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      Link between colorectal cancer and polymorphisms in the uridine-diphosphoglucuronosyltransferase 1A7 and 1A1 genes.

      World journal of gastroenterology : WJG
      Adult, Aged, Aged, 80 and over, Colorectal Neoplasms, epidemiology, genetics, Female, Genetic Linkage, Glucuronosyltransferase, Humans, Male, Middle Aged, Polymorphism, Genetic, Risk Factors

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          Abstract

          To investigate the relationship between single nucleotide polymorphisms in the uridine-diphosphoglucuronosyltransferase (UGT) UGT1A7 and UGT1A1 genes and patients suffering from colorectal cancer (CRC). 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. 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 UGT1A7*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)). 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.

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