Journal article
The Effect of UGT1A and UGT2B Polymorphisms on Colorectal Cancer Risk: Haplotype Associations and Gene-Environment Interactions
Genes chromosomes & cancer, Vol.53(6), pp.454-466
06/2014
Handle:
https://hdl.handle.net/2376/118187
PMCID: PMC4048880
PMID: 24822274
Abstract
UDP-glucuronosyltransferases (UGTs) play an important role in the phase II metabolism of exogenous and endogenous compounds. As colorectal cancer (CRC) etiology is thought to involve the biotransformation of dietary factors, UGT polymorphisms may affect CRC risk by altering levels of exposure. Genotyping of over 1800 Caucasian subjects was completed to identify the role of genetic variation in nine
UGT1A
and five
UGT2B
genes on CRC risk. Unconditional logistic regression and haplotype analyses were conducted to identify associations with CRC risk and potential gene-environment interactions.
UGT1A
haplotype analysis found that the T-G haplotype in
UGT1A10
exon 1 (block 2: rs17864678, rs10929251) decreased colon cancer risk [proximal (OR = 0.28, 95% CI=0.11–0.69), distal (OR = 0.32, 95% CI=0.12–0.91)] and that the C-T-G haplotype in the 3′ region flanking the
UGT1A
shared exons (block 11: rs7578153, rs10203853, rs6728940) increased CRC risk in males (OR = 2.56, 95% CI=1.10–5.95). A haplotype in
UGT2B15
containing a functional variant (rs4148269, K523T) and an intronic SNP (rs6837575) was found to affect rectal cancer risk overall (OR = 2.57, 95% CI=1.21–5.04) and in females (OR = 3.08, 95% CI=1.08–8.74). An interaction was found between high NSAID use and the A-G-T haplotype (block 10: rs6717546, rs1500482, rs7586006) in the
UGT1A
shared exons that decreased CRC risk. This suggests that UGT genetic variation alters CRC risk differently by anatomical sub-site and gender and that polymorphisms in the
UGT1A
shared exons may have a regulatory effect on gene expression that allows for the protective effect of NSAIDs on CRC risk.
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Details
- Title
- The Effect of UGT1A and UGT2B Polymorphisms on Colorectal Cancer Risk: Haplotype Associations and Gene-Environment Interactions
- Creators
- Andrea Y Angstadt - Department of Public Health Sciences, Penn State College of Medicine, Hershey, PATerryl J Hartman - Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GASamuel M Lesko - Northeast Regional Cancer Institute, Scranton, PAJoshua E Muscat - Department of Pharmacology, Penn State College of Medicine, Hershey, PAJunjia Zhu - Department of Public Health Sciences, Penn State College of Medicine, Hershey, PACarla J Gallagher - Department of Public Health Sciences, Penn State College of Medicine, Hershey, PAPhilip Lazarus - Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA
- Publication Details
- Genes chromosomes & cancer, Vol.53(6), pp.454-466
- Academic Unit
- Pharmaceutical Sciences, Department of
- Identifiers
- 99900547924401842
- Language
- English
- Resource Type
- Journal article