C7基因调节区遗传变异对结直肠癌易感性的影响研究

目的 探讨补体7(C7)基因遗传变异与结直肠癌易感性的关系。方法 利用GEPIA数据库分析基因C7在结直肠癌组织与正常组织中的表达差异；利用TIMER数据库分析C7表达及拷贝数变异与结直肠癌免疫细胞浸润的相关关系。采用病例对照研究分析C7遗传变异对结直肠癌发病风险的影响。使用PCR-限制性片段长度多态性分析对C7 rs1061429和rs1376178单核苷酸多态性（SNP）进行基因分型。使用非条件logistic回归计算比值比（OR）和95%置信区间（CI），分析C7rs1061429和rs1376178遗传变异与结直肠癌易感性的关系。结果 与结直肠正常组织相比，C7在结直肠癌组织中的表达显著降低（P<0.05）。C7表达及拷贝数变异可影响结直肠癌免疫细胞浸润。与C7 rs1061429 CC基因型携带者相比，CA基因型携带者可显著增加直肠癌发病风险（OR=1.42,95%CI:1.08～1.86）。与C7 rs1376178 CC基因型携带者相比，CA基因型携带者的结肠癌发病风险增加（OR=1.50,95%CI:1.06～2.10）,CA或AA基因型携带者有较高的直肠癌发病风...

Influence of genetic variation in C7 gene regulatory regions on susceptibility to colorectal cancer

  Objective   This study aimed to investigate the influence of genetic variation in complement component 7 (C7) on the susceptibility to colorectal cancer.   Methods  GEPIA database was used to analyze the differential expression of gene C7 in colorectal cancer tissues and colorectal normal tissues. The influence of C7 expression and copy number variation on immune cell infiltration in colorectal cancer were analyzed by using TIMER database. Case-control study was used to evaluate the relationship between C7 genetic variation and the risk of colorectal cancer. The single nucleotide polymorphism (SNP) of C7 rs1061429 and rs1376178 was genotyped using PCR-restriction fragment length polymorphism analysis. Unconditioned logistic regression analysis was used to calculate odd ratio (OR) and 95% confidence interval (CI) to analyze the relationship between polymorphism of C7 rs1061429 and rs1376178 and the susceptibility to colorectal cancer.   Results   C7 had significantly decreased expression in colorectal cancer tissues than in colorectal normal tissues (P＜0.05). C7 expression and copy number variation were correlated with the immune cell infiltration in colorectal cancer. Compared with C7 rs1061429 CC genotype carriers, CA genotype carriers had a significantly increased risk of rectal cancer (OR=1.42, 95%CI: 1.08–1.86). Compared with C7 rs1376178 CC genotype carriers, CA genotype carriers had increased the risk of colon cancer (OR=1.50, 95%CI: 1.06–2.10), CA or AA genotype carriers had increased the risk of rectal cancer (OR=1.46, 95%CI: 1.06–2.03; OR=1.57, 95%CI: 1.09?2.28). Stratified analysis of colon cancer susceptibility showed that compared with C7 rs1376178 CC genotype carriers, C7 rs1376178 CA genotype increased the risk of colon cancer in women (OR=2.01, 95%CI: 1.18?3.43), non-smokers (OR=1.70, 95%CI: 1.14?2.54) and non-drinkers (OR=1.57, 95%CI: 1.06–2.33). Stratified analysis on rectal cancer susceptibility showed that compared with C7 rs1061429 CC genotype carriers, C7 rs1061429 CA genotype increased the risk of rectal cancer in men (OR=1.64, 95%CI: 1.17?2.31) and younger age groups (OR=1.58, 95%CI: 1.07?2.33). Compared with C7 rs1376178 CC genotype carriers, C7 rs1376178 AA genotype increased the risk of rectal cancer in women (OR=1.93, 95%CI: 1.05?3.54), CA or AA genotype increased the risk of rectal cancer in younger age groups (OR=1.86 or OR=2.23), non-smokers (OR=1.55 or OR=1.80), non-drinkers (OR=1.51 or OR=1.62) (P＜0.05).   Conclusion  C7 plays an important role in the development of colorectal cancer. C7 rs1061429 and rs1376178 polymorphism might interact with environmental factors to influence the susceptibility of colorectal cancer.