Factors of cancer tolerance: increased prevalence of GSTM1 proficiency in elderly tumour-free smokers and non-smokers

E.N. Imyanitov, A.V. Togo, E.V. Belogubova, V.G. Lemehov, K.P. Hanson

N.N. Petrov Institute of Oncology, St.-Petersburg, Russia

AIMS: Cancer is known to be an extremely common disease, with the life-time risks reaching close to 0.5 for men and to 0.4 for women. Hence those individuals, who succeeded to achieve a reasonably old age without a history of malignancy, represent a distinct group of interest, which apparently can be defined as “tumour-tolerant”. Focus on the genetic features of these subjects may significantly facilitate the research of cancer-predisposing polymorphisms: first, a fundamental understanding of molecular mechanisms conferring the phenomena of cancer resistance appears to be outstandingly important; second, it is promising to involve non-affected geriatric cohorts in the molecular epidemiological studies as a tumour-free control of especial value. METHODS: Here we analysed the GSTM1 genotype frequencies in the individuals with seemingly different degrees of resistance or susceptibility to pulmonary neoplasms, such as elderly tumour-free smokers and non-smokers (aged more than 75 years old), healthy middle-aged donors, and lung cancer patients. RESULTS: The proportion of GSTM1(+) individuals gradually decreased from elderly controls (87/157; 55%) to middle-aged ones (63/140; 45%) to lung cancer sufferers (24/58; 41%), showing the maximal estimates in elderly non-affected smokers (46/81; 57%) and the minimal ones in the affected non-smokers (0/7, 0%). Thus GSTM1-proficiency appeared to improve the chances of entering an elderly age without a history of malignancy (OR = 1.52 (0.96 - 2.40); P = 0.073), displaying somewhat higher impact in smoking individuals (OR = 1.61 (0.93 – 2.78); P = 0.092) than in non-smoking subjects (OR = 1.43 (0.82 – 2.50); P = 0.210). In addition, this investigation has exemplified the efficiency of «tumour patients vs. elderly donors» comparative analysis. Indeed, the long-debated fact of overrepresentation of GSTM1(-) genotypes among lung cancer sufferers was clearly demonstrated by comparison of the affected individuals to the geriatric controls (OR = 1.76 (0.96 - 3.23); P = 0.068), whereas the same patients failed to produce any convincing deviations towards the middle-aged donors (OR = 1.16 (0.63 - 2.14); P = 0.641). CONCLUSIONS: GSTM1-proficiency has a protective role against cancer. Comparison of the groups with extreme degrees of cancer predisposition is highly informative for the testing of tumor-predisposing polymorphisms.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Predictive Markers.