Molecular damage in the bronchial epithelium of current and former smokers

被引:371
作者
Wistuba, II
Lam, S
Behrens, C
Virmani, AK
Fong, KM
LeRiche, J
Samet, JM
Srivastava, S
Minna, JD
Gazdar, AF
机构
[1] UNIV TEXAS, SW MED CTR, HAMON CTR THERAPEUT ONCOL RES, NB8 106, DALLAS, TX 75235 USA
[2] PONTIFICIA UNIV CATOLICA CHILE, DEPT PATHOL, SANTIAGO, CHILE
[3] UNIV TEXAS, SW MED CTR, DEPT PATHOL, DALLAS, TX 75235 USA
[4] BRITISH COLUMBIA CANC AGCY, VANCOUVER, BC V5Z 4E6, CANADA
[5] JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, HAMON CTR THERAPEUT ONCOL RES, BALTIMORE, MD USA
[6] JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, DEPT EPIDEMIOL, BALTIMORE, MD USA
[7] NCI, BETHESDA, MD 20892 USA
[8] UNIV TEXAS, SW MED CTR, DEPT INTERNAL MED, DALLAS, TX 75235 USA
[9] UNIV TEXAS, SW MED CTR, DEPT PHARMACOL, DALLAS, TX 75235 USA
来源
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | 1997年 / 89卷 / 18期
关键词
D O I
10.1093/jnci/89.18.1366
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Most lung cancers are attributed to smoking, These cancers have been associated with multiple genetic alterations and with the presence of preneoplastic bronchial lesions, In view of such associations, we evaluated the status of specific chromosomal loci in histologically normal and abnormal bronchial biopsy specimens from current and former smokers and specimens from nonsmokers, Methods: Multiple biopsy specimens were obtained from 18 current smokers, 24 former smokers, and 21 nonsmokers, Polymerase chain reaction-based assays involving 15 polymorphic microsatellite DNA markers were used to examine eight chromosomal regions for genetic changes (loss of heterozygosity [LOH] and microsatellite alterations), Results: LOH and microsatellite alterations were observed in biopsy specimens from both current and former smokers, but no statistically significant differences were observed between the two groups. Among individuals with a history of smoking, 86% demonstrated LOH in one or more biopsy specimens, and 24% showed LOH in all biopsy specimens, About half of the histologically normal specimens from smokers showed LOH, but the frequency of LOH and the severity of histologic change did not correspond until the carcinoma in situ stage, A subset of biopsy specimens from smokers that exhibited either normal or preneoplastic histology showed LOH at multiple chromosomal sites, a phenomenon frequently observed in carcinoma in situ and invasive cancer, LOH on chromosomes 3p and 9p was more frequent than LOH on chromosomes 5q, 17p (17p13; TP53 gene), and 13q (13q14; retinoblastoma gene), Microsatellite alterations were detected in 64% of the smokers, No genetic alterations were detected in nonsmokers, Conclusions: Genetic changes similar to those found in lung cancers can be detected in the nonmalignant bronchial epithelium of current and former smokers and may persist for many years after smoking cessation.
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收藏
页码:1366 / 1373
页数:8
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