Polymorphisms in UGT2B4 and susceptibility to pancreatic cancer

Abstract

As an important enzyme in the conjugation phase of drug clearance, UGT2B4 helps metabolize various endogenous and exogenous substances, and polymorphisms in the corresponding gene can influence enzyme activity. This study investigated the association between polymorphisms in UGT2B4 and the risk of developing pancreatic cancer in Han Chinese individuals. A hospital-based case-control study was conducted with 1579 healthy controls and 406 pancreatic cancer patients from China. Genomic DNA was obtained from peripheral blood lymphocytes. Time-of-flight mass spectrometry was used to genotype polymorphic loci in UGT2B4, and the association between these polymorphisms and susceptibility to pancreatic cancer was expressed as odds ratios (ORs) with 95% confidence intervals (CIs), as calculated using multivariable logistic regression analysis. The rs1131878C > T polymorphism (NT_016354.20: g.10558805C > T) in UGT2B4 was associated with an increased pancreatic cancer risk. Compared to the C/C genotype, the C/T genotype conferred 1.39 times higher the pancreatic cancer risk (95% CI = 1.09-1.77; P = 0.007), and the T/T genotype conferred 2.97 times higher the pancreatic cancer risk (95% CI = 1.24-7.08; P = 0.014). In contrast, compared with the A/A genotype, the A/C genotype at the rs3822179 locus in UGT2B4 (NT_016354.20: g.10569096C > A) bestowed a 20% risk reduction (OR = 0.80, 95% CI = 0.67-0.95; P = 0.011). However, the risk was not significantly reduced with the C/C genotype (OR = 0.77, 95% CI = 0.52-1.14, P = 0.191). Polymorphisms in UGT2B4 affect the risk of pancreatic cancer occurrence in Han Chinese individuals.

Keywords: UGT2B4; hereditary susceptibility; pancreatic cancer; polymorphism.

Figure 1

UGT2B4 haplotype domain mapping using genotype frequencies of polymorphic loci. A haplotype domain map was constructed using single nucleotide polymorphisms (SNPs) within UGT2B4, based on SNP frequency data for Han Chinese individuals residing in Beijing, available from the International Hap Map Project [11]. Red arrows point to rs11249442, rs1826690, and rs3822179, located in the promoter region, and to rs1131878, located in the 3’ untranslated region.