Combined genetic polymorphism and risk for development of lung cancer

被引:68
作者
El-Zein, R
Zwischenberger, JB
Wood, TG
Abdel-Rahman, SZ
Brekelbaum, C
Au, WW
机构
[1] Univ Texas, Med Branch, Dept Prevent Med & Community Hlth, Galveston, TX 77550 USA
[2] Univ Texas, Med Branch, Dept Human Biol Chem & Genet, Galveston, TX 77550 USA
[3] Univ Texas, Med Branch, Dept Human Biol Surg, Galveston, TX 77550 USA
[4] Univ Texas, Med Branch, Sealy Ctr Mol Sci, Galveston, TX 77550 USA
关键词
genetic polymorphism; lung cancer; CYP2D6; CYP2E1; GSTM1; GSTT1; cigarette smoking; molecular epidemiology;
D O I
10.1016/S0027-5107(97)00166-8
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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 about the 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 odds ratio = 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 for the 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.
引用
收藏
页码:189 / 200
页数:12
相关论文
共 58 条
[1]   DEBRISOQUIN OXIDATION GENOTYPE AND SUSCEPTIBILITY TO LUNG-CANCER [J].
AGUNDEZ, JAG ;
MARTINEZ, C ;
LADERO, JM ;
LEDESMA, MC ;
RAMOS, JM ;
MARTIN, R ;
RODRIGUEZ, A ;
JARA, C ;
BENITEZ, J .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1994, 55 (01) :10-14
[2]   GENETIC SUSCEPTIBILITY TO LUNG-CANCER WITH SPECIAL EMPHASIS ON CYP1A1 AND GSTM1 - A STUDY ON HOST FACTORS IN RELATION TO AGE AT ONSET, GENDER AND HISTOLOGICAL CANCER TYPES [J].
ALEXANDRIE, AK ;
SUNDBERG, MI ;
SEIDEGARD, J ;
TORNLING, G ;
RANNUG, A .
CARCINOGENESIS, 1994, 15 (09) :1785-1790
[3]   Genetic polymorphism of GSTM1, CYP2E1 and CYP2D6 in Egyptian bladder cancer patients [J].
Anwar, WA ;
AbdelRahman, SZ ;
ElZein, RA ;
Mostafa, HM ;
Au, WW .
CARCINOGENESIS, 1996, 17 (09) :1923-1929
[4]   METABOLIC OXIDATION PHENOTYPES AS MARKERS FOR SUSCEPTIBILITY TO LUNG-CANCER [J].
AYESH, R ;
IDLE, JR ;
RITCHIE, JC ;
CROTHERS, MJ ;
HETZEL, MR .
NATURE, 1984, 312 (5990) :169-170
[5]   RELEVANCE OF NITROSAMINES TO HUMAN CANCER [J].
BARTSCH, H ;
MONTESANO, R .
CARCINOGENESIS, 1984, 5 (11) :1381-1393
[6]   GENETIC RISK AND CARCINOGEN EXPOSURE - A COMMON INHERITED DEFECT OF THE CARCINOGEN-METABOLISM GENE GLUTATHIONE-S-TRANSFERASE M1 (GSTM1) THAT INCREASES SUSCEPTIBILITY TO BLADDER-CANCER [J].
BELL, DA ;
TAYLOR, JA ;
PAULSON, DF ;
ROBERTSON, CN ;
MOHLER, JL ;
LUCIER, GW .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1993, 85 (14) :1159-1164
[7]   GENETIC MONITORING OF HUMAN POLYMORPHIC CANCER SUSCEPTIBILITY GENES BY POLYMERASE CHAIN-REACTION - APPLICATION TO GLUTATHIONE TRANSFERASE MU [J].
BELL, DA ;
THOMPSON, CL ;
TAYLOR, J ;
MILLER, CR ;
PERERA, F ;
HSIEH, LL ;
LUCIER, GW .
ENVIRONMENTAL HEALTH PERSPECTIVES, 1992, 98 :113-117
[8]  
BOARD PG, 1981, AM J HUM GENET, V33, P36
[9]  
Bouchardy C, 1996, CANCER RES, V56, P251
[10]  
Breslow NE, 1980, STAT METHODS CANC RE, V1, DOI DOI 10.1097/00002030-199912240-00009