Research

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17 pages, 772 KiB

Open AccessArticle

Influence of Body Mass Index on Long-Term Outcome in Patients with Rectal Cancer—A Single Centre Experience

by Maximilian Kalb, Melanie C. Langheinrich, Susanne Merkel, Christian Krautz, Maximilian Brunner, Alan Bénard, Klaus Weber, Christian Pilarsky, Robert Grützmann and Georg F. Weber

Cancers 2019, 11(5), 609; https://doi.org/10.3390/cancers11050609 - 30 Apr 2019

Cited by 23 | Viewed by 3506

Abstract

Background: Excess bodyweight is known to influence the risk of colorectal cancer; however, little evidence exists for the influence of the body mass index (BMI) on the long-term outcome of patients with rectal cancer. Methods: We assessed the impact of the BMI on [...] Read more.

Background: Excess bodyweight is known to influence the risk of colorectal cancer; however, little evidence exists for the influence of the body mass index (BMI) on the long-term outcome of patients with rectal cancer. Methods: We assessed the impact of the BMI on the risk of local recurrence, distant metastasis and overall—survival in 612 patients between 2003 and 2010 after rectal cancer diagnosis and treatment at the University Hospital Erlangen. A Cox-regression model was used to estimate the hazard ratio and multivariate risk of mortality and distant-metastasis. Median follow up-time was 58 months. Results: Patients with obesity class II or higher (BMI ≥ 35 kg/m², n = 25) and patients with underweight (BMI < 18.5 kg/m², n = 5) had reduced overall survival (hazard ratio (HR) = 1.6; 95% confidence interval (CI) 0.9–2.7) as well as higher rates of distant metastases (hazard ratio HR = 1.7; 95% CI 0.9–3.3) as compared to patients with normal bodyweight (18.5 ≤ BMI < 25 kg/m², n = 209), overweight (25 ≤ BMI <30 kg/m², n = 257) or obesity class I (30 ≤ BMI <35 kg/m², n = 102). There were no significant differences for local recurrence. Conclusions: Underweight and excess bodyweight are associated with lower overall survival and higher rates of distant metastasis in patients with rectal cancer. Full article

(This article belongs to the Special Issue Obesity as a Risk Factor for Cancer)

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13 pages, 605 KiB

Open AccessArticle

Metabolic Syndrome and the Risk of Breast Cancer and Subtypes by Race, Menopause and BMI

by Daniel T. Dibaba, Dejana Braithwaite and Tomi Akinyemiju

Cancers 2018, 10(9), 299; https://doi.org/10.3390/cancers10090299 - 01 Sep 2018

Cited by 31 | Viewed by 4330

Abstract

The objective of this study was to investigate the association of metabolic syndrome (MetS) with the risk of invasive breast cancer and molecular subtypes across race, menopause, and body mass index (BMI) groups. We examined the association of metabolic syndrome and its components [...] Read more.

The objective of this study was to investigate the association of metabolic syndrome (MetS) with the risk of invasive breast cancer and molecular subtypes across race, menopause, and body mass index (BMI) groups. We examined the association of metabolic syndrome and its components with risk of invasive breast cancer among 94,555 female participants of the National Institute of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study, accounting for ductal carcinoma in situ as a competing risk. Cox proportional hazard regression with the Fine and Gray method was used to generate hazard ratios (HR) and 95% confidence intervals (CI) adjusting for baseline sociodemographic, behavioral, and clinical covariates. During a mean follow-up of 14 years, 5380 (5.7%) women developed breast cancer. Overall, MetS at baseline was associated with a 13% increased risk of breast cancer compared to women without MetS (HR: 1.13, 95% CI: 1.00, 1.27); similar estimates were obtained among postmenopausal women (HR: 1.14, 95% CI: 1.01, 1.29). MetS was associated with a slight but non-significantly increased risk of breast cancer among those with both normal weight and overweight/obesity, and those with estrogen receptor positive breast cancer subtype. In the NIH-AARP cohort, MetS was associated with an increased risk of breast cancer. Further studies are needed to definitively evaluate the association of MetS with triple negative breast cancer subtypes across all levels of BMI. Full article

(This article belongs to the Special Issue Obesity as a Risk Factor for Cancer)

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12 pages, 407 KiB

Open AccessArticle

Visceral Obesity and Metabolic Syndrome Are Associated with Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors

by Ana P. Santos, Ana C. Santos, Clara Castro, Luís Raposo, Sofia S. Pereira, Isabel Torres, Rui Henrique, Helena Cardoso and Mariana P. Monteiro

Cancers 2018, 10(9), 293; https://doi.org/10.3390/cancers10090293 - 27 Aug 2018

Cited by 34 | Viewed by 3542

Abstract

The determinants for gastroenteropancreatic neuroendocrine tumors (GEP-NET) recent burden are matters of debate. Obesity and metabolic syndrome (MetS) are well established risks for several cancers even though no link with GEP-NETs was yet established. Our aim in this study was to investigate whether [...] Read more.

The determinants for gastroenteropancreatic neuroendocrine tumors (GEP-NET) recent burden are matters of debate. Obesity and metabolic syndrome (MetS) are well established risks for several cancers even though no link with GEP-NETs was yet established. Our aim in this study was to investigate whether well-differentiated GEP-NETs were associated with obesity and MetS. Patients with well-differentiated GEP-NETs (n = 96) were cross-matched for age, gender, and district of residence with a control group (n = 96) derived from the general population in a case-control study. Patients presented gastro-intestinal (75.0%) or pancreatic (22.9%) tumors, grade G1 (66.7%) or G2 (27.1%) with localized disease (31.3%), regional metastasis (16.7%) or distant metastasis (43.8%) at diagnosis, and 45.8% had clinical hormonal syndromes. MetS was defined according to Joint Interim Statement (JIS) criteria. Well-differentiated GEP-NETs were associated with MetS criteria as well as the individual components’ waist circumference, fasting triglycerides, and fasting plasma glucose (p = 0.003, p = 0.002, p = 0.011 and p < 0.001, respectively). The likelihood of the association was higher when the number of individual MetS components was greater than four. MetS and some individual MetS components including visceral obesity, dyslipidemia, and increased fasting glucose are associated with well-differentiated GEP-NET. This data provides a novel insight in unraveling the mechanisms leading to GEP-NET disease. Full article

(This article belongs to the Special Issue Obesity as a Risk Factor for Cancer)

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Review

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30 pages, 1470 KiB

Open AccessReview

Cell Intrinsic and Systemic Metabolism in Tumor Immunity and Immunotherapy

by Michael F. Coleman, Alyssa J. Cozzo, Alexander J. Pfeil, Suhas K. Etigunta and Stephen D. Hursting

Cancers 2020, 12(4), 852; https://doi.org/10.3390/cancers12040852 - 01 Apr 2020

Cited by 18 | Viewed by 5296

Abstract

Immune checkpoint inhibitor (ICI) therapy has shown extraordinary promise at treating cancers otherwise resistant to treatment. However, for ICI therapy to be effective, it must overcome the metabolic limitations of the tumor microenvironment. Tumor metabolism has long been understood to be highly dysregulated, [...] Read more.

Immune checkpoint inhibitor (ICI) therapy has shown extraordinary promise at treating cancers otherwise resistant to treatment. However, for ICI therapy to be effective, it must overcome the metabolic limitations of the tumor microenvironment. Tumor metabolism has long been understood to be highly dysregulated, with potent immunosuppressive effects. Moreover, T cell activation and longevity within the tumor microenvironment are intimately tied to T cell metabolism and are required for the long-term efficacy of ICI therapy. We discuss in this review the intersection of metabolic competition in the tumor microenvironment, T cell activation and metabolism, the roles of tumor cell metabolism in immune evasion, and the impact of host metabolism in determining immune surveillance and ICI therapy outcomes. We also discussed the effects of obesity and calorie restriction—two important systemic metabolic perturbations that impact intrinsic metabolic pathways in T cells as well as cancer cells. Full article

(This article belongs to the Special Issue Obesity as a Risk Factor for Cancer)

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27 pages, 1397 KiB

Open AccessEditor’s ChoiceReview

Obesity, Leptin and Breast Cancer: Epidemiological Evidence and Proposed Mechanisms

by Sebastiano Andò, Luca Gelsomino, Salvatore Panza, Cinzia Giordano, Daniela Bonofiglio, Ines Barone and Stefania Catalano

Cancers 2019, 11(1), 62; https://doi.org/10.3390/cancers11010062 - 09 Jan 2019

Cited by 144 | Viewed by 13489

Abstract

The prevalence of obesity has been steadily increasing over the past few decades in several developed and developing countries, with resultant hazardous health implications. Substantial epidemiological evidence has shown that excessive adiposity strongly influences risk, prognosis, and progression of various malignancies, including breast [...] Read more.

The prevalence of obesity has been steadily increasing over the past few decades in several developed and developing countries, with resultant hazardous health implications. Substantial epidemiological evidence has shown that excessive adiposity strongly influences risk, prognosis, and progression of various malignancies, including breast cancer. Indeed, it is now well recognized that obesity is a complex physiologic state associated with multiple molecular changes capable of modulating the behavior of breast tumor cells as well of the surrounding microenvironment. Particularly, insulin resistance, hyperactivation of insulin-like growth factor pathways, and increased levels of estrogen due to aromatization by the adipose tissue, inflammatory cytokines, and adipokines contribute to breast cancerogenesis. Among adipokines, leptin, whose circulating levels increase proportionally to total adipose tissue mass, has been identified as a key member of the molecular network in obesity. This review summarizes the current knowledge on the epidemiological link existing between obesity and breast cancer and outlines the molecular mechanisms underlying this connection. The multifaceted role of the obesity adipokine leptin in this respect is also discussed. Full article

(This article belongs to the Special Issue Obesity as a Risk Factor for Cancer)

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21 pages, 1236 KiB

Open AccessEditor’s ChoiceReview

Obesity-Induced TNFα and IL-6 Signaling: The Missing Link between Obesity and Inflammation—Driven Liver and Colorectal Cancers

by Lara Kern, Melanie J. Mittenbühler, Anna Juliane Vesting, Anna Lena Ostermann, Claudia Maria Wunderlich and F. Thomas Wunderlich

Cancers 2019, 11(1), 24; https://doi.org/10.3390/cancers11010024 - 27 Dec 2018

Cited by 176 | Viewed by 12964

Abstract

Obesity promotes the development of numerous cancers, such as liver and colorectal cancers, which is at least partly due to obesity-induced, chronic, low-grade inflammation. In particular, the recruitment and activation of immune cell subsets in the white adipose tissue systemically increase proinflammatory cytokines, [...] Read more.

Obesity promotes the development of numerous cancers, such as liver and colorectal cancers, which is at least partly due to obesity-induced, chronic, low-grade inflammation. In particular, the recruitment and activation of immune cell subsets in the white adipose tissue systemically increase proinflammatory cytokines, such as tumor necrosis factor α (TNFα) and interleukin-6 (IL-6). These proinflammatory cytokines not only impair insulin action in metabolic tissues, but also favor cancer development. Here, we review the current state of knowledge on how obesity affects inflammatory TNFα and IL-6 signaling in hepatocellular carcinoma and colorectal cancers. Full article

(This article belongs to the Special Issue Obesity as a Risk Factor for Cancer)

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20 pages, 959 KiB

Open AccessReview

Obesity-Linked Cancers: Current Knowledge, Challenges and Limitations in Mechanistic Studies and Rodent Models

by Yang Xin Zi Xu and Suresh Mishra

Cancers 2018, 10(12), 523; https://doi.org/10.3390/cancers10120523 - 18 Dec 2018

Cited by 16 | Viewed by 7477

Abstract

The worldwide prevalence of obesity has doubled during the last 50 years, and according to the World Obesity Federation, one third of the people on Earth will be obese by the year 2025. Obesity is described as a chronic, relapsing and multifactorial disease [...] Read more.

The worldwide prevalence of obesity has doubled during the last 50 years, and according to the World Obesity Federation, one third of the people on Earth will be obese by the year 2025. Obesity is described as a chronic, relapsing and multifactorial disease that causes metabolic, biomechanical, and psychosocial health consequences. Growing evidence suggests that obesity is a risk factor for multiple cancer types and rivals smoking as the leading preventable cause for cancer incidence and mortality. The epidemic of obesity will likely generate a new wave of obesity-related cancers with high aggressiveness and shortened latency. Observational studies have shown that from cancer risk to disease prognosis, an individual with obesity is consistently ranked worse compared to their lean counterpart. Mechanistic studies identified similar sets of abnormalities under obesity that may lead to cancer development, including ectopic fat storage, altered adipokine profiles, hormone fluctuations and meta-inflammation, but could not explain how these common mechanisms produce over 13 different cancer types. A major hurdle in the mechanistic underpinning of obesity-related cancer is the lack of suitable pre-clinical models that spontaneously develop obesity-linked cancers like humans. Current approaches and animal models fall short when discerning the confounders that often coexist in obesity. In this mini-review, we will briefly survey advances in the different obesity-linked cancers and discuss the challenges and limitations in the rodent models employed to study their relationship. We will also provide our perspectives on the future of obesity-linked cancer research. Full article

(This article belongs to the Special Issue Obesity as a Risk Factor for Cancer)

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14 pages, 1781 KiB

Open AccessEditor’s ChoiceReview

Lipid Metabolic Reprogramming in Hepatocellular Carcinoma

by Hayato Nakagawa, Yuki Hayata, Satoshi Kawamura, Tomoharu Yamada, Naoto Fujiwara and Kazuhiko Koike

Cancers 2018, 10(11), 447; https://doi.org/10.3390/cancers10110447 - 15 Nov 2018

Cited by 104 | Viewed by 9458

Abstract

Metabolic reprogramming for adaptation to the local environment has been recognized as a hallmark of cancer. Although alterations in fatty acid (FA) metabolism in cancer cells have received less attention compared to other metabolic alterations such as glucose or glutamine metabolism, recent studies [...] Read more.

Metabolic reprogramming for adaptation to the local environment has been recognized as a hallmark of cancer. Although alterations in fatty acid (FA) metabolism in cancer cells have received less attention compared to other metabolic alterations such as glucose or glutamine metabolism, recent studies have uncovered the importance of lipid metabolic reprogramming in carcinogenesis. Obesity and nonalcoholic steatohepatitis (NASH) are well-known risk factors of hepatocellular carcinoma (HCC), and individuals with these conditions exhibit an increased intake of dietary FAs accompanied by enhanced lipolysis of visceral adipose tissue due to insulin resistance, resulting in enormous exogenous FA supplies to hepatocytes via the portal vein and lymph vessels. This “lipid-rich condition” is highly characteristic of obesity- and NASH-driven HCC. Although the way in which HCC cells adapt to such a condition and exploit it to aid their progression is not understood, we recently obtained new insights into this mechanism through lipid metabolic reprogramming. In addition, accumulating evidence supports the importance of lipid metabolic reprogramming in various situations of hepatocarcinogenesis. Thus, in this review, we discuss the latest findings regarding the role of FA metabolism pathways in hepatocarcinogenesis, focusing on obesity- and NASH-driven lipid metabolic reprogramming. Full article

(This article belongs to the Special Issue Obesity as a Risk Factor for Cancer)

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