RAS ONCOGENE ACTIVATION AND OCCUPATIONAL EXPOSURES IN ACUTE MYELOID-LEUKEMIA

被引:75
作者
TAYLOR, JA
SANDLER, DP
BLOOMFIELD, CD
SHORE, DL
BALL, ED
NEUBAUER, A
MCINTYRE, OR
LIU, E
机构
[1] ROSWELL PK CANC INST,DEPT MED,BUFFALO,NY
[2] WESTAT CORP,DURHAM,NC
[3] UNIV PITTSBURGH,MED CTR,HEMATOL BONE MARROW TRANSPLANT SECT,PITTSBURGH,PA 15260
[4] UNIV N CAROLINA,SCH MED,DEPT MED,CHAPEL HILL,NC 27514
[5] DARTMOUTH COLL,HITCHCOCK MED CTR,CANC & LEUKEMIA GRP B,HANOVER,NH 03756
关键词
D O I
10.1093/jnci/84.21.1626
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Epidemiologic studies of acute myeloid leukemias (AMLs) show small increases in risk of disease associated with certain occupations and chemical exposures. Purpose: This study was designed to determine whether the presence of mutationally activated ras oncogenes in AML are associated with occupational and chemical exposures. Methods: We interviewed 62 patients with newly diagnosed AML (or their next-of-kin), all of whom were enrolled in a national multicenter clinical trial, and 630 healthy control subjects. DNA extracted from patients' pretreatment bone marrow samples was amplified by using the polymerase chain reaction and probed with allele-specific oligonucleotides for activating point mutations at the 12th, 13th, and 61st codons of three protooncogenes: H-ras (also known as HRAS), K-ras (also known as KRAS2), and N-ras (also known as NRAS). Results: Patients with ras mutation-positive AML had a higher frequency (six of 10 patients) of working 5 or more years in an a priori high-risk occupation than did patients with ras mutation-negative AML (eight of 52; odds ratio [OR] = 6.8; 95% confidence interval [CI] = 1.3-36). Patients with ras mutation-positive AML were more likely than patients with ras mutation-negative AML to have breathed chemical vapor on the job (OR = 9.1; 95% CI = 1.3-64) or to have had skin contact with chemicals OR = 6.9; 95% CI = 1.3-37). When ras-positive patients were compared with healthy control subjects, the ORs for occupation and occupational exposures remained elevated, while patients with ras mutation-negative AML showed no increased risk when compared with control subjects. Conclusion: Activation of ras proto-oncogenes may identify an etiologic subgroup of AML caused by occupation and chemical exposure. Implication: Disease etiology may be better understood if epidemiologic measures of exposure are integrated with molecular assays of the genetic defects responsible for cancer initiation and promotion.
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页码:1626 / 1632
页数:7
相关论文
共 30 条
[1]  
AHUJA HG, 1990, BLOOD, V75, P1684
[2]   RAS ONCOGENES - THEIR ROLE IN NEOPLASIA [J].
BARBACID, M .
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 1990, 20 (03) :225-235
[3]  
BARTRAM CR, 1989, LEUKEMIA, V3, P247
[4]  
BENNETT JM, 1985, ANN INTERN MED, V103, P626
[5]  
BOS JL, 1987, BLOOD, V69, P1237
[6]   AMINO-ACID SUBSTITUTIONS AT CODON-13 OF THE N-RAS ONCOGENE IN HUMAN ACUTE MYELOID-LEUKEMIA [J].
BOS, JL ;
TOKSOZ, D ;
MARSHALL, CJ ;
VERLAANDEVRIES, M ;
VEENEMAN, GH ;
VANDEREB, AJ ;
VANBOOM, JH ;
JANSSEN, JWG ;
STEENVOORDEN, ACM .
NATURE, 1985, 315 (6022) :726-730
[7]  
BROWETT PJ, 1989, ONCOGENE, V4, P1029
[8]  
COGSWELL PC, 1989, BLOOD, V74, P2629
[9]   ANALYSIS OF RAS GENE-MUTATIONS IN CHILDHOOD MYELOID-LEUKEMIA [J].
FARR, C ;
GILL, R ;
KATZ, F ;
GIBBONS, B ;
MARSHALL, CJ .
BRITISH JOURNAL OF HAEMATOLOGY, 1991, 77 (03) :323-327
[10]   ANALYSIS OF RAS GENE-MUTATIONS IN ACUTE MYELOID-LEUKEMIA BY POLYMERASE CHAIN-REACTION AND OLIGONUCLEOTIDE PROBES [J].
FARR, CJ ;
SAIKI, RK ;
ERLICH, HA ;
MCCORMICK, F ;
MARSHALL, CJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (05) :1629-1633