Colorectal Cancer
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2005; 11(21): 3250-3254
Published online Jun 7, 2005. doi: 10.3748/wjg.v11.i21.3250
Link between colorectal cancer and polymorphisms in the uridine-diphosphoglucuronosyltransferase 1A7 and 1A1 genes
Kung-Sheng Tang, Hui-Fen Chiu, Hong-Hwa Chen, Hock-Liew Eng, Chia-Jung Tsai, Hsiu-Chen Teng, Ching-Shan Huang
Kung-Sheng Tang, Department of Medical Technology, Fooyin University, Kaohsiung, Taiwan; Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, China
Hui-Fen Chiu, Graduate Institute of Medicine and Department of Pharmacology, Kaohsiung Medical University, Kaohsiung, Taiwan, China
Hong-Hwa Chen, Department of Colorectal Surgery, Chang Gung Memorial Hospital, Kaohsiung, Taiwan, China
Hock-Liew Eng, Chia-Jung Tsai, Department of Pathology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan, China
Hsiu-Chen Teng, Department of Medical Management, Fooyin University, Kaohsiung, Taiwan, China
Ching-Shan Huang, Department of Medical Technology, Fooyin University, Kaohsiung, Taiwan; Department of Laboratory Medicine, Cathay General Hospital, Taipei, Taiwan, China
Author contributions: All authors contributed equally to the work.
Supported by a Grant From the National Science Council (NSC 93-3112-B-242-001), Taipei, Taiwan, China
Correspondence to: Professor Ching-Shan Huang, Department of Medical Technology, Fooyin University, 151 Chin-Hsueh Road, Ta-Liao Hsiang, Kaohsiung Hsien 831, Taiwan; Department of Laboratory Medicine, Cathay General Hospital, 280, Jen Ai-Road, Section 4, Taipei 106, Taiwan, China. chsh.huang@msa.hinet.net
Telephone: +886-22-6360450 Fax: +886-28-7725983
Received: October 29, 2004
Revised: October 30, 2004
Accepted: December 1, 2004
Published online: June 7, 2005
Abstract

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 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)].

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.

Keywords: Colorectal cancer; UGT1A7*3 allele; Variant-211 UGT1A1 allele; Metastases