Association between polymorphisms in UDP-glucuronosyltransferase 1A6 and 1A7 and colorectal cancer risk.
Genetic polymorphisms of uridine diphosphate-glucuronosyltransferases 1A6 (UGT1A6) and 1A7 (UGT1A7) may lead to genetic instability and colorectal cancer carcinogenesis. Our objective was to measure the interaction between polymorphisms of these repair genes and tobacco smoking in colorectal cancer (CRC). A total of 68 individuals with CRC and 112 non-cancer controls were divided into non-smoker and smoker groups according to pack-years of smoking. Genetic polymorphisms of UGT1A6 and UGT1A7 were examined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). We found a weak association of UGT1A6 polymorphisms with CRC risk (crude odds ratio [OR], 1.65; 95% confidence interval [95%CI], 0.9-3.1, P=0.107; adjusted OR 1.95, 95%CI 1.0-3.8, P=0.051). The ORs for the UGT1A7 polymorphisms were statistically significant (crude OR: 26.40, 95%CI: 3.5-198.4, P=0.001; adjusted OR: 21.52, 95%CI: 2.8-164.1, P=0.003). The joint effect of tobacco exposure and UGT1A6 polymorphisms was significantly associated with colorectal cancer risk in non-smokers (crude OR, 2.11; 95%CI, 0.9-5.0, P=0.092; adjusted OR 2.63, 95%CI 1.0-6.7, P=0.042). In conclusion, our findings suggest that UGT1A6 and UGT1A7 gene polymorphisms are associated with CRC risk in the Japanese population. In particular, UGT1A6 polymorphisms may strongly increase CRC risk through the formation of carcinogens not associated with smoking.
Faculty of Health Sciences, Kobe University Graduate School of Health Sciences, and Clinical Laboratory, Otemae Hospital, Osaka, Japan. osawak@kobe-u.ac.jp
Kayo
K
Osawa
Chiaki
C
Nakarai
Minami
M
Akiyama
Ryuta
R
Hashimoto
Akimitsu
A
Tsutou
Juro
J
Takahashi
Yuko
Y
Takaoka
Shiro
S
Kawamura
Etsuji
E
Shimada
Kenichi
K
Tanaka
Masaya
M
Kozuka
Masahiro
M
Yamamoto
Yoshiaki
Y
Kido
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D012007:Rectum / Q000378:metabolism; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
C110655:UDP-glucuronosyltransferase, UGT1A6; D014453:Glucuronosyltransferase; C524630:UGT1A7 protein, human