Wu Meng-Feng, Wang Yun-Chi, Li Hsin-Ting, Chen Wei-Chun, Liao Cheng-Hsi, Shih Tzu-Ching, Chang Wen-Shin, Tsai Chia-Wen, Hsia Te-Chun, Bau DA-Tian
Terry Fox Cancer Research Laboratory, Translational Medicine Research Center, China Medical University Hospital, Taichung, Taiwan, R.O.C.
Division of Chest Surgery, Department of Surgery, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan, R.O.C.
Anticancer Res. 2018 Nov;38(11):6321-6327. doi: 10.21873/anticanres.12989.
BACKGROUND/AIM: Lung cancer is the leading cause of cancer-related death and a better marker for advanced personalized therapeutic approaches, such as immunotherapies, is in urgent need. Interleukin-12 (IL-12) is a cytokine that has been reported to exhibit potent tumoricidal effects, however, the contribution of IL-12 genotypes to lung cancer is still largely unrevealed. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) in IL-12A and IL-12B are associated with lung cancer in a Taiwanese population.
Genotypes of 358 lung cancer patients and 716 controls were determined by the polymerase chain reaction-restriction fragment length polymorphism method.
The distributions of genotypic (p=0.0036) and allelic (p=0.0005) frequencies of IL-12A rs568408 demonstrated significant differences between cases and controls. In detail, the AA genotype of IL-12A rs568408 was associated with a significantly elevated risk of lung cancer compared with the GG genotype (odds ratio(OR)=2.41, 95% confidence interval(CI)=1.36-4.29, p=0.0021). No difference was observed regarding IL-12A rs2243115 and IL-12B rs3212227 genotypes between the case and control groups. In addition, the results of interaction analysis showed that the AA genotype of IL-12A rs568408 was associated with elevated lung cancer risk, especially among those with smoking habits (p=0.0043).
IL-12A rs568404 AA genotype may contribute to the etiology and serve as a genomic determinant of lung cancer in Taiwanese, especially smokers.
背景/目的：肺癌是癌症相关死亡的主要原因，迫切需要一种更好的标志物用于先进的个性化治疗方法，如免疫疗法。白细胞介素-12（IL-12）是一种据报道具有强大杀肿瘤作用的细胞因子，然而，IL-12基因分型对肺癌的影响仍 largely未明。本研究的目的是调查IL-12A和IL-12B中的单核苷酸多态性（SNP）是否与台湾人群的肺癌相关。
采用聚合酶链反应-限制性片段长度多态性方法测定358例肺癌患者和716例对照的基因型。
IL-12A rs568408的基因型（p=0.0036）和等位基因（p=0.0005）频率分布在病例组和对照组之间存在显著差异。具体而言，与GG基因型相比，IL-12A rs568408的AA基因型与肺癌风险显著升高相关（优势比（OR）=2.41，95%置信区间（CI）=1.36-4.29，p=0.0021）。病例组和对照组在IL-12A rs2243115和IL-12B rs3212227基因型方面未观察到差异。此外，相互作用分析结果显示，IL-12A rs568408的AA基因型与肺癌风险升高相关，尤其是在有吸烟习惯的人群中（p=0.0043）。
IL-12A rs568404 AA基因型可能在台湾人群，尤其是吸烟者的肺癌病因中起作用，并可作为肺癌的基因组决定因素。
