Hu Lei, Chen Shu-Hui, Lv Qiao-Li, Sun Bao, Qu Qiang, Qin Chong-Zhen, Fan Lan, Guo Ying, Cheng Lin, Zhou Hong-Hao
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China.
Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China.
Int J Environ Res Public Health. 2016 May 30;13(6):545. doi: 10.3390/ijerph13060545.
Long non-coding RNA (lncRNA) CASC8 rs10505477 polymorphism has been identified to be related to risk of many kinds of cancers, such as colorectal cancer, gastric cancer, and invasive ovarian cancer, and it may be involved in the prognosis of gastric cancer patients who have received platinum-based chemotherapy after surgical treatment. So far, there is no study investigating the clinical significance of lncRNA CASC8 rs10505477 in lung cancer susceptibility and treatment. In this study, we genotyped 498 lung cancer patients and 213 healthy control subjects to explore the correlation between the rs10505477 polymorphism and lung cancer risk in a Chinese population. Among the 498 patients, 467 were selected for the chemotherapy response and toxicity study. We found that the single nucleotide polymorphisms (SNP) rs10505477 was greatly related to lung cancer risk in male and adenocarcinoma subgroups in recessive model (adjusted OR = 0.51, 95%CI = 0.29-0.90, p = 0.02; adjusted OR = 0.52, 95%CI = 0.30-0.89, p = 0.02, respectively). It was also closely correlated with platinum-based chemotherapy response in dominant model (adjusted OR = 1.58, 95%CI = 1.05-2.39, p = 0.03). Additionally, we observed that CASC8 rs10505477 polymorphism was significantly relevant to severe hematologic toxicity in non-small-cell lung cancer (NSCLC) subgroup in dominant model (adjusted OR = 0.59, 95%CI = 0.35-0.98, p = 0.04) and in additive model (adjusted OR = 0.62, 95%CI = 0.43-0.90, p = 0.01). Furthermore, it was found that rs10505477 polymorphism was greatly associated with gastrointestinal toxicity in SCLC and cisplatin subgroups in dominant model (adjusted OR = 7.82, 95%CI = 1.36-45.07, p = 0.02; adjusted OR = 1.94, 95%CI = 1.07-3.53, p = 0.03, respectively). Thus, lncRNA CASC8 rs10505477 could serve as a possible risk marker for diagnosing lung cancer, and could be used to forecast the response and toxicity of platinum-based treatment in lung cancer patients.
长链非编码RNA（lncRNA）CASC8 rs10505477多态性已被证实与多种癌症的风险相关，如结直肠癌、胃癌和侵袭性卵巢癌，并且它可能参与了接受手术治疗后铂类化疗的胃癌患者的预后。到目前为止，尚无研究探讨lncRNA CASC8 rs10505477在肺癌易感性和治疗中的临床意义。在本研究中，我们对498例肺癌患者和213例健康对照者进行基因分型，以探讨rs10505477多态性与中国人群肺癌风险之间的相关性。在498例患者中，选取467例进行化疗反应和毒性研究。我们发现，单核苷酸多态性（SNP）rs10505477在隐性模型中与男性和腺癌亚组的肺癌风险密切相关（调整后的OR = 0.51，95%CI = 0.29 - 0.90，p = 0.02；调整后的OR = 0.52，95%CI = 0.30 - 0.89，p = 0.02）。在显性模型中，它也与铂类化疗反应密切相关（调整后的OR = 1.58，95%CI = 1.05 - 2.39，p = 0.03）。此外，我们观察到CASC8 rs10505477多态性在显性模型（调整后的OR = 0.59，95%CI = 0.35 - 0.98，p = 0.04）和加性模型（调整后的OR = 0.62，95%CI = 0.43 - 0.90，p = 0.01）中与非小细胞肺癌（NSCLC）亚组的严重血液学毒性显著相关。此外，发现在显性模型中，rs10505477多态性与小细胞肺癌（SCLC）和顺铂亚组的胃肠道毒性密切相关（调整后的OR = 7.82，95%CI = 1.36 - 45.07，p = 0.02；调整后的OR = 1.94，95%CI = 1.07 - 3.53，p = 0.03）。因此，lncRNA CASC8 rs10505477可作为诊断肺癌的一种可能的风险标志物，并可用于预测肺癌患者铂类治疗的反应和毒性。
