Interaction between cytochrome P450 1A2 genetic polymorphism and cigarette smoking on the risk of hepatocellular carcinoma in a Japanese population.
Limited epidemiological evidence suggests that genetic polymorphisms of drug-metabolizing enzymes such as cytochrome P450 (CYP), glutathione S-transferase (GST) and N-acetyltransferase (NAT) may be involved in tobacco-related hepatocarcinogenesis. We conducted a case-control study, including 209 incident cases with hepatocellular carcinoma (HCC) and two different control groups [275 hospital controls and 381 patients with chronic liver disease (CLD) without HCC], to investigate whether CYP1A1, CYP1A2, CYP2A6, CYP2E1, GSTM1 and NAT2 polymorphisms are related to the risk of HCC with any interaction with cigarette smoking. Overall, no significant associations with HCC were observed for any genotypes against either control group. However, we found a significant interaction (P = 0.0045) between CYP1A2 -3860G>A polymorphism and current smoking on HCC risk when we compared HCC cases with CLD patients; adjusted odds ratios [ORs; and 95% confidence intervals (CIs)] for G/A and A/A genotypes relative to G/G genotype were 0.28 (0.12-0.66) and 0.18 (0.04-0.94), respectively, among current smokers (P trend = 0.002), as compared with 1.28 (0.80-2.06) and 0.76 (0.34-1.71), respectively, among never/former smokers (P trend = 0.96). Similarly, in CYP1A2 G/G genotype, significant risk increase was observed for current smoking (OR = 4.08, 95% CI = 2.02-8.25) or more recent cigarette use (e.g. pack-years during last 5 years, P trend = 0.0003) but not in G/A and A/A genotypes combined (OR for current smoking = 1.39, 95% CI = 0.63-3.03; P trend for pack-years during last 5 years = 0.40). These results suggest that the CYP1A2 -3860G>A polymorphism modifies the smoking-related HCC risk among CLD patients.
Imaizumi
Takeshi
T
Department of Preventive Medicine, Faculty of Medicine, Saga University, Nabeshima, Saga, Japan.
Higaki
Yasuki
Y
Hara
Megumi
M
Sakamoto
Tatsuhiko
T
Horita
Mikako
M
Mizuta
Toshihiko
T
Eguchi
Yuichiro
Y
Yasutake
Tsutomu
T
Ozaki
Iwata
I
Yamamoto
Kyosuke
K
Onohara
Shingo
S
Kawazoe
Seiji
S
Shigematsu
Hirohisa
H
Koizumi
Shunzo
S
Kudo
Sho
S
Tanaka
Keitaro
K
D000225:Adenine; D000328:Adult; D017677:Age Distribution; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005260:Female; D006147:Guanine; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008107:Liver Diseases / Q000453:epidemiology / Q000235:genetics*; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010045:Outpatients / Q000706:statistics & numerical data; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*
C402671:cytochrome P-450 CYP1A6 (fish); D006147:Guanine; D003577:Cytochrome P-450 Enzyme System; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D000225:Adenine