Han Feifei, Qian Lu, Zhang Yi, Liu Ping, Li Rui, Chen Mingwei
Department of Respiratory Medicine, The First Afliated Hospital of School of Medicine of Xi'an Jiaotong University, #277 Yanta West Road, Xi'an, Shaanxi, 710061, China.
Department of Endocrinology, Xi'an No.3 Hospital, the Affiliated Hospital of Northwest University, Xi'an, 710018, Shaanxi, China.
Funct Integr Genomics. 2022 Jun;22(3):331-340. doi: 10.1007/s10142-022-00827-x. Epub 2022 Feb 25.
The mRNA levels of C2CD4A and C2CD4B were dysregulation in lung cancer (LC). We aimed to evaluate the role of C2CD4A/B variants in LC susceptibility.
There were 710 cases with LC and 710 healthy controls enrolled in the study. The genotyping of twelve variants in C2CD4A/B was carried out by Agena MassARRAY system. Odds ratios (ORs) were calculated by logistic regression analysis to assess the relationship between these variants and LC predisposition.
Rs8037894 (OR = 0.81, p = 0.005), rs7172432 (OR = 0.83, p = 0.013), rs11856307 (OR = 0.86, p = 0.043), and rs1436953 (OR = 0.79, p = 0.002) were related to the reduced risk of LC. Besides, the relation of rs7172432 with LC risk in subjects aged > 60 years was observed. Rs4502156 conferred to the increased LC risk, while rs1436953 was associated with the lower susceptibility to LC among males. Rs731820, rs4502156, rs11071657, rs7172432, and rs11856307 contributed to the predisposition of LC among subjects with BMI > 24 kg/m, while rs7495253 was associated with an increased risk of LC in subjects with BMI ≤ 24 kg/m. The increased LC risk was found in rs4502156, while the protective risk effect of rs8037894, rs7172432, rs11856307, and rs1436953 on the occurrence of LC was observed in smokers and non-drinkers. Moreover, rs7495253 and rs7495931 had a higher risk of lymphatic metastasis. Rs1436953 was related to the reduced risk of lung adenocarcinoma, while rs4502156, rs8037894, rs7172432, rs11856307, and rs1436953 were related to the risk of small cell carcinoma.
Our results first display that C2CD4A/B polymorphisms served as protective factors for LC predisposition in a Chinese Han population. These findings could provide new biological insight into the understanding of C2CD4A/B genes on LC pathogenesis.
肺癌（LC）中C2CD4A和C2CD4B的mRNA水平存在失调。我们旨在评估C2CD4A/B变异体在肺癌易感性中的作用。
本研究纳入了710例肺癌患者和710名健康对照。采用Agena MassARRAY系统对C2CD4A/B中的12个变异体进行基因分型。通过逻辑回归分析计算比值比（OR），以评估这些变异体与肺癌易感性之间的关系。
Rs8037894（OR = 0.81，p = 0.005）、rs7172432（OR = 0.83，p = 0.013）、rs11856307（OR = 0.86，p = 0.043）和rs1436953（OR = 0.79，p = 0.002）与肺癌风险降低相关。此外，观察到rs7172432与年龄>60岁的受试者的肺癌风险有关。Rs4502156增加了肺癌风险，而rs1436953与男性对肺癌的易感性较低有关。Rs731820、rs4502156、rs11071657、rs7172432和rs11856307导致体重指数（BMI）>24 kg/m²的受试者易患肺癌，而rs7495253与BMI≤24 kg/m²的受试者患肺癌的风险增加有关。Rs4502156增加了肺癌风险，而在吸烟者和不饮酒者中观察到rs8037894、rs7172432、rs11856307和rs1436953对肺癌发生的保护作用。此外，rs7495253和rs7495931发生淋巴转移的风险较高。Rs1436953与肺腺癌风险降低有关，而rs4502156、rs8037894、rs7172432、rs11856307和rs1436953与小细胞癌风险有关。
我们的结果首次表明，C2CD4A/B多态性是中国汉族人群肺癌易感性的保护因素。这些发现可为理解C2CD4A/B基因在肺癌发病机制中的作用提供新的生物学见解。
