Obesity-related genomic instability and altered xenobiotic metabolism: possible consequences for cancer risk and chemotherapy

Abstract

The increase in the prevalence of obesity has led to an elevated risk for several associated diseases including cancer. Several studies have investigated the DNA damage in human blood samples and showed a clear trend towards increased DNA damage in obesity. Reduced genomic stability is thus one of the consequences of obesity, which may contribute to the related cancer risk. Whether this is influenced by compromised DNA repair has not been elucidated sufficiently yet. On the other hand, obesity has also been linked to reduced therapy survival and increased adverse effects during chemotherapy, although the available data are controversial. Despite some indications that obesity might alter hepatic metabolism, current literature in humans is insufficient, and results from animal studies are inconclusive. Here we have summarised published data on hepatic drug metabolism to understand the impact of obesity on cancer therapy better. Furthermore, we highlight knowledge gaps in the interrelationship between obesity and drug metabolism from a toxicological perspective.

Keywords: Cancer; Chemotherapy; DNA damage repair; Drug metabolism; Obesity.

Fig. 1.

Overview on the relationship between obesity, cancer risk and cancer therapy. ang II: angiotensin II, IR: insulin resistance, T2DM: type 2 diabetes mellitus, NAFLD: non-alcoholic fatty liver disease.