TITLE: “Exercise and tumor genomic landscapes in 2,702 patients with cancer”
ABSTRACT: Approximately two-thirds of cancer diagnoses globally are attributed to modifiable lifestyle factors such as smoking, diet and inactivity. Conversely, regular exercise is linked to decreased risk of multiple cancers. However, the underlying molecular mechanisms are not fully elucidated. Specifically, how exercise impacts tumor genomic landscapes has not been considered. To address this gap, we integrated clinical annotation of exercise exposure with tumor mutational profiling of 2,702 patients with cancer. Exercise exposure was evaluated by validated questionnaire and tumor genomic profiling of ≥ 505 commonly mutated cancer genes was performed using the Memorial Sloan Kettering Cancer Center Integrated Mutation Profiling of Actional Cancer Targets (MSK-IMPACT) assay. Among the most represented cancer types were breast (n = 629), lung (n = 525), endometrial (n = 260), colorectal (n = 213) and prostate (n = 177). We found that exercise influences the genomic landscapes of tumors in a cancer-type specific manner. For instance, breast and lung cancers from exercising patients had lower tumor mutation burden (TMB) compared with non-exercisers. A pan-cancer analysis revealed a higher risk ratio among exercisers for mutations in ERBB2 and lower risk ratio for mutations in PIK3CA and CDKN2A. Overall, this study shows that exercise regulates tumor genomic landscapes in a cancer-site specific manner.
