The Obesity Paradox in Lung Cancer: Associations With Body Size Versus Body Shape

Ardesch, Frank H.; Ruiter, Rikje; Mulder, Marlies; Lahousse, Lies; Stricker, B. H. C.; Jong, Jessica C. Kiefte‐de

doi:10.3389/fonc.2020.591110

Cited by 32 publications

(29 citation statements)

References 63 publications

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“…This was again revealed in a pooled analysis of 1.6 million patients with 23,732 incident lung cancer cases in which WC was associated with a higher risk of lung cancer. 69 These findings are in agreement with those of Ardesch et al 70 that implicated a positive association between lung cancer risk and an obese body shape (as determined by WC, WHR, and Body Shape Index). Similarly, measurement of visceral adipose tissue was also associated with poor lung cancer prognosis in patients undergoing chemotherapy.…”

Section: Discussionsupporting

confidence: 90%

Visceral Obesity Promotes Lung Cancer Progression—Toward Resolution of the Obesity Paradox in Lung Cancer

Barbi

Patnaik

Pabla³

et al. 2021

Journal of Thoracic Oncology

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Introduction: Although obesity is associated with adverse cancer outcomes in general, most retrospective clinical studies suggest a beneficial effect of obesity in NSCLC.Methods: Hypothesizing that this "obesity paradox" arises partly from the limitations of using body mass index (BMI) to measure obesity, we quantified adiposity using preoperative computed tomography images. This allowed the specific determination of central obesity as abdominal visceral fat area normalized to total fat area (visceral fat index [VFI]). In addition, owing to the previously reported salutary effect of metformin on high-BMI patients with lung cancer, metformin users were excluded. We then explored associations between visceral obesity and outcomes after surgical resection of stage I and II NSCLC. We also explored potential immunologic underpinnings of such association using complimentary analyses of tumor gene expression data from NSCLC tumors and the tumor transcriptome and immune microenvironment in an immunocompetent model of lung cancer with diet-induced obesity.Results: We found that in 513 patients with stage I and II NSCLC undergoing lobectomy, a high VFI is associated with decreased recurrence-free and overall survival. VFI was also inversely related to an inflammatory transcriptomic signature in NSCLC tumors, consistent with observations made in immunocompetent murine models wherein diet-induced obesity promoted cancer progression while exacerbating elements of immune suppression in the tumor niche.Conclusions: In all, this study uses multiple lines of evidence to reveal the adverse effects of visceral obesity in patients with NSCLC, which align with those found in animal models. Thus, the obesity paradox may, at least in part, be secondary to the use of BMI as a measure of obesity and the confounding effects of metformin use.

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Section: Discussionsupporting

confidence: 90%

Visceral Obesity Promotes Lung Cancer Progression—Toward Resolution of the Obesity Paradox in Lung Cancer

Barbi

Patnaik

Pabla³

et al. 2021

Journal of Thoracic Oncology

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“…This different accuracy in detecting cancer risk according to anthropometric assessment is additionally highlighted by evidence about colorectal cancer risk: while the association of BMI is stronger in men than in women, WHR raises the risk in both sexes [118]. Lastly, a recent prospective study concluded that body shape, assessed by WC, WHR, and A Body Shape Index (ABSI), is positively associated with lung cancer risk [125], reverting the aforementioned obesity paradox according to which higher BMI may be protective. Additionally, adult weight variations have been studied as a better metric.…”

Section: Anthropometric Assessment: How To Identify Visceral Obesitymentioning

confidence: 99%

Visceral Adiposity and Cancer: Role in Pathogenesis and Prognosis

2021

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The prevalence of being overweight and obese has been expanded dramatically in recent years worldwide. Obesity usually occurs when the energetic introit overtakes energy expenditure from metabolic and physical activity, leading to fat accumulation mainly in the visceral depots. Excessive fat accumulation represents a risk factor for many chronic diseases, including cancer. Adiposity, chronic low-grade inflammation, and hyperinsulinemia are essential factors of obesity that also play a crucial role in tumor onset. In recent years, several strategies have been pointed toward boundary fat accumulation, thus limiting the burden of cancer attributable to obesity. While remodeling fat via adipocytes browning seems a tempting prospect, lifestyle interventions still represent the main pathway to prevent cancer and enhance the efficacy of treatments. Specifically, the Mediterranean Diet stands out as one of the best dietary approaches to curtail visceral adiposity and, therefore, cancer risk. In this Review, the close relationship between obesity and cancer has been investigated, highlighting the biological mechanisms at the basis of this link. Finally, strategies to remodel fat, including browning and lifestyle interventions, have been taken into consideration as a major perspective to limit excess body weight and tumor onset.

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“…In addition, adipose tissue in overweight cancer patients may represent an energy store that could be used to allow a longer survival time during the disease [ 25 ]. The obesity paradox has been established in many malignancies such as lung cancer [ 156 , 157 , 158 ], renal cell carcinoma [ 159 , 160 , 161 , 162 ], Hodgkin and non-Hodgkin lymphoma (including aggressive B-cell lymphomas) [ 163 , 164 , 165 ], melanoma [ 28 , 166 , 167 ], acute myeloid leukemia [ 168 ], CRC [ 169 , 170 , 171 , 172 , 173 ], or HCC [ 174 ]. In this regard, a meta-analysis of 6,320,365 patients found a negative association between obesity and lung cancer, renal cell carcinoma, and melanoma, suggesting the protective role of obesity [ 175 ].…”

Section: Role Of Leptin As Good Actor In Cancermentioning

confidence: 99%

Leptin, Both Bad and Good Actor in Cancer

Jiménez‐Cortegana¹,

López-Saavedra²,

Sánchez-Jiménez³

et al. 2021

Biomolecules

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Leptin is an important regulator of basal metabolism and food intake, with a pivotal role in obesity. Leptin exerts many different actions on various tissues and systems, including cancer, and is considered as a linkage between metabolism and the immune system. During the last decades, obesity and leptin have been associated with the initiation, proliferation and progression of many types of cancer. Obesity is also linked with complications and mortality, irrespective of the therapy used, affecting clinical outcomes. However, some evidence has suggested its beneficial role, called the “obesity paradox”, and the possible antitumoral role of leptin. Recent data regarding the immunotherapy of cancer have revealed that overweight leads to a more effective response and leptin may probably be involved in this beneficial process. Since leptin is a positive modulator of both the innate and the adaptive immune system, it may contribute to the increased immune response stimulated by immunotherapy in cancer patients and may be proposed as a good actor in cancer. Our purpose is to review this dual role of leptin in cancer, as well as trying to clarify the future perspectives of this adipokine, which further highlights its importance as a cornerstone of the immunometabolism in oncology.

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The Obesity Paradox in Lung Cancer: Associations With Body Size Versus Body Shape

Cited by 32 publications

References 63 publications

Visceral Obesity Promotes Lung Cancer Progression—Toward Resolution of the Obesity Paradox in Lung Cancer

Visceral Obesity Promotes Lung Cancer Progression—Toward Resolution of the Obesity Paradox in Lung Cancer

Visceral Adiposity and Cancer: Role in Pathogenesis and Prognosis

Leptin, Both Bad and Good Actor in Cancer

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