GENETIC SUSCEPTIBILITY TO LUNG-CANCER WITH SPECIAL EMPHASIS ON CYP1A1 AND GSTM1 - A STUDY ON HOST FACTORS IN RELATION TO AGE AT ONSET, GENDER AND HISTOLOGICAL CANCER TYPES
GENETIC SUSCEPTIBILITY TO LUNG-CANCER WITH SPECIAL EMPHASIS ON CYP1A1 AND GSTM1 - A STUDY ON HOST FACTORS IN RELATION TO AGE AT ONSET, GENDER AND HISTOLOGICAL CANCER TYPES
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DOI：
10.1093/carcin/15.9.1785
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发表时间：
1994-09-01
期刊：
影响因子：
4.7
通讯作者：
RANNUG, A
中科院分区：
文献类型：
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作者：
ALEXANDRIE, AK;SUNDBERG, MI;RANNUG, A
基于遗传的代谢差异，与细胞色素P450（CYP）1A 1基因的MspI限制性位点和Ile-Val多态性以及谷胱甘肽转移酶mu类（GSTM 1）的无效基因型相关，已被报道与肺癌易感性相关。本研究旨在建立瑞典CYP 1A 1和GSTM 1多态性基因型的频率，评估瑞典肺癌患者中与肺癌风险较高相关的基因型的可能发生率增加，并尝试对多个风险等位基因携带者进行联合风险估计。在健康对照组中，所有66岁以下的受试者中，53%（174/329）的受试者为GSTM 1（-）基因型，而在医院对照组中，49%（39/79）的受试者为GSTM 1（-）基因型。在所调查的肺癌患者中，该基因型的检出率为56%（165/296），在66岁以前确诊的肺癌患者中，该基因型的缺失率为60%（78/131）。GSTM 1（-）基因型在66岁以前诊断为腺癌（63%，29/46）、小细胞癌（72%，21/29）和女性鳞癌（79%，15/19）患者中的比例最高。CYP 1A 1等位基因变异在肺癌患者和对照组中分布均匀。然而，MspI位点的m1/m2和m2/m2基因型以及Ile/瓦尔基因型在鳞状细胞癌患者中略微过度表达。在66岁以前确诊的鳞状细胞癌患者中，28%（10/36）的患者存在m1/m2基因型，而在16%（52/329）的健康对照组中观察到相同的基因型。在66岁以前诊断的同时携带GSTM 1（-）和m2等位基因的患者具有鳞状细胞癌的联合风险（OR = 3.0，95%CI = 1.2-7.2）。
Genetically based differences in metabolism, related to MspI restriction site and Ile-Val polymorphisms of the cytochrome P450 (CYP) 1A1 gene and the null genotype of glutathione transferase class mu (GSTM1), have been reported to be associated with lung cancer susceptibility. The present study was set up to establish the frequencies of the polymorphic genotypes of CYP1A1 and GSTM1 in Sweden, to evaluate a possible increased incidence of the genotypes associated with higher lung cancer risks among Swedish lung cancer patients and to try to make a combined risk estimate for carriers of multiple risk alleles. In a healthy control group, all under 66 years of age, 53% (174/329) of the subjects were of the GSTM1(-) genotype, while in a hospital control group 49% (39/79) carried the GSTM1(-) genotype. In the investigated lung cancer patients this genotype was found in 56% (165/296) and among those patients diagnosed before 66 years of age the deficient genotype was found in 60% (78/131). The highest proportion of the GSTM1(-) genotype was found in patients diagnosed with adenocarcinoma (63%, 29/46) and small cell carcinoma (72%, 21/29) before 66 years of age and among female squamous cell carcinoma patients (79%, 15/19). The allelic variants in CYP1A1 were equally distributed in lung cancer patients and controls. The m1/m2 and m2/m2 genotypes of the MspI site and the Ile/Val genotype were, however, slightly over-represented in squamous cell carcinoma patients. Among patients with squamous cell carcinoma diagnosed before 66 years of age the m1/m2 genotype was found in 28% (10/36), whereas the same genotype was observed in 16% (52/329) of healthy control subjects. A combined risk of squamous cell carcinoma was indicated for patients, diagnosed before 66 years of age, carrying both GSTM1(-) and m2 alleles (OR = 3.0, 95% CI = 1.2-7.2).