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Titolo:
COMBINED GENETIC-POLYMORPHISM AND RISK FOR DEVELOPMENT OF LUNG-CANCER
Autore:
ELZEIN R; ZWISCHENBERGER JB; WOOD TG; ABDELRAHMAN SZ; BREKELBAUM C; AU WW;
Indirizzi:
UNIV TEXAS,MED BRANCH,DEPT PREVENT MED & COMMUNITY HLTH,2-102 EWING HALL,700 HARBORSIDE DR GALVESTON TX 77550 UNIV TEXAS,MED BRANCH,DEPT PREVENT MED & COMMUNITY HLTH GALVESTON TX 77550 UNIV TEXAS,MED BRANCH,DEPT HUMAN BIOL CHEM & GENET GALVESTON TX 77550 UNIV TEXAS,MED BRANCH,DEPT HUMAN BIOL SURG GALVESTON TX 77550 UNIV TEXAS,MED BRANCH,SEALY CTR MOL SCI GALVESTON TX 77550
Titolo Testata:
Mutation research. Fundamental and molecular mechanisms of mutagenesis
fascicolo: 2, volume: 381, anno: 1997,
pagine: 189 - 200
SICI:
1386-1964(1997)381:2<189:CGARFD>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
GLUTATHIONE-S-TRANSFERASE; TRANS-STILBENE OXIDE; CLASS-MU; CARCINOGEN-METABOLISM; POOR METABOLIZERS; HUMAN-LEUKOCYTES; BLADDER-CANCER; CYP2D6 GENE; SUSCEPTIBILITY; DEBRISOQUINE;
Keywords:
GENETIC POLYMORPHISM; LUNG CANCER; CYP2D6; CYP2E1; GSTM1; GSTT1; CIGARETTE SMOKING; MOLECULAR EPIDEMIOLOGY;
Tipo documento:
Article
Natura:
Periodico
Citazioni:
58
Recensione:
Indirizzi per estratti:
Citazione:
R. Elzein et al., "COMBINED GENETIC-POLYMORPHISM AND RISK FOR DEVELOPMENT OF LUNG-CANCER", Mutation research. Fundamental and molecular mechanisms of mutagenesis, 381(2), 1997, pp. 189-200

Abstract

Susceptibility to lung cancer has been shown to be modulated by host specific factors. Inheritance of different polymorphic cytochrome P450s (CYPs) and the glutathione S-transferases (GSTs) which affect metabolism of environmental toxicants may play a key role in individual susceptibility. Although individual polymorphic genes have been reported to be associated with development of lung cancer, little is known aboutthe combined effects of several genes in carcinogenesis. From our study of 54 lung cancer patients and 50 matched controls, we observed that a combination of several versions of 'unfavorable' metabolizing genes (CYP2D6, CYP2E1, GSTM1 and GSTT1) is strongly associated with lung cancer. The relative risk for the different combinations of these genotypes ranged between 1.3 and 14, with higher risk involving the activating genes. The duration and intensity of heavy smoking (expressed in pack-years) are the most important determinant for the development of lung cancer, For example, the estimated risk for development of lung cancer associated with smoking > 30 pack-years is represented by an oddsratio = 6.65; 95% CL = 2.3-19.9 irrespective of an individual's genotype, whereas for smoking between > 30 and < 50 pack-years, odds ratio = 4.5; 95% CL = 1.37-15; and for smoking > 50 pack-years, odds ratio =30; 95% CL = 5.7-114. On the other hand, smoking of less than 30 pack-years is associated with an increased risk in the presence of the polymorphic genes (odds ratio = 2.5; 95% CL = 0.32-54). The results of our study indicate that the inheritance of multiple 'unfavorable' genotypes, especially activating genes, is a crucial predisposing factor forthe development of lung cancer from cigarette smoking. In addition, the genes may cause moderate smokers who would normally outlive the deleterious effects of smoking to develop lung cancer. The information can therefore be used to target individuals for prevention of health problems. (C) 1997 Elsevier Science B.V.

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Documento generato il 26/01/20 alle ore 10:09:23