Abstract
While obesity is widely recognized as a risk factor for cancer, survival among patients with cancer is often higher for obese than for lean individuals. Several hypotheses have been proposed to explain this “obesity paradox,” but no consensus has yet emerged. Here, we propose a novel hypothesis to add to this emerging debate which suggests that lean healthy persons present conditions unfavorable to malignant transformation, due to powerful natural defenses, whereby only rare but aggressive neoplasms can emerge and develop. In contrast, obese persons present more favorable conditions for malignant transformation, because of several weight‐associated factors and less efficient natural defenses, leading to a larger quantity of neoplasms comprising both nonaggressive and aggressive ones to regularly emerge and progress. If our hypothesis is correct, testing would require the consideration of the raw quantity, not the relative frequency, of aggressive cancers in obese patients compared with lean ones. We also discuss the possibility that in obese persons, nonaggressive malignancies may prevent the subsequent progression of aggressive cancers through negative competitive interactions between tumors.
Highlights
We propose that the effects of obesity on oncogenic process dynamics coupled with its negative effect on the efficiency of natural defense mechanisms could wrongly suggest that obesity has a protective effect
Wang et al (2018) demonstrated that obesity often results in increased immune aging, tumor progression, and PD‐1‐mediated T‐cell dys‐ function partially driven by leptin. Because obesity has both proliferative effects on the dynamics of oncogenesis and negative effects on protective mechanisms, it is expected that obese persons should be prone to malignant problems that are both frequent and highly variable in their level of aggression
While the global picture suggests that obesity could on average protect from devel‐ oping aggressive cancers (Lennon et al, 2016), we suggest that this might be just an misinterpretation
Summary
We propose that the effects of obesity on oncogenic process dynamics coupled with its negative effect on the efficiency of natural defense mechanisms could wrongly suggest that obesity has a protective effect. Apart from this possible misinterpreta‐ tion, it remains possible that in obese patients the same processes favor the early emergence of less aggressive tumors that subsequently prevent the development and growth of more aggressive ones.
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