Evaluation of CYP2A6 genetic polymorphisms as determinants of smoking behavior and tobacco-related lung cancer risk in male Japanese smokers
Evaluation of CYP2A6 genetic polymorphisms as determinants of smoking behavior and tobacco-related lung cancer risk in male Japanese smokers
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DOI：
10.1093/carcin/bgh258
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发表时间：
2004-12-01
期刊：
影响因子：
4.7
通讯作者：
Kamataki, T
中科院分区：
文献类型：
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作者：
Fujieda, M;Yamazaki, H;Kamataki, T
我们以前报道过，细胞色素P450 2A6(*)4纯合子患肺癌的风险较低。这项研究的目的是阐明最近发现的具有新的CYP2A6变异的受试者是否会发现吸烟行为的改变和患肺癌的风险。对1094例日本男性吸烟者和611例对照进行了流行病学研究。研究发现，携带(*)4/(*)7、(*)4/(*)10、(*)7/(*)7、(*)7/(*)9和(*)4/(*)4基因携带者的每日吸烟量显著低于携带(*)1/(*)1基因携带者(P<0.01)。即使在根据香烟消费量进行调整后，携带CYP2A6(*)1/(*)4、(*)1/(*)7、(*)1/(*)9、(*)1/(*)10、(*)4/(*)4、(*)4/(*)7、(*)4/(*)9、(*)4/(*)9、(*)7/(*)7和(*)7/(*)9等位基因携带者与(*)1/(*)1等位基因携带者比较，差异有统计学意义(P<；0.05)。将受试者分为4组，第1组((*)1/(*)1)，第2组((*)1和变异等位基因杂合子)，第3组(除(*)4/(*)4外的变异等位基因杂合子和纯合子)和第4组((*)4/(*)4)，发现携带CYP2A6等位基因变异的人群患肺癌的风险较低{第2组，OR为0.59[95%可信区间(CI)，0.44~0.79]；第3组，OR为0.52(95%CI，0.37~0.72)；第4组，OR为0.30(95%CI，0.16~0.57)}。与不吸烟的人相比，重度吸烟者患肺癌的风险降低更明显。进一步的分层分析显示，在第4组中，鳞癌和小细胞癌的OR值分别为0.07和0.10，低于腺癌的OR值(0.39)。这些结果表明，CYP2A6不仅是影响吸烟行为的主要决定因素之一，而且是影响吸烟相关肺癌易感性的主要因素之一。
We reported previously that subjects homozygous for the cytochrome P450 2A6 (CYP2A6) (*)4 have a lower risk of lung cancer. The purpose of this study was to clarify whether or not the alterations of smoking behavior and risk for lung cancer could be found in subjects possessing novel CYP2A6 variants discovered recently. An epidemiological study was performed with 1094 cases and 611 controls in male Japanese smokers. It was found that the amounts of daily cigarette consumption in subjects who harbored CYP2A6(*)4/(*)7, (*)4/(*)10, (*)7/(*)7, (*)7/(*)9 and (*)4/(*)4 genotypes were significantly less than those in subjects carrying the (*)1/(*)1 genotype (P < 0.01). Even after adjustment with cigarette consumption, the adjusted odds ratios (ORs) for lung cancer were significantly lower in subjects who harbored CYP2A6(*)1/(*)4, (*)1/(*)7, (*)1/(*)9, (*)1/(*)10, (*)4/(*)4, (*)4/(*)7, (*)4/(*)9, (*)7/(*)7 and (*)7/(*)9 genotypes than those who possessed the (*)1/(*)1 genotype (P < 0.05). When participants were classified into four groups according to the CYP2A6 genotypes, group 1 ((*)1/(*)1), group 2 (heterozygotes for the (*)1 and a variant allele), group 3 (heterozygotes and homozygotes for variant alleles except for (*)4/(*)4) and group 4 ((*)4/(*)4), lung cancer risk was found to be less in subjects with the variant of CYP2A6 alleles {group 2, OR of 0.59 [95% confidence interval (CI), 0.44-0.79]; group 3, OR of 0.52 (95% CI, 0.37-0.72); group 4, OR of 0.30 (95% CI, 0.16-0.57)}. The reduced risk for lung cancer was seen more clearly in heavy smokers than in light smokers. Additional stratification analysis showed that the ORs for squamous cell carcinoma (OR of 0.07) and small cell carcinoma (OR of 0.10) were lower than that of adenocarcinoma (OR of 0.39) in group 4. These results suggest that the CYP2A6 is one of the principal determinants affecting not only smoking behavior but also susceptibility to tobacco-related lung cancer.