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Prospective analysis of oncogenic driver mutations and environmental factors: Japan molecular epidemiology for lung cancer study

Kawaguchi, T., Koh, Y., Ando, M., (...), Saka, H., Matsumura, A.

Journal of Clinical Oncology 34, no. 19 (July 2016) 2247-2257

Commentary by Tom Stinchcombe

With the identification of oncogenic drivers of NSCLC there has been increase interest in identifying the potential causative factors, the prevalence and the association of environmental factors and oncogenic events. Many studies are retrospective and the patients tested may not be representative of the lung cancer patient population. This study prospectively collected exposure to active and passive smoke, occupational exposures, reproductive and hormonal risk factors, weight loss, family history of cancer, medication use, and diet and exercise. 72 cancer associated genes, copy number of 5 cancer associated genes, and IHC staining and scoring estrogen receptor and anaplastic lymphoma kinase (ALK) rearrangements were performed. Data on 876 samples (441 ever and 435 never smokers) was analyzed. P53 and KRAS increased proportionally with smoking status, and TP53 and NFE2L2 mutations were observed more frequently in advanced stage. In never smokers no environmental factors were associated with mutational changes. On multivariate analysis KRAS and SMAD4 mutations were associated with high body mass index. Only 3 patients (0.3%) were HPV positive suggesting little contribution of HPV to lung cancer. The prospective collection of prior exposure is a strength of this study, and the limitations are the environmental exposures were patient reported and the use of targeted rather than whole exome or genome sequencing. The study was performed in Japan and the prevalence and associations may vary depending on the patient population studied. Further epidemiological studies are warranted to identify the additional causative agents or environmental exposures associated with NSCLC.

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