Belogubova Evgeniya V, Togo Alexandr V, Karpova Maria B, Kuligina Ekatherina Sh, Buslova Konstantin G, Ulibina Julia M, Lemehov Vladimir G, Romanenko Sergey M, Shutkin Vladimir A, Hanson Kaido P, Hirvonen Ari, Imyanitov Evgeny N
Group of Molecular Diagnostics, N.N. Petrov Institute of Oncology, Pesochny-2, 197758, St.-Petersburg 197758, Russia.
Lung Cancer. 2004 Mar;43(3):259-66. doi: 10.1016/j.lungcan.2003.08.019.
We applied an alternative approach to assess the controversial evidence for the role of GSTM1 and GSTT1 deficiencies (null genotypes) in cancer susceptibility. In this study setting, the prevalence of GSTM1 and GSTT1 null genotypes in the lung cancer patients (LCs, n = 167) were compared with those in the group of putatively cancer resistant individuals, i.e. elderly tumor-free donors (EDs, n = 324). Healthy middle-aged donors (HDs, n = 339) were used as another comparison group. Our results support the previous conclusions of a modest protective effect associated with presence of at least one functional copy of GSTM1 gene; the prevalence of GSTM1 deficiency in LCs (54%) did not differ from that observed in HDs (54%), but showed a significant increase when compared with EDs (45%) (OR = 1.46, 95% CI = 1.00-2.12). Furthermore, in agreement with mechanistic considerations, the GSTM1 null genotypes were more prevalent in squamous cell carcinoma patients (58%) and in lung cancer patients with seemingly low cumulative carcinogen exposure dose (non-smokers: 63%; patients aged below 50 years: 76%). Contrary to GSTM1, no significant effect in the lung cancer proneness was observed for the GSTT1 genotypes. The results of this study are thus in good agreement with the body of literature data, including several published meta-analyses. Consequently, the suggested study design involving additional "cancer resistant" group of non-affected subjects appears to provide highly demonstrative data and to be well suited for pilot investigations and for resolving controversial issues.
我们采用了另一种方法来评估关于谷胱甘肽S-转移酶M1（GSTM1）和谷胱甘肽S-转移酶T1（GSTT1）缺陷（无效基因型）在癌症易感性中作用的有争议证据。在本研究中，将肺癌患者（LCs，n = 167）中GSTM1和GSTT1无效基因型的患病率与假定的癌症抗性个体组，即老年无肿瘤供体（EDs，n = 324）中的患病率进行了比较。健康中年供体（HDs，n = 339）用作另一个比较组。我们的结果支持了先前关于至少有一个GSTM1基因功能拷贝存在具有适度保护作用的结论；肺癌患者中GSTM1缺陷的患病率（54%）与健康中年供体中观察到的患病率（54%）没有差异，但与老年无肿瘤供体相比显著增加（老年无肿瘤供体为45%）（比值比 = 1.46，95%置信区间 = 1.00 - 2.12）。此外，与机制考虑一致，GSTM1无效基因型在鳞状细胞癌患者中更常见（58%），在累积致癌物暴露剂量似乎较低的肺癌患者中也更常见（非吸烟者：63%；50岁以下患者：76%）。与GSTM1相反，未观察到GSTT1基因型对肺癌易感性有显著影响。因此，本研究结果与包括几项已发表的荟萃分析在内的文献数据非常一致。因此，建议的研究设计包括额外的未受影响的“癌症抗性”组，似乎能提供极具说服力的数据，非常适合进行初步调查和解决有争议的问题。
