Abstract 3245: The interplay between patient´s features and mutational processes in tobacco related cancers

Abstract

Abstract Background: There is a complex interplay between smoking and patient demographics in the emergence and development of cancer. We vetted the possible relationship between gender, race and age with mutational processes operating on aerodigestive tract cancers, known to be highly associated to tobacco. Methods: We used an empirical Bayesian approach to identify genomic patterns that lead to mutational processes in head and neck, esophageal, and lung cancers from TCGA database followed by confirmation in independent cohorts (cBioPortal). Results: After confronting clinical information and smoking-habits to molecular findings in those cancers, we identified imprints of different mutational processes in a disease-, gender- and race-specific fashion. Black and female patients - despite their lower tobacco consumption in comparison to whites or males - had tumors with the highest enrichment for tobacco-induced DNA damage. The relevance of mutational signatures related to aging varied across race and gender and were independent from chronological age. The activity of smoking signature was different according to disease histotype, and stage. tumors of never-smoker lung cancer patients showed tobacco-specific mutational signatures, which could suggest the influence of second-hand smoking. Patients with tumors enriched for the smoking mutational signature presented longer survival, whereas those with ageing-enriched signature had poorer prognosis. Conclusions: Mutational processes may unravel connections between patient features and tumorigenesis, particular to race, gender, and tumor type. Therefore, it is paramount to assess those details with greater granularity in every effort of personalized medicine either in preventive or therapeutic approaches. Citation Format: João Paulo da Silveira Nogueira Lima, Rodrigo Couto Duarte Drummond, Monize Nakamoto Provisor Santos, Renan Valieris, Rafael Andres Rosales Mitrowsky, Vladmir Cordeiro Lima, Diana Noronha Nunes, Emmanuel Dias-Neto, Israel Tojal da Silva. The interplay between patient´s features and mutational processes in tobacco related cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3245.