Obesity paradox in cancer: Is bigger really better?

Újvári, Beáta; Jacqueline, Camille M.; Missé, Dorothée; Amar, Valentin; Fitzpatrick, Jay; Jennings, Geordie; Beckmann, Christa; Rome, Sophie; Biro, Peter A.; Gatenby, Robert A.; Brown, Joel S.; Almeida, Luís; Thomas, Fréderic

doi:10.1111/eva.12790

Cited by 10 publications

(6 citation statements)

References 36 publications

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“…Methodological errors such as selection bias, reverse causality, and collider bias are also assumed to be the cause [ 26 , 28 ], although a study designed to minimize the biases found that the paradox is conserved even after correction [ 10 ]. Ujvari et al [ 29 ] suggested that the immune system, which fights indolent types of precancerous colonies before they differentiate into cancer works more favorable in normal-weight people than obese people. Therefore, the proportion—not the absolute number—of aggressive cancers may be lower in cancer patients with obesity than normal weight, leading to a seemingly better survival in the former [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Association of Body Mass Index with Survival in Asian Patients with Colorectal Cancer

Lee

et al. 2022

Cancer Res Treat

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The clinical significance of body mass index (BMI) on long-term outcomes has not been extensively investigated in Asian patients with colorectal cancer (CRC). This study aims to describe the association between BMI and survival, plus providing BMI cut-off value for predicting prognosis in CRC patients. Materials and MethodsA total of 1,182 patients who had undergone surgery for stage I-III CRC from June 2004 to February 2014 were included. BMI was categorized into four groups based on the recommendation for Asian ethnicity. The optimal BMI cut-off value was determined to maximize overall survival (OS) difference. ResultsIn multivariable analysis, underweight BMI was significantly associated with poor OS (hazard ratio [HR] = 2.38, 95% confidence interval [CI] = 1.55-3.71, p<0.001) and obese BMI was associated with better OS (HR = 0.72, 95% CI = 0.53-0.97, p=0.036) compared with the normal BMI. Overweight and obese BMI were associated with better recurrence-free survival (RFS) (HR = 0.64, 95% CI = 0.42-0.99, p=0.046; HR = 0.58, 95% CI = 0.38-0.89, p=0.014, respectively) compared with the normal BMI group. BMI cut-off value was 20.44 kg/m 2 .Adding the BMI cut-off value to cancer staging could increase discriminatory performance in terms of integrated area under the curve and Harrell's concordance index. ConclusionCompared to normal BMI, underweight BMI was associated with poor survival whereas obese BMI was associated with better survival. BMI cut-off value of 20.44 kg/m 2 is a useful discriminator in Asian patients with CRC.

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Section: Discussionmentioning

confidence: 99%

Association of Body Mass Index with Survival in Asian Patients with Colorectal Cancer

Lee

et al. 2022

Cancer Res Treat

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“…The "obesity paradox" is an intriguing concept in linking adiposity and cancer prognosis (Park et al, 2018;Ujvari et al, 2019). Interestingly, there seems to be a link between obesity and the tumor microenvironment, particularly the immune parameters and mechanisms, especially in CD8 T cells (Turbitt et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles Derived From Colorectal Cancer Affects CD8 T Cells: An Analysis Based on Body Mass Index

Abu

Othman

Razak

et al. 2020

Front. Cell Dev. Biol.

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Colorectal cancer (CRC) is one of the most widely diagnosed cancers worldwide. It has been shown that the body-mass index (BMI) of the patients could influence the tumor microenvironment, treatment response, and overall survival rates. Nevertheless, the mechanism on how BMI affects the tumorigenesis process, particularly the tumor microenvironment is still elusive. Herein, we postulate that extracellular vesicles (EVs) from CRC patients and non-CRC volunteers with different BMI could affect immune cells differently, in CD8 T cells particularly. We isolated the EVs from the archived serum of CRC patients with high and low BMI, as well as healthy controls with similar BMI status. The EVs were further characterized via electron microscopy, western blot and dynamic light scattering. Then, functional analysis was performed on CD8 T cells including apoptosis, cell proliferation, gene expression profiling and cytokine release upon co-incubation with the different EVs. Our results suggest that CRC-derived EVs were able to regulate the CD8 T cells. In some assays, low BMI EVs were functionally different than high BMI EVs. This study highlights the possible difference in the regulatory mechanism of cancer patients-derived EVs, especially on CD8 T cells.

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“…In addition to understanding the TME, recent studies have also demonstrated the importance of patient-associated factors that can impact the response to immunotherapy, such as body composition (fat mass, fat-free mass and muscle quality), sex, ethnicity, age, habits (e.g., smoking, alcohol use, physical activity), past illnesses (immune history) and gut microbiota [ 23 , 24 , 369 – 373 ]. Obesity, currently considered a pandemic, is characterized by changes in the physiology of the entire body.…”

Section: Immunotherapy Cancer and Obesitymentioning

confidence: 99%

The ambiguous role of obesity in oncology by promoting cancer but boosting antitumor immunotherapy

Assumpção

Pasquarelli-do-Nascimento

Duarte

et al. 2022

J Biomed Sci

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Obesity is nowadays considered a pandemic which prevalence’s has been steadily increasingly in western countries. It is a dynamic, complex, and multifactorial disease which propitiates the development of several metabolic and cardiovascular diseases, as well as cancer. Excessive adipose tissue has been causally related to cancer progression and is a preventable risk factor for overall and cancer-specific survival, associated with poor prognosis in cancer patients. The onset of obesity features a state of chronic low-grade inflammation and secretion of a diversity of adipocyte-derived molecules (adipokines, cytokines, hormones), responsible for altering the metabolic, inflammatory, and immune landscape. The crosstalk between adipocytes and tumor cells fuels the tumor microenvironment with pro-inflammatory factors, promoting tissue injury, mutagenesis, invasion, and metastasis. Although classically established as a risk factor for cancer and treatment toxicity, recent evidence suggests mild obesity is related to better outcomes, with obese cancer patients showing better responses to treatment when compared to lean cancer patients. This phenomenon is termed obesity paradox and has been reported in different types and stages of cancer. The mechanisms underlying this paradoxical relationship between obesity and cancer are still not fully described but point to systemic alterations in metabolic fitness and modulation of the tumor microenvironment by obesity-associated molecules. Obesity impacts the response to cancer treatments, such as chemotherapy and immunotherapy, and has been reported as having a positive association with immune checkpoint therapy. In this review, we discuss obesity’s association to inflammation and cancer, also highlighting potential physiological and biological mechanisms underlying this association, hoping to clarify the existence and impact of obesity paradox in cancer development and treatment.

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Obesity paradox in cancer: Is bigger really better?

Cited by 10 publications

References 36 publications

Association of Body Mass Index with Survival in Asian Patients with Colorectal Cancer

Association of Body Mass Index with Survival in Asian Patients with Colorectal Cancer

Extracellular Vesicles Derived From Colorectal Cancer Affects CD8 T Cells: An Analysis Based on Body Mass Index

The ambiguous role of obesity in oncology by promoting cancer but boosting antitumor immunotherapy

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