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H. Takeshima

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    P1.02 - Biology/Pathology (ID 614)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P1.02-009 - Accumulation of Mutations in Background Normal Lung Tissue Constitutes a Major Lung Cancer Risk (ID 9240)

      09:30 - 16:00  |  Author(s): H. Takeshima

      • Abstract

      Accumulation of mutations in normal-appearing lung tissue is believed to be important for development of lung cancer, and to be heavily influenced by smoking. However, their very low levels have been hampering their measurement, and their links with cancer risk and smoking history have not been demonstrated. To overcome this limitation, we recently developed a novel method that can measure levels of somatic mutations at 10[-6]/bp levels [Yamashita et al., Cancer Lett, online].

      Eleven healthy lung tissues (Group1:G1) were collected from the normal lungs of metastatic lung cancer patients without smoking history, and 11 exposed lung tissues (Group2:G2) were collected from those with smoking history. 11 high-risk lung tissues (Group3:G3) were collected from the lungs of lung cancer patients with smoking history. A sequence library (15,552 bases of 291 regions of 55 cancer-related genes) was prepared by multiplex PCR using 100 DNA molecules, and was sequenced using a next generation sequencer.

      The accumulation levels of mutations were significantly higher in G3 (2.7 ± 0.8×10[-5] mutations/base) than those in G1 (1.8 ± 0.5×10[-5] mutations/base) (p = 0.0189). The accumulation appeared to be associated with smoking history (OR = 3.2; 95 % CI = 0.54–18.98), and the C>T mutation, a signature reported in cancer tissues [Alexandrov et al., Science, 354:2016], was significantly more frequent in G2 than in G1. The GCC>GTC and CCC>CTC mutations, a signature of exposure to the nitrosamines contained in tobacco smoke, were significantly more frequent in G2 and G3.

      The accumulation level of mutations was increased in exposed lung tissues, and the mutation accumulation was associated with cancer risk.