To-Figueras J, Gene M, Gomez-Catalan J, Galan C, Firvida J, Fuentes M, Rodamilans M, Huguet E, Estape J, Corbella J
Hospital Clinic i Provincial, School of Medicine, University of Barcelona, Catalonia, Spain.
Cancer Epidemiol Biomarkers Prev. 1996 May;5(5):337-42.
Several polymorphic genes have been reported to be possibly involved in modifying lung cancer risk in smokers. The gene GSTM1 is frequently deleted in human populations, and the null genotype has been reported to be a risk factor for developing lung carcinoma. A germline polymorphism of p53 with a single-base change at codon 72 that causes an amino acid replacement of arginine (Arg; CGC) by proline (PRO; CCC) has also been reported to be associated with cancer susceptibility in a Japanese population. Both polymorphisms were genotyped by PCR in a northwestern Mediterranean healthy population (n = 147) and in a group of lung cancer patients (n = 139). The results showed that the frequency of the GSTM1 null genotype was higher in the lung cancer patients compared to the controls [odds ratio (OR), 1.57; 95% confidence interval (CI), 0.99-2.51]. The histological subtypes most clearly modified were small cell carcinoma (OR, 1.89; CI, 0.97-3.65) and adenocarcinoma (OR, 1.93; CI, 0.90-4.14). The null GSTM1 genotype was more frequent among those cancer patients who were medium/ light smokers (< or = 50 pack-years) and in those who showed an onset of the disease at a more advanced age. The study of the p53 polymorphism in the healthy population showed allele frequencies of 0.79 (Arg) and 0.21 (Pro). The frequencies found in the lung cancer patients were statistically similar. Both polymorphisms were studied together, and the relative risk of the combination null GSTM1 and Pro/Pro or Arg/Pro genotypes was calculated taking the combination of GTSM1 + together with Arq/Arg as a baseline. The OR found (1.97; CI, 1.03-3.73) suggests that the Pro allele of the p53 germline polymorphism may slightly increase the risk fo the GSTM1 null genotype among smokers.
据报道，有几个多态性基因可能参与改变吸烟者患肺癌的风险。基因GSTM1在人群中经常缺失，据报道，无效基因型是患肺癌的一个风险因素。据报道，p53基因的一种种系多态性在密码子72处有一个单碱基变化，导致精氨酸（Arg；CGC）被脯氨酸（Pro；CCC）取代，这也与日本人群的癌症易感性有关。在地中海西北部的健康人群（n=147）和一组肺癌患者（n=139）中，通过聚合酶链反应对这两种多态性进行了基因分型。结果显示，与对照组相比，肺癌患者中GSTM1无效基因型的频率更高[优势比（OR），1.57；95%置信区间（CI），0.99 - 2.51]。受影响最明显的组织学亚型是小细胞癌（OR，1.89；CI，0.97 - 3.65）和腺癌（OR，1.93；CI，0.90 - 4.14）。无效GSTM1基因型在中度/轻度吸烟者（<或=50包年）以及发病年龄较大的癌症患者中更为常见。对健康人群中p53多态性的研究显示，等位基因频率为0.79（Arg）和0.21（Pro）。在肺癌患者中发现的频率在统计学上相似。对这两种多态性进行了联合研究，并以GTSM1 + 与Arq/Arg的组合为基线，计算了无效GSTM1与Pro/Pro或Arg/Pro基因型组合的相对风险。发现的OR（1.97；CI，1.03 - 3.73）表明，p53种系多态性的Pro等位基因可能会略微增加吸烟者中GSTM1无效基因型的风险。
