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Tumour mutational burden LCINS generally have a markedly lower TMB (measured as non-synonymous mutations per megabase (mut/Mb)) in coding and non-coding regions compared to smoking-related lung cancers, with early studies suggesting as much as a tenfold difference 131 and a doseresponse relationship between TMB and pack-years 132 (Table 1)

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in the latter, the damage is accumulated much more slowly, with effects lying dormant for years

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