DEBRISOQUIN OXIDATION GENOTYPE AND SUSCEPTIBILITY TO LUNG-CANCER

被引:61
作者
AGUNDEZ, JAG
MARTINEZ, C
LADERO, JM
LEDESMA, MC
RAMOS, JM
MARTIN, R
RODRIGUEZ, A
JARA, C
BENITEZ, J
机构
[1] UNIV EXTREMADURA, FAC MED, SCH MED, DEPT PHARMACOL, E-06071 BADAJOZ, SPAIN
[2] UNIV COMPLUTENSE, SCH MED, DEPT INTERNAL MED, E-28040 MADRID, SPAIN
关键词
D O I
10.1038/clpt.1994.3
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The association between the polymorphism of the cytochrome P450 debrisoquin hydroxylase (C Upsilon P2D6) and lung cancer is controversial. Previous reports suggested a link between C Upsilon P2D6 phenotype and lung cancer, with poor metabolizers having reduced susceptibility. Nevertheless, negative findings have also been published. By using allele-specific amplification, we have studied the frequency of four (C Upsilon P2D6 (wild type and mutant) alleles in 89 patients with histologically proved bronchogenic carcinoma and in 98 healthy volunteers. Our findings confirm that poor metabolizers are underpresented among patients with lung cancer because of a different genetic background. Our findings also reveal that the rare C Upsilon P2D6(C) mutant allele is sixfold more frequent among patients with lung cancer (p < 0.0005). This suggests that the C Upsilon P2D6(C) allele could be considered as an additional risk factor because carriers could have higher susceptibility to the development of lung cancer.
引用
收藏
页码:10 / 14
页数:5
相关论文
共 24 条
[1]   HYDROXYLATION POLYMORPHISMS OF DEBRISOQUINE AND MEPHENYTOIN IN EUROPEAN POPULATIONS [J].
ALVAN, G ;
BECHTEL, P ;
ISELIUS, L ;
GUNDERTREMY, U .
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 1990, 39 (06) :533-537
[2]   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
[3]   POLYMORPHIC OXIDATION OF DEBRISOQUINE IN LUNG-CANCER PATIENTS [J].
BENITEZ, J ;
LADERO, JM ;
JARA, C ;
CARRILLO, JA ;
COBALEDA, J ;
LLERENA, A ;
VARGAS, E ;
MUNOZ, JJ .
EUROPEAN JOURNAL OF CANCER, 1991, 27 (02) :158-161
[4]   DEBRISOQUINE OXIDATION POLYMORPHISM - PHENOTYPIC CONSEQUENCES OF A 3-BASE-PAIR DELETION IN EXON 5 OF THE CYP2D6 GENE [J].
BROLY, F ;
MEYER, UA .
PHARMACOGENETICS, 1993, 3 (03) :123-130
[5]   DEBRISOQUINE SPARTEINE HYDROXYLATION GENOTYPE AND PHENOTYPE - ANALYSIS OF COMMON MUTATIONS AND ALLELES OF CYP2D6 IN A EUROPEAN POPULATION [J].
BROLY, F ;
GAEDIGK, A ;
HEIM, M ;
EICHELBAUM, M ;
MORIKE, K ;
MEYER, UA .
DNA AND CELL BIOLOGY, 1991, 10 (08) :545-558
[6]  
CAPORASO N, 1989, CANCER RES, V49, P3675
[7]   LUNG-CANCER AND THE DEBRISOQUINE METABOLIC PHENOTYPE [J].
CAPORASO, NE ;
TUCKER, MA ;
HOOVER, RN ;
HAYES, RB ;
PICKLE, LW ;
ISSAQ, HJ ;
MUSCHIK, GM ;
GREENGALLO, L ;
BUIVYS, D ;
AISNER, S ;
RESAU, JH ;
TRUMP, BF ;
TOLLERUD, D ;
WESTON, A ;
HARRIS, CC .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1990, 82 (15) :1264-1272
[8]   LACK OF A RELATIONSHIP BETWEEN THE POLYMORPHISM OF DEBRISOQUINE OXIDATION AND LUNG-CANCER [J].
DUCHE, JC ;
JOANNE, C ;
BARRE, J ;
DECREMOUX, H ;
DALPHIN, JC ;
DEPIERRE, A ;
BROCHARD, P ;
TILLEMENT, JP ;
BECHTEL, P .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1991, 31 (05) :533-536
[9]   IDENTIFICATION OF THE PRIMARY GENE DEFECT AT THE CYTOCHROME-P450 CYP2D LOCUS [J].
GOUGH, AC ;
MILES, JS ;
SPURR, NK ;
MOSS, JE ;
GAEDIGK, A ;
EICHELBAUM, M ;
WOLF, CR .
NATURE, 1990, 347 (6295) :773-776
[10]   PREDICTION OF PHENOTYPE FOR ACETYLATION AND FOR DEBRISOQUINE HYDROXYLATION BY DNA-TESTS IN HEALTHY-HUMAN VOLUNTEERS [J].
GRAF, T ;
BROLY, F ;
HOFFMANN, F ;
PROBST, M ;
MEYER, UA ;
HOWALD, H .
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 1992, 43 (04) :399-403