Interaction between cytochrome P450 1A2 genetic polymorphism and cigarette smoking on the risk of hepatocellular carcinoma in a Japanese population
Interaction between cytochrome P450 1A2 genetic polymorphism and cigarette smoking on the risk of hepatocellular carcinoma in a Japanese population
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DOI：
10.1093/carcin/bgp191
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发表时间：
2009-10-01
期刊：
影响因子：
4.7
通讯作者：
Tanaka, Keitaro
中科院分区：
文献类型：
--
作者：
Imaizumi, Takeshi;Higaki, Yasuki;Tanaka, Keitaro
有限的流行病学证据表明，细胞色素P450、谷胱甘肽S转移酶和N-乙酰转移酶等药物代谢酶基因多态性可能与烟草相关肝癌的发生有关。我们进行了一项病例对照研究，包括209例肝细胞癌(HCC)病例和两个不同的对照组[275名医院对照和381名慢性肝病(CLD)非肝癌患者]，以探讨CYP1A1、CYP1A2、CYP2A6、CYP2E1、GSTM1和Nat2基因多态性是否与吸烟有任何交互作用与肝癌的风险相关。总体而言，与对照组相比，没有观察到任何基因类型与肝细胞癌的显著关联。然而，当我们比较肝细胞癌患者和慢性阻塞性肺疾病患者时，我们发现细胞色素P1A2-3860G&A基因多态性和当前吸烟对肝癌风险有显著的交互作用(P=0.0045)；调整后的优势比[ORs；在吸烟者中，G/A和A/A基因型相对于G/G基因型的95%可信区间分别为0.28(0.12~0.66)和0.18(0.04~0.94)(P趋势=0.002)，而从未吸烟者和曾经吸烟者分别为1.28(0.80~2.06)和0.76(0.34~1.71)(P趋势=0.96)。与之相似的是，在G/A和A/A两种基因型的联合作用下，当前吸烟(OR=4.0 8，95%CI=2.0 2~8.2 5)或最近吸烟(如近5年吸烟，P趋势=0.0003)的危险性显著增加(OR=1.3 9，95%CI=0.6 3~3.0 3；最近5年吸烟的P趋势=0.40)。这些结果表明，在CLD患者中，CYP1A2-3860G>；A基因多态性改变了吸烟相关的肝细胞癌风险。
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.