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
.