素 D 途径基因与乳腺癌风险之间的关联;然而,关于维生素 D 途径基因与乳腺癌预后之间的关联知之甚少。在一项对 1029 例早期乳腺癌患者的回顾性队列研究中,我们使用 Cox 回归分析调整了已知的预后变量,分析了 8 个维生素 D 途径基因中的 106 个标记单核苷酸多态性 (SNP) 与乳腺癌无病生存 (DFS) 之间的关系。使用 10%的错误发现率,6 个内含子 SNP 与较差的 DFS 显著相关:视黄醇 X 受体 alpha (RXRA) SNP(rs881658、rs11185659、rs10881583、rs881657 和 rs7864987) 和纤溶酶原激活物和尿激酶受体 (PLAUR) SNP(rs4251864)。所接受的治疗(无全身治疗、单独激素治疗或化疗)是 RXRA SNP 与 DFS 相关性的效应修饰因子(P < 0.05);因此,我们根据治疗组进一步分层分析。在未接受全身治疗的患者中,RXRA SNP(rs10881583,P = 0.02)与较差的 DFS 相关,而在接受化疗的患者中,RXRA SNPs(rs881658、rs11185659、rs10881583、rs881657 和 rs7864987)与较差的 DFS 相关(P < 0.001 所有 SNP)。然而,RXRA SNP(rs10881583,P < 0.001)和 rs881657(P = 0.02)与单独接受激素治疗的患者的 DFS 改善相关。我们的研究结果表明,维生素 D 途径中的 RXRA 和 PLAUR 基因中的 SNP 可能与乳腺癌 DFS 有关。特别是,RXRA 中的 SNP 可能根据所接受的全身治疗类型预测患者的较差或较好的 DFS。如果得到验证,这些标志物可用于乳腺癌患者的风险分层。