Polymorphisms in metabolic genes, their combination and interaction with tobacco smoke and alcohol consumption and risk of gastric cancer: a case-control study in an Italian population.
Polymorphisms in metabolic genes, their combination and interaction with tobacco smoke and alcohol consumption and risk of gastric cancer: a case-control study in an Italian population.
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DOI：
10.1186/1471-2407-7-206
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发表时间：
2007-11-08
期刊：
影响因子：
3.8
通讯作者：
Ricciardi G
中科院分区：
文献类型：
--
作者：
Boccia S;Sayed-Tabatabaei FA;Persiani R;Gianfagna F;Rausei S;Arzani D;La Greca A;D'Ugo D;La Torre G;van Duijn CM;Ricciardi G
在一个意大利人群中，研究了选定的代谢遗传多态的分布以及潜在的基因-基因和基因-环境相互作用与胃癌风险的关系。对107例受试者和2 5 4例住院对照进行了CYP1A1、CYP2E1、meh、GSTM1、GSTT1、NAT2和SULT1A1基因分型。对EPHX1基因外显子3和4以及CYP2E1RsaI(*5个等位基因)和CYP2E1Drai(*5A或*6个等位基因)进行单倍型分析。用异质性检验检验烟酒对效应的影响，用基因-基因互作分析用归因比(AP)来衡量生物互作。GSTT1基因缺失(OR=2.10，95%CI：1.27~3.44)和SULT1A1His/His基因(OR=2.46，95%CI：1.03~5.90)与胃癌发生相关。单倍型分布在病例组和对照组之间无明显差异。首次发现携带CYP2E1*6变异等位基因的个体如果饮酒(OR=3.7；95%CI：1.45~9.37)与从不饮酒者(OR=0.18；95%CI：0.22~1.46)相比(两种估计的异质性p值=0.001)。同样，SULT1A1变异基因型的影响仅限于吸烟者，吸烟者携带HIS等位基因的OR值为2.58(95%CI：1.27~5.25)，不吸烟者携带HIS等位基因的OR值为0.86(95%CI：0.45~1.64)(两种估计值的异质性p值=0.03)。基因-基因交互作用分析显示，GSTT1缺失和NAT2慢乙酰化结合的个体患胃癌的风险增加，OR为3.00(95%CI：1.52~5.93)，AP为52%。在这个意大利人群中，GSTT1、SULT1A1和NAT2的多态似乎调节了个体对胃癌的易感性，特别是当存在不止一个不利的基因时，或者当结合吸烟时。饮酒者携带CYP2E1*5A或*6等位基因的风险增加，还需要更大规模的前瞻性研究来证实。
The distribution and the potential gene-gene and gene-environment interaction of selected metabolic genetic polymorphisms was investigated in relation to gastric cancer risk in an Italian population. One hundred and seven cases and 254 hospital controls, matched by age and gender, were genotyped for CYP1A1, CYP2E1, mEH, GSTM1, GSTT1, NAT2 and SULT1A1 polymorphisms. Haplotype analysis was performed for EPHX1 exons 3 and 4, as well as CYP2E1 RsaI (*5 alleles) and CYP2E1 DraI (*5A or *6 alleles). The effect modification by alcohol and cigarette smoking was tested with the heterogeneity test, while the attributable proportion (AP) was used to measure the biological interaction from the gene-gene interaction analysis. Gastric cancer risk was found to be associated with the inheritance of GSTT1 null genotype (OR = 2.10, 95%CI: 1.27–3.44) and the SULT1A1 His/His genotype (OR = 2.46, 95%CI: 1.03–5.90). No differences were observed for the haplotype distributions among cases and controls. For the first time an increased risk was detected among individuals carrying the *6 variant allele of CYP2E1 if ever-drinkers (OR = 3.70; 95%CI: 1.45–9.37) with respect to never-drinkers (OR = 0.18; 95% CI: 0.22–1.46) (p value of heterogeneity among the two estimates = 0.001). Similarly, the effect of SULT1A1 variant genotype resulted restricted to ever-smokers, with an OR of 2.58 (95%CI: 1.27–5.25) for the carriers of His allele among smokers, and an OR of 0.86 (95%CI: 0.45–1.64) among never-smokers (p value of heterogeneity among the two estimates = 0.03). The gene-gene interaction analyses demonstrated that individuals with combined GSTT1 null and NAT2 slow acetylators had an additional increased risk of gastric cancer, with an OR of 3.00 (95%CI: 1.52–5.93) and an AP of 52%. GSTT1, SULT1A1 and NAT2 polymorphisms appear to modulate individual's susceptibility to gastric cancer in this Italian population, particularly when more than one unfavourable genotype is present, or when combined with cigarette smoke. The increased risk for the carriers of CYP2E1*5A or *6 alleles among drinkers need to be confirmed by larger prospective studies.