GSTM1 genotypes in elderly tumour-free smokers and non-smokers

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 individual s, who succeeded to achieve a reasonably old age without a history of malig nancy, represent a distinct group of interest, which apparently can be defi ned as 'tumour-tolerant'. Focus on the genetic features of these subjects m ay significantly facilitate the research of cancer-predisposing polymorphis ms: first, a fundamental understanding of molecular mechanisms conferring t he phenomena of cancer resistance appears to be outstandingly important; se cond, it is promising to involve non-affected geriatric cohorts in the mole cular epidemiological studies as a tumour-free control of especial value. H ere we analysed the GSTM1 genotype frequencies in the individuals with seem ingly different degrees of resistance or susceptibility to neoplasms, such as elderly tumour-free smokers and non-smokers (greater than or equal to 75 -years-old), healthy middle-aged donors, and lung cancer patients. The prop ortion of GSTM1-deficient individuals gradually increased from elderly cont rols (70/157; 45%) to middle-aged ones (77/140; 55%) to lung cancer suffere rs (34/58; 59%), showing the minimal estimates in elderly non-affected smok ers (35/81; 43%) and the maximal ones in the affected non-smokers (7/7, 100 %). These data have led to the two groups of conclusions. First, the broad protective role of GSTM1 has been confirmed in this report. In particular, GSTM1-deficiency appeared to reduce the chances of entering an elderly age without a history of malignancy (OR = 0.66 (0.42-1.04); P = 0.073). Second, the efficiency of 'tumour patients versus elderly donors' comparative anal ysis has been exemplified. Indeed, the long-debated fact of overrepresentat ion of GSTM1(-) genotypes among lung cancer sufferers was clearly demonstra ted 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-aed donors (OR = 1.16 (0.63-2. 14): P = 0.641). (C) 2000 Elsevier Science Ireland Ltd. All rights reserved .