Link between colorectal cancer and polymorphisms in the uridine-diphosphoglucuronosyltransferase 1A7and 1A1 genes

摘要

AIM: To investigate the relationship between single nucleotide polymorphisms in the uridine-diphosphoglucurono-syltransferase (UGT) UGT1A7 and UGT1A1 genes and patients suffering from colorectal cancer (CRC). METHODS: A case-control study was designed in order to investigate the genotypes of the UGT1A7 and UGT1A1 genes, which were identified by the polymerase chain reaction-restriction fragment length polymorphism (RFLP) method, for 268 CRC patients and 441 healthy controls. RESULTS: The results of simple logistical regressions revealed odds ratios (ORs) of 1.97 (P < 0.001), 1.91 (P < 0.001), and 2.03 (P < 0.001) for patients who carried the UGTlA7~*1/~*3 genotype, UGT1A7~*3 allele, and variant-211 UGT1A1 allele. The interaction of UGT1A7~*3 allele and variant-211 UGT1A1 allele produced an additive effect on the risk for the development of CRC [observed OR (2.34) greater than expected OR (1.59)]. For the 268 patients, the results of simple logistical regressions indicated that the OR of developing metastases was 4.90 (P < 0.001) and 4.89 (P < 0.001) for the individuals possessing UGT1A7~*3 allele and variant-211 UGT1A1 allele, respectively. The results of multivariate logistical regressions confirmed these findings (OR = 2.51, P= 0.01; and OR = 2.71, P= 0.01, respectively). The interaction of these two variants resulted in an additive effect on the risk for metastases amongst patients [observed OR (6.83) greater than expected OR (4.56)]. CONCLUSION: In conclusion, carriage of the UGT1A7~*3 allele, as well as variant-211 UGT1A1 allele represents a risk factor for the development of, and a determinant for, metastases associated with CRC patients.