MICA-129 Met/Met contributes to the susceptibility of colorectal cancer

The highly polymorphic human major histocompatibility complex class I chain-related gene A (MICA) regulates immune surveillance and destroys tumor cells by activating its receptor, the natural killer group 2D. This study aimed to examine a single nucleotide polymorphism of this gene at codon 129 (MICA-129) in association with colorectal cancer (CRC). Using PCR sequencing, the MICA-129 polymorphism was examined in 104 patients with CRC and 536 healthy controls. Specific MICA-129 single nucleotide polymorphism was analyzed for its association with CRC susceptibility, clinical phenotypes, and selected CRC-associated microsatellite instability, driver gene mutation, immune checkpoint programmed death ligand 1, and diagnostic biomarkers carbohydrate antigen 19-9 and carcinoembryonic antigen. The MICA-129 heterozygous A/G (Met/Val) genotype was associated with less aggressive clinical characteristics, such as a reduced prevalence of the ulcerated subtype (P = .0489, OR = 0.59) and lymph node involvement (P = .0217, OR = 0.46). Conversely, the MICA-129 homozygous allele A/A (Met/Met) variant was related to more advanced clinical characteristics, such as increased tumor invasion depth (T3/4; P = .0261, OR = 2.10), driver gene mutation (P = .0363, OR = 2.65), and KRAS mutation (P = .0392, OR = 2.23). Additionally, patients with carbohydrate antigen 19-9-positive CRC had a lower MICA-129 Met/Val variation, whereas those with carcinoembryonic antigen-positive CRC had a higher MICA-129 Met/Met variant (P = .0330/OR = 0.22 and P = .0034/OR = 2.99, respectively).