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.