The diplotype of UGT1A1 and UGT1A9 genes may predict an increased risk for lung cancer
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Uridine diphosphoglucuronosyltransferases (UGTs) are a superfamily of enzymes that catalyze the glucuronidation of xenobiotics and endobiotics. To reveal occurrence of UGT1A polymorphisms, we retrospectively aimed to characterize UGT1A1-UGT1A9 haplotype structures in Koreans and gain insight on their association with increased cancer incidence. We genotyped UGT1A1 (-3279T>G, -3156G>A, -53(TA)6>7, 211G>A and 686C>A), and UGT1A9 (-2152C>T, -275T>A and -118T9>10) variants by direct sequencing in 98 lung cancer patients and 154 healthy subjects. The haplotype structure across the UGT1A locus was constituted using 4 haplotype-tagging SNPs (htSNPs). For polymorphisms in UGT1A1 and UGT1A9, no significant differences in allele frequency were found between the two groups. The strongest linkage disequilibrium (LD) was discovered between UGT1A1 -53(TA)6>7 and 211G>A, and lowest LD was observed between the UGT1A1 -53(TA)6>7 and UGT1A9 -118T9>10 variant. Eight UGT1A1-UGT1A9 haplotypes were provided and the three most common haplotypes were D-T-6-G, N-T-6-A, and N-G-6-G (73% of all haplotypes) in two groups. Ultimately, no significant differences exist in haplotype frequency between cases and controls (likelihood ratio statistic 20.06, df = 15, p = 0.08). Logistic regression analysis presented a statistically significant association between UGT1A1-UGT1A9 diplotypes including 4 minor alleles and increased lung cancer incidence (OR 31.32, 95% CI 4.34-226.23). There was statistically significant difference in the distribution of the UGT1A1 and UGT1A9 diplotype frequency between cases and controls. These results suggest that the diplotype in the UGT1A1 and UGT1A9 gene might be associated with an increased risk for lung cancer among Korean.
Abstract
Uridine diphosphoglucuronosyltransferases (UGTs) are a superfamily of enzymes that catalyze the glucuronidation of xenobiotics and endobiotics. To reveal occurrence of UGT1A polymorphisms, we retrospectively aimed to characterize UGT1A1-UGT1A9 haplotype structures in Koreans and gain insight on their association with increased cancer incidence. We genotyped UGT1A1 (-3279T>G, -3156G>A, -53(TA)6>7, 211G>A and 686C>A), and UGT1A9 (-2152C>T, -275T>A and -118T9>10) variants by direct sequencing in 98 lung cancer patients and 154 healthy subjects. The haplotype structure across the UGT1A locus was constituted using 4 haplotype-tagging SNPs (htSNPs). For polymorphisms in UGT1A1 and UGT1A9, no significant differences in allele frequency were found between the two groups. The strongest linkage disequilibrium (LD) was discovered between UGT1A1 -53(TA)6>7 and 211G>A, and lowest LD was observed between the UGT1A1 -53(TA)6>7 and UGT1A9 -118T9>10 variant. Eight UGT1A1-UGT1A9 haplotypes were provided and the three most common haplotypes were D-T-6-G, N-T-6-A, and N-G-6-G (73% of all haplotypes) in two groups. Ultimately, no significant differences exist in haplotype frequency between cases and controls (likelihood ratio statistic 20.06, df = 15, p = 0.08). Logistic regression analysis presented a statistically significant association between UGT1A1-UGT1A9 diplotypes including 4 minor alleles and increased lung cancer incidence (OR 31.32, 95% CI 4.34-226.23). There was statistically significant difference in the distribution of the UGT1A1 and UGT1A9 diplotype frequency between cases and controls. These results suggest that the diplotype in the UGT1A1 and UGT1A9 gene might be associated with an increased risk for lung cancer among Korean.
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