Association of CYP1A2 genetic polymorphisms with hepatocellular carcinoma susceptibility: a case-control study in a high-risk region of China.
OBJECTIVE
Aflatoxin B1 exposure is one of the major risk factors for hepatocellular carcinoma (HCC). CYP1A2 is a cytochrome P450 isoenzyme that plays an important role in the bioactivation of AFB1 to its carcinogenic metabolite. The study was designed to assess whether genetic polymorphisms in CYP1A2 are associated with HCC susceptibility in a high-risk region.


METHODS
A case-control study of 431 HCC cases and 550 cancer-free controls recruited from an HCC endemic region in China was carried out. Three single nucleotide polymorphisms, namely -3860G > A (CYP1A2*1C), -3113G > A, and 5347T > C (CYP1A2*1B) were genotyped by polymerase chain reaction-restriction fragment length polymorphism methods.


RESULTS
Homozygous carriers of the major haplotype -3860G/-3113G/5347C were associated with increased HCC susceptibility in the overall population (odds ratio [OR] = 1.65, 95% confidence interval [CI]: 1.11-2.46, P = 0.014), in HBsAg seronegative individuals (OR = 2.69, 95% CI: 1.43-5.06, P = 0.002), and in heavy smokers (OR = 2.14, 95% CI: 1.21-3.80, P=0.009). In addition, individuals carrying at least one CYP1A2*1C allele showed significantly decreased HCC risk (OR = 0.49, 95% CI: Q0.27-0.86, P = 0.013) in the HBsAg seronegative subpopulation. Furthermore, as compared with HBsAg seropositive patients, wild-type homozygotes of the CYP1A2*1C polymorphism were significantly over-represented in HBsAg seronegative patients (P = 0.024). No significant association between CYP1A2 genetic polymorphisms and HCC risk was observed in either HBsAg seropositive individuals or non-smokers.


CONCLUSIONS
CYP1A2 genetic polymorphisms are associated with HCC susceptibility in smokers and HBsAg seronegative individuals in the Fusui endemic region.
Chen
Xiaoping
X
Department of Genomics & Proteomics, Beijing Institute of Radiation Medicine, Beijing, PR China.
Wang
Haijian
H
Xie
Weimin
W
Liang
Renxiang
R
Wei
Zhongliang
Z
Zhi
Lianteng
L
Zhang
Xiumei
X
Hao
Bingtao
B
Zhong
Shaofei
S
Zhou
Gangqiao
G
Zhang
Lingqiang
L
Gao
Xue
X
Zhu
Yunping
Y
He
Fuchu
F
D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics / Q000379:methods*; D011110:Polymorphism, Genetic; D012306:Risk; D012907:Smoking
D019388:Cytochrome P-450 CYP1A2