Carcinogenesis Advance Access originally published online on July 30, 2009
Carcinogenesis 2009 30(10):1729-1734; doi:10.1093/carcin/bgp191
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Interaction between cytochrome P450 1A2 genetic polymorphism and cigarette smoking on the risk of hepatocellular carcinoma in a Japanese population
1 Department of Preventive Medicine
2 Department of Radiology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan
3 Laboratory of Exercise Physiology, Faculty of Sports and Health Science, Fukuoka University, Fukuoka 814-0180, Japan
4 Asakura Health Welfare Environment Office, Asakura 830-0068, Japan
5 Department of Internal Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan
6 Department of Internal Medicine, Saga Prefectural Hospital Koseikan, Saga 840-8571, Japan
7 Department of General Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan
* To whom correspondence should be addressed. Tel: +81 (0) 952 34 2280; Fax: +81 (0) 952 34 2065; Email: tanakake{at}post.saga-med.ac.jp
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.
Abbreviations: CYP, cytochrome P450; GST, glutathione S-transferase; NAT, N-acetyltransferase; HCC, hepatocellular carcinoma; CLD, chronic liver disease; OR, odds ratio; CI, confidence interval; HBV, hepatitis B virus; HCV, hepatitis C virus; HBsAg, hepatitis B surface antigen; HCVAb, antibody to HCV; PCR, polymerase chain reaction
Received June 8, 2009; revised July 5, 2009; accepted July 27, 2009.