Five functional polymorphisms of B7/CD28 co-signaling molecules alter susceptibility to colorectal cancer

• CD80 polymorphism contributes to lymph metastasis and progress of colorectal cancer.
• B7-H4 and ICOS polymorphisms alter individual susceptibility to colorectal cancer.
• miR-21-3p and miR-1207-5p inhibit CD80 and B7-H4 expression, respectively.
• miR-186-5p, miR-323b-5p, miR-1279, miR-2117 and miR-3692-3p repress ICOS expression.
• CD80, B7-H4 and ICOS polymorphisms disrupt protein expression mediated by miRNAs.

Polymorphisms within the 3′-untranslated region (3′-UTR) of genes have been proved to contribute to the risk of cancers. Here, we determined 16 putatively functional polymorphisms in the 3′-UTR of 11 B7/CD28 genes in 382 colorectal cancer patients and 714 healthy controls. Statistical analysis revealed that ICOS rs4404254-C-allele carriers (p = 0.0014), rs1559931-A-allele carriers (p = 0.0027), and rs4675379-C-allele carriers (p = 0.026) were significantly fewer in patients than those in controls. B7-H4-rs13505-GG homozygotes were more prevalent in patients (p = 0.03). CD80-rs7628626-GT was apparently less in the patients with lymph node metastasis (p = 0.004) or in advanced stage (p = 0.037). Furthermore, we found that these polymorphisms impacted the regulatory role of miR-21-3p, miR-186-5p, miR-323b-5p, miR-1207-5p, miR-1279, miR-2117, and miR-3692-3p in the expression of the B7/CD28 molecules. Our findings suggest that rs7628626, rs13505, rs4404254, rs1559931, and rs4675379, through disrupting the regulatory role of miRNAs in the expression of B7/CD28 molecules, contribute to the occurrence and progress of colorectal cancer.