Combined effects of asbestos and cigarette smoke on the development of lung adenocarcinoma: Different carcinogens may cause different genomic changes

Inamura,Kentaro; Ninomiya,Hironori; Nomura,Kimie; Tsuchiya,Eiju; Satoh,Yukitoshi; Okumura,Sakae; Nakagawa,Ken; Takata,Ayako; Kohyama,Norihiko; Ishikawa,Yuichi

doi:10.3892/or.2014.3263

Combined effects of asbestos and cigarette smoke on the development of lung adenocarcinoma: Different carcinogens may cause different genomic changes

Authors:
- Kentaro Inamura
- Hironori Ninomiya
- Kimie Nomura
- Eiju Tsuchiya
- Yukitoshi Satoh
- Sakae Okumura
- Ken Nakagawa
- Ayako Takata
- Norihiko Kohyama
- Yuichi Ishikawa
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Affiliations: Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research (JFCR), Koto-ku, Tokyo 135‑8550, Japan, Department of Thoracic Surgery, Kitasato University School of Medicine, Sagamihara, Kanagawa 228‑8555, Japan, Department of Thoracic Surgery, The Cancer Institute Hospital, JFCR, Koto-ku, Tokyo 135‑8550, Japan, Department of Preventive Medicine, St. Marianna University School of Medicine, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan, Faculty of Economics, Toyo University, Bunkyo-ku, Tokyo 12-8608, Japan
Published online on: June 13, 2014 https://doi.org/10.3892/or.2014.3263
Pages: 475-482
Copyright: © Inamura et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

The carcinogens in cigarette smoke are distinct from asbestos. However, an understanding of their differential effects on lung adenocarcinoma development remains elusive. We investigated loss of heterozygosity (LOH) and the p53 mutation in 132 lung adenocarcinomas, for which asbestos body burden (AB; in numbers per gram of dry lung) was measured using adjacent normal lung. All cases were classified into 9 groups based on a matrix of cumulative smoking (CS in pack‑years; CS=0, 00 groups, LOH frequency increased as AB and/or CS was elevated and was significantly higher in the ≥1,000 AB, ≥25 CS group (p=0.032). p53 mutation frequency was the lowest in the AB=0, CS=0 group, increased as AB and/or CS rose, and was significantly higher in the ≥1,000 AB, ≥25 CS group (p=0.039). p53 mutations characteristic of smoking were frequently observed in the CS>0 groups contrary to non-specific mutations in the CS=0, AB>0 groups. Combined effects of asbestos and smoking were suggested by LOH and p53 analyses. Sole exposure to asbestos did not increase LOH frequency but increased non‑specific p53 mutations. These findings indicate that the major carcinogenic mechanism of asbestos may be tumor promotion, acting in an additive or synergistic manner, contributing to the genotoxic effect of smoking. Since this study was based on a general cancer center's experience, the limited sample size did not permit the consideration that the result was conclusive. Further investigation with a large sample size is needed to establish the mechanism of asbestos-induced lung carcinogenesis.

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