Obesity-dependent selection of driver mutations in cancer

Abstract

Obesity is a risk factor for cancer, but whether obesity is linked to specific genomic subtypes of cancer is unknown. We examined the relationship between obesity and tumor genotype in two clinicogenomic corpora. Obesity was associated with specific driver mutations in lung adenocarcinoma, endometrial carcinoma and cancers of unknown primaries, independent of clinical covariates, demographic factors and genetic ancestry. Obesity is therefore a driver of etiological heterogeneity in some cancers. Analysis of pan-cancer clinical genomic sequencing finds that body mass index associates with driver mutations in certain cancer types, including most prominently lung adenocarcinoma. Obesity may thus influence tumor genetics.