title: GSTM1 genotypes in elderly tumour-free smokers and non-smokers.
abstract: 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. Here we analysed the GSTM1 genotype frequencies in the individuals with seemingly different degrees of resistance or susceptibility to neoplasms, such as elderly tumour-free smokers and non-smokers (> or = 75-years-old), healthy middle-aged donors, and lung cancer patients. The proportion of GSTM1-deficient individuals gradually increased from elderly controls (70/157; 45%) to middle-aged ones (77/140; 55%) to lung cancer sufferers (34/58; 59%), showing the minimal estimates in elderly non-affected smokers (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 analysis has been exemplified. 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).
authors.affiliation: Group of Molecular Diagnostics, N.N. Petrov Institute of Oncology, Pesochny-2, 189646, St-Petersburg, Russia.
authors.forename: E V
authors.initials: EV
authors.lastname: Belogubova
authors.forename: A V
authors.initials: AV
authors.lastname: Togo
authors.forename: T V
authors.initials: TV
authors.lastname: Kondratieva
authors.forename: V G
authors.initials: VG
authors.lastname: Lemehov
authors.forename: K P
authors.initials: KP
authors.lastname: Hanson
authors.forename: E N
authors.initials: EN
authors.lastname: Imyanitov
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D011110:Polymorphism, Genetic; D012907:Smoking
chemical_list: D005982:Glutathione Transferase