Abstract
To examine the role of IL-22 gene in colorectal cancer (CRC) susceptibility, we identified causative genetic polymorphisms in promoter region of IL-22 gene and explored the mechanism underlying their contribution to CRC development in a Chinese population of Hubei province. 13 target single nucleotide polymorphisms (SNPs) in IL-22 gene promoter were genotyped in 787 CRC patients (426 colon cancer and 361 rectal cancer) and 800 normal controls. The results demonstrated that the rs2227478 T > C polymorphism was significantly associated with the risk of colon cancer, rectal cancer and CRC, and the C allele was associated with a decreased cancer risk than the T allele. In CRC tissue samples, the subjects with CT+CC genotypes of rs2227478 had lower levels of IL-22 mRNA than the subjects with TT genotypes. Further functional analysis revealed that the transcription repressor Sp1 possessed a higher binding affinity to the C allele than the T allele. Collectively, the rs2227478 T > C is a functional genetic polymorphism that significantly reduces the CRC risk in a Han Chinese population.
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