Lee Kuen, Cáceres Dante, Varela Nelson, Csendes D Atila, Ríos R Horacio, Quiñones S Luis
Laboratorio de Carcinogénesis Química y Farmacogenética, Programa de Farmacología Molecular y Clínica, ICBM, Universidad de Chile, Chile.
Rev Med Chil. 2006 Sep;134(9):1107-15. doi: 10.4067/s0034-98872006000900004. Epub 2006 Dec 12.
Gastric cancer (GaC) is the second cause of death by cancer in the world and one of the first causes in Chile. However, the burden of this disease shows remarkable worldwide variation probably explained by environmental and genetic factors. The role of susceptibility low penetrance genes and environmental and dietary factors in the etiology of gastric cancer is not well-known.
To analyze the possible association between CaG susceptibility, genetic (CYP1A1 and GSTM1 polymorphisms) and environmental (tobacco and alcohol) factors.
In a case-control study, we included 73 patients with a pathologically diagnosed GaC and 263 controls. DNA was extracted from peripheral blood to detect allele variants for CYP1A1 and GSTM1, using polymerase chain reactions and digestion with restriction enzymes.
There was a clear association of smoking and alcohol ingestion with GaC with odds ratios (OR) of 2.54 (95% confidence intervals (CI) of 1.45-4.46 and OR of 3.36 (95% CI 1.76-6.41), respectively. Polymorphic variants of CYP1A1 and GSTM1 had no association with GaC. However, the m2 variant of CYP1A1 significantly modifies the risk induced by tobacco or alcohol (OR 13.65; 95% CI 3.15-59.05 y 8.37; 95% CI 1.86-37.64, respectively).
Subjects that carry the m2 allelic variant of CYP1A1 and are exposed to tobacco smoke or alcohol have a significantly higher risk of developing gastric cancer.
胃癌(GaC)是全球癌症死亡的第二大原因,也是智利的主要死因之一。然而,这种疾病的负担在全球范围内存在显著差异,这可能是由环境和遗传因素造成的。低 penetrance 易感基因以及环境和饮食因素在胃癌病因中的作用尚不清楚。
分析 CaG 易感性、遗传因素(CYP1A1 和 GSTM1 多态性)与环境因素(烟草和酒精)之间的可能关联。
在一项病例对照研究中,我们纳入了 73 例经病理诊断为 GaC 的患者和 263 例对照。使用聚合酶链反应和限制性内切酶消化从外周血中提取 DNA,以检测 CYP1A1 和 GSTM1 的等位基因变体。
吸烟和饮酒与 GaC 有明显关联,比值比(OR)分别为 2.54(95%置信区间(CI)为 1.45 - 4.46)和 3.36(95%CI 为 1.76 - 6.41)。CYP1A1 和 GSTM1 的多态性变体与 GaC 无关联。然而,CYP1A1 的 m2 变体显著改变了烟草或酒精诱导的风险(OR 分别为 13.65;95%CI 为 3.15 - 59.05 和 8.37;95%CI 为 1.86 - 37.64)。
携带 CYP1A1 的 m2 等位基因变体且接触烟草烟雾或酒精的个体患胃癌的风险显著更高。