Special Issue "Obesity as a Risk Factor for Cancer"

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 October 2018)

Special Issue Editors

Guest Editor
Prof. Dr. Stephan Herzig

Helmholtz Zentrum München, Institute for Diabetes and Cancer IDC, and Joint Heidelberg-IDC Translational Diabetes Program, Heidelberg University Hospital, Ingolstädter Landstraße 1 85764 Neuherberg, Germany
Website | E-Mail
Interests: diabetes complications; energy homeostasis; gene regulation
Guest Editor
Dr. Götz Hartleben

Helmholtz Zentrum München, Institute for Diabetes and Cancer, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany
Website | E-Mail
Interests: cancer cell signaling; -metabolism; -stress response; metabolic vulnerabilities; drug development
Guest Editor
Dr. Mauricio Berriel Diaz

Helmholtz Zentrum München, Institute for Diabetes and Cancer, Ingolstädter Landstraße 1,85764 Neuherberg,Germany
Website | E-Mail
Interests: metabolic dysfunction and cancer; tumor metabolism; cancer-associated wasting (cachexia)

Special Issue Information

Dear Colleagues,

The worldwide increase in obesity constitutes a major medical challenge, with high BMI (body mass index) being an important risk factor for disease. In addition to cardiovascular disorders and development of diabetes, obesity increases the risk for developing cancer. There is convincing evidence, which links obesity with the risk for developing cancers of the esophagus, pancreas, colon, breast, liver, kidney and some hematological malignancies and several mechanisms have been proposed to explain this association. Obesity can result in chronic systemic inflammation, which can drive cancer initiation and influence metastasis. Furthermore, a shift in gut microbiota and thus altered microbial metabolite secretion was suggested to influence tumor development. Obesity is associated with changes in hormone levels with insulin being just one example, which can increase cell growth and survival via increasing intracellular pro-tumorigenic signaling. However, adipokines like leptin and adiponectin were also shown to have an impact on tumor behavior. In recent years, the crosstalk of adipose tissue and immune cells with the tumor has become a focus of investigation. These examples illustrate that systemic metabolism can influence different aspects of tumor development through multiple mechanisms, many of which are not well understood. For instance, there is only limited information on the functional interaction between obesity and the metabolic reprogramming of cancer cells favoring tumor development or how obesity influences tumor maintenance and recurrence.

This Special Issue will highlight the role of obesity as a risk factor for cancer, addressing the molecular mechanisms on the role of obesity in tumor initiation, maintenance and recurrence, cancer intrinsic metabolic alterations and tissue crosstalk with the tumor in obese conditions. The collected reviews will, thereby, shine a light on future therapeutic strategies targeting metabolic cancer etiologies.

Prof. Dr. Stephan Herzig
Dr. Götz Hartleben
Dr. Mauricio Berriel Diaz

Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

  • obesity
  • cancer development
  • metabolic reprogramming
  • tissue-tumor crosstalk

Published Papers (6 papers)

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Research

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Open AccessArticle Metabolic Syndrome and the Risk of Breast Cancer and Subtypes by Race, Menopause and BMI
Cancers 2018, 10(9), 299; https://doi.org/10.3390/cancers10090299
Received: 12 July 2018 / Revised: 24 August 2018 / Accepted: 29 August 2018 / Published: 1 September 2018
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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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Open AccessArticle Visceral Obesity and Metabolic Syndrome Are Associated with Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors
Cancers 2018, 10(9), 293; https://doi.org/10.3390/cancers10090293
Received: 25 July 2018 / Revised: 21 August 2018 / Accepted: 24 August 2018 / Published: 27 August 2018
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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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Open AccessReview Obesity, Leptin and Breast Cancer: Epidemiological Evidence and Proposed Mechanisms
Received: 7 November 2018 / Revised: 20 December 2018 / Accepted: 8 January 2019 / Published: 9 January 2019
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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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Open AccessReview Obesity-Induced TNFα and IL-6 Signaling: The Missing Link between Obesity and Inflammation—Driven Liver and Colorectal Cancers
Received: 16 November 2018 / Revised: 20 December 2018 / Accepted: 21 December 2018 / Published: 27 December 2018
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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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Open AccessReview Obesity-Linked Cancers: Current Knowledge, Challenges and Limitations in Mechanistic Studies and Rodent Models
Cancers 2018, 10(12), 523; https://doi.org/10.3390/cancers10120523
Received: 15 November 2018 / Revised: 9 December 2018 / Accepted: 15 December 2018 / Published: 18 December 2018
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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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Open AccessReview Lipid Metabolic Reprogramming in Hepatocellular Carcinoma
Cancers 2018, 10(11), 447; https://doi.org/10.3390/cancers10110447
Received: 25 October 2018 / Revised: 10 November 2018 / Accepted: 13 November 2018 / Published: 15 November 2018
Cited by 3 | PDF Full-text (1781 KB) | HTML Full-text | XML Full-text
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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