Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Department of Pharmacy, Peking University People's Hospital, 100044, Beijing, China.
Int J Clin Oncol. 2019 May;24(5):476-484. doi: 10.1007/s10147-018-01386-7. Epub 2019 Jan 28.
Signal transducer and activator of transcription (STAT) 3 plays a vital role in carcinogenesis and drug response. Platinum-based chemotherapy is the first-line treatment for lung cancer patients, especially those in advanced stages. In the present study, we investigated the association of STAT3 polymorphism rs4796793 with lung cancer susceptibility, platinum-based chemotherapy response, and toxicity.
A total of 498 lung cancer patients and 213 healthy controls were enrolled in the study. 467 of them received at least 2-cycle platinum-based chemotherapy. Unconditional logistical regression analysis was used to assess the associations.
STAT3 rs4769793 G allele carriers had an increased susceptibility of lung cancer [additive model: adjusted OR (95% CI) 1.376 (1.058-1.789), P = 0.017; recessive model: adjusted OR (95% CI) 1.734 (1.007-2.985), P = 0.047]. Rs4769793 was not significantly associated with platinum-based chemotherapy response in lung cancer patients. STAT3 rs4796793 was associated with an increased risk of severe overall toxicity [additive model: adjusted OR (95% CI) 1.410 (1.076-1.850), P = 0.013; dominant model: adjusted OR (95% CI) 1.638 (1.091-2.459), P = 0.017], especially hematological toxicity [additive model: adjusted OR (95% CI) 1.352 (1.001-1.826), P = 0.049].
STAT3 rs4796793 may be considered as a potential candidate biomarker for the prediction of susceptibility and prognosis in Chinese lung cancer patients. However, well-designed studies with larger sample sizes are required to verify the results.
信号转导子和转录激活子 3(STAT3)在致癌作用和药物反应中起着至关重要的作用。基于铂的化疗是肺癌患者,特别是晚期患者的一线治疗方法。在本研究中,我们研究了 STAT3 多态性 rs4796793 与肺癌易感性、铂类化疗反应和毒性的关系。
共纳入 498 例肺癌患者和 213 例健康对照者。其中 467 例接受了至少 2 个周期的铂类化疗。采用非条件逻辑回归分析评估相关性。
STAT3 rs4769793 G 等位基因携带者肺癌易感性增加[加性模型:调整后的比值比(95%置信区间)1.376(1.058-1.789),P=0.017;隐性模型:调整后的比值比(95%置信区间)1.734(1.007-2.985),P=0.047]。rs4769793 与肺癌患者铂类化疗反应无显著相关性。STAT3 rs4796793 与严重总毒性风险增加相关[加性模型:调整后的比值比(95%置信区间)1.410(1.076-1.850),P=0.013;显性模型:调整后的比值比(95%置信区间)1.638(1.091-2.459),P=0.017],尤其是血液学毒性[加性模型:调整后的比值比(95%置信区间)1.352(1.001-1.826),P=0.049]。
STAT3 rs4796793 可作为中国肺癌患者易感性和预后预测的潜在候选生物标志物。然而,需要更大样本量的设计良好的研究来验证结果。