p53 mutation spectra for squamous cell carcinomas at different levels of human bronchial branches

• Published in: International journal of cancer 2006-08, Vol.119 (3), p.501-507
• Main Authors: Shimmyo, Takuo, Hashimoto, Takehisa, Kobayashi, Yasuhito, Miyagi, Youhei, Ishikawa, Yuichi, Nakagawa, Ken, Osada, Hiroaki, Tsuchiya, Eiju
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Bronchi - pathology; Carcinoma, Squamous Cell - etiology; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; CpG Islands - genetics; DNA Mutational Analysis - methods; Female; Gene Frequency; Humans; Lung Neoplasms - etiology; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Medical sciences; Middle Aged; Mutation; p53; Pneumology; Point Mutation; Smoking - adverse effects; squamous cell lung carcinoma; tumor location; Tumor Suppressor Protein p53 - genetics; Tumors; Tumors of the respiratory system and mediastinum
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.21877

The question of whether squamous cell carcinomas (SCCs) arising in different sites of lung are caused by different etiological factors is of obvious importance for prevention, early detection and effective treatment. We here subclassified a large series of resected SCCs (74 cases) into 3 tumor‐sites, central (main to segmental bronchi), intermediate (subsegmental to sub‐subsegmental) and peripheral (distal to sub‐subsegmental bronchi), and examined relationships with p53 mutational spectra and smoking history to provide clues to etiological factors. The rate for G→A transitions at CpG sites considered to be caused by endogenous mechanism was higher in central (40%) than in intermediate (0%) and peripheral (14%) lesions, in spite of highest percentage of heavy smokers. In contrast, G→T transversions associated with tobacco smoke carcinogens were most frequent (50%) in the intermediate location, although proportions of heavy smoker's ratio were the same among the locations when confined to p53 mutation cases. In the periphery, other mutations were highest (67%) compared with 33 and 50% in the central and intermediate regions, respectively. Thus, different etiological factors may be playing causal roles in the development of SCCs in different locations of bronchial tree. Furthermore, the results suggest that more extensive study of the influence of tobacco smoke carcinogens on endogenous mechanisms is warranted. © 2006 Wiley‐Liss, Inc.