Relationship between the loss of heterozygosity and tobacco smoking in pulmonary adenocarcinoma.
A loss of heterozygosity (LOH) is a major cause of lung carcinogenesis, and it is considered to be related to tobacco smoking in central type lung cancer. We investigated the relationship between LOH in lung adenocarcinoma and tobacco smoking. In a consecutive series of 50 patients with lung adenocarcinoma who underwent a surgical resection, cancer tissue specimens and corresponding normal peripheral lung and central bronchial tissue specimens were analyzed for LOH at the regions of D3S1234 (FHIT), D3S1300 (FHIT), D9S171 (CDKN2), and D17S796 (p53) by polymerase chain reaction using four fluorescence-labeled dinucleotide markers. To examine how cells are influenced by smoking, the A549 cell line was exposed to benzo[a]pyrene (B[a]P) for 24 weeks and then was subjected to the above analysis. The LOH in cancer tissue was thus detected in four (17%) patients at D3S1234, six (14%) at D3S1300, and seven (18%) at D17S796, but no LOH was detected in any normal tissue specimens. The incidence of LOHs in cancer tissue specimens from active smokers was 21% at D3S1234, 11% at D3S1300, and 19% at D17S796, whereas that of LOHs from nonactive smokers was 0% at D3S1234, 19% at D3S1300, and 14% at D17S796. Analyzing the relationship between the pack-year index and the presence of LOH, a significant difference was found among the active smokers. Besides, in the A549 cell line exposed to B[a]P, LOH was de novo detected in one (D2S123) of the nine regions examined. The incidence of LOH could be influenced by tobacco smoking in lung adenocarcinoma, thus suggesting the presence of an important event in the carcinogenesis of this disease.
Yohena
Tomofumi
T
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Yoshino
Ichiro
I
Takenaka
Tomoyoshi
T
Ohba
Taro
T
Kouso
Hidenori
H
Osoegawa
Atsushi
A
Hamatake
Motoharu
M
Oda
Shinya
S
Kuniyoshi
Yukio
Y
Maehara
Yoshihiko
Y
D000230:Adenocarcinoma / Q000209:etiology* / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001564:Benzo(a)pyrene / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000209:etiology* / Q000235:genetics; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity / Q000187:drug effects / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D012907:Smoking / Q000009:adverse effects*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects
D014028:Tobacco Smoke Pollution; D001564:Benzo(a)pyrene