Genetic polymorphisms of the uridine diphosphate glucuronosyltransferase 1A7 and colorectal cancer risk in relation to cigarette smoking and alcohol drinking in a Chinese population.
BACKGROUND
The impact of uridine diphosphate glucuronosyltransferase 1A7 (UGT1A7) polymorphisms on genetic susceptibility to digestive system cancer has received close attention since the discovery by Guillemette, the polymorphisms of which may alter enzyme activity. To clarify the allele frequency distribution and its association with risk of colorectal cancer, a population-based case-control study was carried out in Chinese population.


METHODS
A total of 140 patients with colorectal cancer and 280 cancer-free frequency-matched controls from a follow-up cohort population established in 1989, were enrolled. For the UGT1A7 polymorphisms analysis, polymerase chain reaction (PCR)-based genotyping techniques including semi-nested PCR, allele-specific PCR and PCR-restriction fragment length polymorphism (RFLP) were developed.


RESULTS
The variant allele frequencies in patients and controls were 50.0% and 38.6%, respectively, which were significantly associated with risk of colorectal cancer (odds ratio [OR]: 1.59; 95% confidence interval [CI]: 1.19-2.13). For the variant genotypes analysis, *2/*2 and *3/*3 exhibited a significant association with risk of colorectal cancer (OR: 7.80, 95%CI: 2.66-22.87; OR: 3.47, 95%CI: 1.51-7.97, respectively). Stratification analysis indicated that in previous-current cigarette smoking (cigarette smoking history), current cigarette smoking (current cigarette smoking status), previous-current alcohol drinking (alcohol drinking history) or current alcohol drinking individuals (current alcohol drinking status), the risk developing colorectal cancer increased: OR (95%CI), 2.81 (0.97-8.11), 3.39 (1.19-9.67), 2.89 (0.99-8.46) and 3.14 (1.09-9.09), respectively.


CONCLUSIONS
UGT1A7 polymorphisms may have a significant modifying effect on colorectal cancer risk, which may interact with environmental factors, cigarette smoking and alcohol drinking in colorectal carcinogenesis.
Chen
Kun
K
Department of Epidemiology and Health Statistics, Zhejiang University, School of Public Health, 353 Yan-an Road, Hangzhou, Zhejiang 310031, China. ck@zju.edu.cn
Jin
Mingjuan
M
Zhu
Yimin
Y
Jiang
Qinting
Q
Yu
Weiping
W
Ma
Xinyuan
X
Yao
Kaiyan
K
D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking; D044466:Asian People / Q000235:genetics; D002681:China / Q000453:epidemiology; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking
D014453:Glucuronosyltransferase; C107611:UDP-glucuronosyltransferase, UGT1A7