UGT1A6 polymorphisms modulated lung cancer risk in a Chinese population.
Uridine diphosphoglucuronosyltransferases (UGTs) 1A6 is the only UGT1A isoform expressed in lung tissue. It is responsible for the detoxification of carcinogens such as benezo[a]pyrene from cigarette smoke. The purpose of this study was to evaluate the association of UGT1A6 polymorphisms and haplotypes with lung cancer risk and to evaluate the functional significance of UGT1A6 polymorphisms. Genomic DNA was isolated from leukocytes. Eight UGT1A6 polymorphisms were sequenced in a test set of 72 Chinese lung cancer patients and 62 healthy controls. Potential risk modifying alleles were validated in a separate set of 95 Chinese lung cancer patients and 100 healthy controls. UGT1A6 19T>G, 541A>G and 552A>C showed significant association with increased lung cancer risk, while UGT1A6 105C>T and IVS1+130G>T were significantly associated with reduced lung cancer risk. Multivariate logistic regression analysis demonstrated a significant association of lung cancer with UGT1A6 541A>G (OR: 3.582, 95% CI: 1.27-10.04, p = 0.015), 552A>C (OR: 5.364, 95% CI: 1.92-14.96, p = 0.001) and IVS1+130G>T (OR: 0.191, 95% CI: 0.09-0.36, p<0.001). Functional test demonstrated that UGT1A6 105C>T increased mRNA stability, providing a plausible explanation of its association with reduced lung cancer risk. Thus UGT1A6 polymorphisms may be used to identify people with increased risk of developing lung cancer.
Department of Haematology-Oncology, National University Cancer Institute of Singapore, Singapore, Singapore.
Ley-Fang
LF
Kua
Soo
S
Ross
Soo-Chin
SC
Lee
Kousaku
K
Mimura
Koji
K
Kono
Boon-Cher
BC
Goh
Wei-Peng
WP
Yong
D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014453:Glucuronosyltransferase / Q000235:genetics*; D057809:HEK293 Cells; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
C110655:UDP-glucuronosyltransferase, UGT1A6; D014453:Glucuronosyltransferase