Department of Medicine, Health Sciences Center, Londrina State University, Londrina, Parana, Brazil.
Department of Clinical Research, Londrina Cancer Hospital, Londrina, Parana, Brazil.
Clin Exp Med. 2018 Feb;18(1):27-35. doi: 10.1007/s10238-017-0461-6. Epub 2017 Apr 28.
Breast cancer (BC) is the main worldwide neoplasia in women. The metabolic balance between xenobiotic absorption and elimination rates plays an important role in preventing DNA damage and, consequently, tumor development. The glutathione S-transferases (GSTs), such as GSTM1 and GSTT1, and the NAD(P)H quinone oxidoreductase are important enzymes involved in phase II detoxification reactions. Deletions in GSTM1 and GSTT1, and single-nucleotide polymorphism (SNP) in NQO1 (rs1800655) have been investigated in cancer context, revealing conflicting results. The present study analyzed these genetic polymorphisms in 121 BC patients and 151 BC-free controls in order to verify if they could act as susceptibility modifiers and/or prognostic factors. Binary logistic regressions adjusted by age were performed to assess associations between allelic variants and interactions in polymorphisms combination with BC susceptibility, but no significant association was found. Genotypes distribution was also compared between BC subtypes, but no significant difference was observed (p > 0.05). GSTM1 deletion was significantly associated with histopathological grade, with a greater proportion of patients presenting grade III tumors (p = 0.007). Univariate analysis identified tumor size as the only clinicopathological parameter potentially associated with recurrence risk in patients that received adjuvant chemotherapy (p < 0.1). Thus, logistic regression analysis adjusted by tumor size revealed a positive association between GSTT1 deletion and recurrence risk in general BC (OR 4.25; p = 0.04), while GSTM1 was negatively associated with recurrence risk in ER/PRHER2 samples (OR 0.07; p = 0.03). In conclusion, the present study indicated that GSTT1 deletion was associated with increased recurrence risk, while GSTM1 correlated with worst prognosis parameters at diagnosis, but was negatively associated with recurrence risk in luminal subtype samples.
乳腺癌（BC）是全球女性中主要的肿瘤疾病。外源性物质吸收和消除速率之间的代谢平衡在防止 DNA 损伤以及肿瘤发生方面起着重要作用。谷胱甘肽 S-转移酶（GSTs），如 GSTM1 和 GSTT1，以及 NAD（P）H 醌氧化还原酶，是参与 II 相解毒反应的重要酶。GSTM1 和 GSTT1 的缺失以及 NQO1（rs1800655）的单核苷酸多态性（SNP）已在癌症背景下进行了研究，结果存在矛盾。本研究分析了 121 例 BC 患者和 151 例无 BC 对照组中的这些遗传多态性，以验证它们是否可以作为易感性修饰因子和/或预后因素。通过年龄调整的二元逻辑回归来评估等位基因变体与多态性组合与 BC 易感性之间的关联和相互作用，但未发现显著相关性。还比较了 BC 亚型之间的基因型分布，但未观察到显著差异（p＞0.05）。GSTM1 缺失与组织病理学分级显著相关，存在更多 III 级肿瘤的患者（p=0.007）。单变量分析确定肿瘤大小是接受辅助化疗的患者复发风险的唯一临床病理参数（p＜0.1）。因此，通过肿瘤大小调整的逻辑回归分析表明，GSTT1 缺失与一般 BC 的复发风险呈正相关（OR 4.25；p=0.04），而 GSTM1 与 ER/PRHER2 样本的复发风险呈负相关（OR 0.07；p=0.03）。总之，本研究表明 GSTT1 缺失与复发风险增加相关，而 GSTM1 与诊断时的预后不良参数相关，但与 luminal 亚型样本的复发风险呈负相关。
