泰国乳腺癌患者中[具体基因]多态性对他莫昔芬及其代谢产物的影响。 （注：原文中“and”前后内容缺失，这里补充了“[具体基因]”以便使译文更完整通顺，实际翻译时需根据完整原文准确翻译）
Effects of and polymorphisms on tamoxifen and its metabolites in Thai breast cancer patients.
作者信息
Charoenchokthavee Wanaporn, Areepium Nutthada, Panomvana Duangchit, Sriuranpong Virote
机构信息
Department of Pharmacy Practice, Faculty of Pharmaceutical Science, Chulalongkorn University.
Medical Oncology Unit, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Pathumwan, Bangkok, Thailand.
出版信息
Breast Cancer (Dove Med Press). 2017 Apr 15;9:249-256. doi: 10.2147/BCTT.S125745. eCollection 2017.
PURPOSE
This study aimed to determine the effects of and polymorphisms on the levels of tamoxifen (TAM) and its metabolites in the plasma of breast cancer patients. The protocol was designed to test the associations between , genotypes and phenotypes (extensive metabolizer [EM], intermediate metabolizer [IM] and poor metabolizer [PM]) and TAM, -desmethyl tamoxifen (NDMT), endoxifen (END) and 4-hydroxytamoxifen (4OHT) concentrations.
PATIENTS AND METHODS
One hundred and thirty-four Thai breast cancer patients from the Thai Tamoxifen Project undergoing TAM treatment who met the inclusion/exclusion criteria were recruited. Plasma samples were assessed for the concentrations of TAM and its metabolites using high-performance liquid chromatography. The data are presented as actual values and metabolic ratios (MR). The hypotheses were tested using Kruskal-Wallis or Mann-Whitney test, including the simple main effects analysis.
RESULTS
The patients had stage 0-IV breast cancer. The mean age and body mass index were 51.6±11.6 years and 24.0±4.3, respectively. Also, 53.0% of them were premenopausal, 10.4% were perimenopausal and 36.6% were postmenopausal, while 23.1% were -EM/-EM and 20.9% carried only and incomplete alleles. The median concentrations of TAM, NDMT, END and 4OHT were 374.7 (interquartile range [IQR] 230.2) ng/mL, 1,064.9 (IQR 599.6) ng/mL, 54.5 (IQR 52.5) ng/mL and 5.0 (IQR 3.1) ng/mL, respectively. MR (TAM-NDMT) and MR (NDMT-END) were statistically different (=0.013 and =0.014, respectively), while MR (4OHT-END) was not statistically different within the phenotype (=0.594). MR (TAM-4OHT) was not statistically different within the phenotype (=0.079), but it was potentially different from -PM (=0.056). None of the MR was statistically different within the phenotype.
CONCLUSION
polymorphisms appear to affect END concentration through an NDMT subpathway and potentially affect 4OHT concentrations through a 4OHT subpathway in -PM group.
目的
本研究旨在确定[基因名称1]和[基因名称2]多态性对乳腺癌患者血浆中他莫昔芬（TAM）及其代谢产物水平的影响。该方案旨在测试[基因名称1]、[基因名称2]基因型和表型（广泛代谢型[EM]、中间代谢型[IM]和慢代谢型[PM]）与TAM、N-去甲基他莫昔芬（NDMT）、内昔芬（END）和4-羟基他莫昔芬（4OHT）浓度之间的关联。
患者与方法
招募了134名来自泰国他莫昔芬项目且正在接受TAM治疗并符合纳入/排除标准的泰国乳腺癌患者。使用高效液相色谱法评估血浆样本中TAM及其代谢产物的浓度。数据以实际值和代谢比（MR）表示。使用Kruskal-Wallis或Mann-Whitney U检验对假设进行检验，包括简单主效应分析。
结果
患者患有0-IV期乳腺癌。平均年龄和体重指数分别为51.6±11.6岁和24.0±4.3。此外，53.0%为绝经前，10.4%为围绝经期，36.6%为绝经后，而23.1%为[基因名称1]-EM/-EM，20.9%仅携带[基因名称1]和[基因名称2]的不完全等位基因。TAM、NDMT、END和4OHT的中位浓度分别为374.7（四分位间距[IQR] 230.2）ng/mL、1064.9（IQR 599.6）ng/mL、54.5（IQR 52.5）ng/mL和5.0（IQR 3.1）ng/mL。MR（TAM-NDMT）和MR（NDMT-END）在统计学上有差异（分别为P = 0.013和P = 0.014），而在[基因名称1]表型内MR（4OHT-END）无统计学差异（P = 0.594）。在[基因名称2]表型内MR（TAM-4OHT）无统计学差异（P = 0.079），但与[基因名称2]-PM可能不同（P = 0.056）。在[基因名称3]表型内，所有MR均无统计学差异。
结论
在[基因名称2]-PM组中，[基因名称2]多态性似乎通过NDMT子途径影响END浓度，并可能通过4OHT子途径影响4OHT浓度。
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