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Barbaresko J, Lang A, Schiemann TB, Schaefer E, Baechle C, Schwingshackl L, Neuenschwander M, Schlesinger S. Dietary factors and cancer outcomes in individuals with type 2 diabetes: A systematic review and meta-analysis of prospective observational studies. J Diabetes Complications 2025; 39:109060. [PMID: 40311412 DOI: 10.1016/j.jdiacomp.2025.109060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Revised: 04/25/2025] [Accepted: 04/26/2025] [Indexed: 05/03/2025]
Abstract
INTRODUCTION Cancer is a major health concern in persons with type 2 diabetes (T2D). Diet plays an important role in progression of diabetes and cancer. We aimed to systematically summarize the evidence on diet and cancer in individuals with T2D. METHODS PubMed and Web of Science were searched until August 2023 and followed up via PubMed alert until December 2024. Prospective studies investigating any dietary factor in association with cancer in individuals with T2D were eligible. RESULTS We identified 68 studies and conducted 20 meta-analyses. A general low-carbohydrate diet was not associated with cancer outcomes, whereas an inverse association was found for vegetable-based low-carbohydrate diet (HR per 5 points [95 % CI]: 0.90 [0.84, 0.97]; n = 2). We found indications of lower cancer incidence for higher adherence to Dietary Approaches to Stop Hypertension diet, (Alternate) Healthy Eating Index, higher intakes of n-3 fatty acids (0.73 [0.55, 0.98]; n = 2) and higher serum vitamin D (0.95 [0.93, 0.97]; n = 2), as well as a positive association for serum manganese concentrations (1.44 [1.11, 1.87]; n = 2), rated with low to very low certainty of evidence. CONCLUSION So far, the certainty of evidence is very limited due to the small numbers of primary studies. There is an indication of a possible association between diet and cancer risk among persons with T2D, but further well-designed prospective cohort studies are warranted.
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Affiliation(s)
- Janett Barbaresko
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Centre for Diabetes Research at Heinrich Heine University Düsseldorf, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany.
| | - Alexander Lang
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Centre for Diabetes Research at Heinrich Heine University Düsseldorf, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany
| | - Tim Benedict Schiemann
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Centre for Diabetes Research at Heinrich Heine University Düsseldorf, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany; Institute of Nutritional and Food Science, University of Bonn, Bonn, Germany
| | - Edyta Schaefer
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Centre for Diabetes Research at Heinrich Heine University Düsseldorf, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany; German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany
| | - Christina Baechle
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Centre for Diabetes Research at Heinrich Heine University Düsseldorf, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany; German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany
| | - Lukas Schwingshackl
- Institute for Evidence in Medicine, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany
| | - Manuela Neuenschwander
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Centre for Diabetes Research at Heinrich Heine University Düsseldorf, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany; German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany
| | - Sabrina Schlesinger
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Centre for Diabetes Research at Heinrich Heine University Düsseldorf, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany; German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany
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Cheraghpour M, Hatami B, Singal AG. Lifestyle and Pharmacologic Approaches to Prevention of Metabolic Dysfunction-associated Steatotic Liver Disease-related Hepatocellular Carcinoma. Clin Gastroenterol Hepatol 2025; 23:685-694.e6. [PMID: 39800201 DOI: 10.1016/j.cgh.2024.09.041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Revised: 09/19/2024] [Accepted: 09/30/2024] [Indexed: 01/15/2025]
Abstract
Hepatocellular carcinoma (HCC) is a major concern for public health. Fatty liver disease, related to alcohol misuse or metabolic syndrome, has become the leading cause of chronic liver disease and HCC. The strong association between type 2 diabetes mellitus and HCC can be partly attributed to the development of metabolic dysfunction-associated steatotic liver disease (MASLD). There is a strong interest in strategies that may mitigate HCC risk and reduce HCC incidence in this growing population of at-risk individuals. In this review, we describe the pathogenesis of HCC in patients with MASLD and discuss potential emerging pharmacological and lifestyle interventions for MASLD-related HCC. HCC risk has been observed to be lower with healthy lifestyle behaviors, such as healthy dietary patterns (eg, high consumption of vegetables, whole grains, fish and poultry, yogurt, and olive oil, and low consumption of red and processed meats and dietary sugar) and increased physical activity. Selecting an appropriate pharmacologic approach for individuals with MASLD may also decrease the occurrence of HCC. Metformin, PPAR activators, sodium-glucose cotransporter 2 inhibitors, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, aspirin, and statins have all shown promise to reduce the risk of HCC, although guidelines do not recommend their use for the sole purpose of chemoprevention at this time, given a dearth of data defining their risk-benefit ratio.
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Affiliation(s)
- Makan Cheraghpour
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Behzad Hatami
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amit G Singal
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
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Holt D, Contu L, Wood A, Chadwick H, Alborelli I, Insilla AC, Crea F, Hawkes CA. Both Maternal High-Fat and Post-Weaning High-Carbohydrate Diets Increase Rates of Spontaneous Hepatocellular Carcinoma in Aged-Mouse Offspring. Nutrients 2024; 16:2805. [PMID: 39203941 PMCID: PMC11357072 DOI: 10.3390/nu16162805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Revised: 08/19/2024] [Accepted: 08/20/2024] [Indexed: 09/03/2024] Open
Abstract
Both maternal obesity and postnatal consumption of obesogenic diets contribute to the development of metabolic dysfunction-associated steatotic liver disease (MASLD) and hepatocellular carcinoma (HCC). However, there is no consensus as to whether diets that are high in fat or carbohydrates/sugars differentially influence the development of HCC. Moreover, the long-term effects of prenatal HF exposure on HCC and whether this is influenced by postnatal diet has not yet been evaluated. C57BL/6 dams were fed either a low-fat, high-carbohydrate control (C) or low-carbohydrate, high-fat (HF) diet. At weaning, male and female offspring were fed the C or HF diet, generating four diet groups: C/C, C/HF, HF/C and HF/HF. Tissues were collected at 16 months of age and livers were assessed for MASLD and HCC. Glucose regulation and pancreatic morphology were also evaluated. Liver tissues were assessed for markers of glycolysis and fatty acid metabolism and validated using a human HCC bioinformatic database. Both C/HF and HF/HF mice developed obesity, hyperinsulinemia and a greater degree of MASLD than C/C and HF/C offspring. However, despite significant liver and pancreas pathology, C/HF mice had the lowest incidence of HCC while tumour burden was highest in HF/C male offspring. The molecular profile of HCC mouse samples suggested an upregulation of the pentose phosphate pathway and a downregulation of fatty acid synthesis and oxidation, which was largely validated in the human dataset. Both pre-weaning HF diet exposure and post-weaning consumption of a high-carbohydrate diet increased the risk of developing spontaneous HCC in aged mice. However, the influence of pre-weaning HF feeding on HCC development appeared to be stronger in the context of post-weaning obesity. As rates of maternal obesity continue to rise, this has implications for the future incidence of HCC and possible dietary manipulation of offspring carbohydrate intake to counteract this risk.
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Affiliation(s)
- Daniel Holt
- Biomedical and Life Sciences, Lancaster University, Lancaster LA4 1YW, UK (A.W.); (H.C.)
| | - Laura Contu
- School of Psychological Sciences, Bristol University, Bristol BS8 1QU, UK;
| | - Alice Wood
- Biomedical and Life Sciences, Lancaster University, Lancaster LA4 1YW, UK (A.W.); (H.C.)
| | - Hannah Chadwick
- Biomedical and Life Sciences, Lancaster University, Lancaster LA4 1YW, UK (A.W.); (H.C.)
| | - Ilaria Alborelli
- Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, 4056 Basel, Switzerland;
| | - Andrea Cacciato Insilla
- Morphological Diagnostic and Biomolecular Characterization Area, Complex Unit of Pathological Anatomy Empoli and Prato, Usl Toscana Centro, 50122 Florence, Italy
| | - Francesco Crea
- Cancer Research Group, Life, Health and Chemical Sciences, The Open University, Milton Keynes MK7 6AA, UK;
| | - Cheryl A. Hawkes
- Biomedical and Life Sciences, Lancaster University, Lancaster LA4 1YW, UK (A.W.); (H.C.)
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Pham YTH, Jin A, Wang R, Behari J, Koh WP, Yuan JM, Luu HN. Low-Carbohydrate Diet Score and Risk of Hepatocellular Carcinoma: Findings from a Prospective Cohort Study. Cancer Prev Res (Phila) 2024; 17:265-274. [PMID: 38530112 PMCID: PMC11150087 DOI: 10.1158/1940-6207.capr-23-0517] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 02/01/2024] [Accepted: 03/22/2024] [Indexed: 03/27/2024]
Abstract
Limited data are reported on the association between low-carbohydrate diet (LCD) score, a comprehensive measure of dietary pattern according to sources of carbohydrate, fat, and protein, and risk of hepatocellular carcinoma (HCC). We evaluated this score with HCC risk in the Singapore Chinese Health Study, a prospective cohort of 63,275 middle-aged and elderly Chinese living in Singapore and recruited during 1993-1998 period. LCD scores were derived from the semi-quantitative food frequency questionnaire at baseline. A nested case-control study involved 197 HCC cases and 465 controls was also constructed among 28,346 participants who provided blood samples. Cox proportional hazard regression method was used to calculate HRs and 95% confidence intervals (CI) for HCC with different levels of LCD scores. Conditional logistic regression was performed for the case-control study analysis. After 17.6 years of follow-up with 819,573 person-years, 561 participants developed primary HCC. Although there was a null association between total LCD score and HCC risk (HRper-SD increment = 1.07; 95% CI, 0.98-1.16; Ptrend = 0.06), there was a positive association between animal-based LCD and the risk of HCC (HRper-SD increment = 1.11; 95% CI, 1.02-1.21; Ptrend = 0.01). Furthermore, this association was present in both HBsAg-negative and HBsAg-positive individuals in the case-control study. In stratified analysis for the entire cohort, this positive association was only present in those who consumed alcoholic beverages monthly or less frequent but not in weekly or daily drinker (Pinteraction = 0.79). In summary, a diet with lower carbohydrate, higher animal fat and protein was significantly associated with higher risk of HCC among Chinese Singaporeans. PREVENTION RELEVANCE In a large cohort study of more than 63,000 Chinese Singaporeans, we found that a diet with lower carbohydrate and higher animal fat and protein was associated with increased risk of HCC, suggesting that dietary modification could be an effective strategy in primary prevention to reduce the HCC burden.
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Affiliation(s)
- Yen Thi-Hai Pham
- University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA, USA
- Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| | - Aizhen Jin
- Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Renwei Wang
- University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA, USA
| | - Jaideep Behari
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
- Pittsburgh Liver Research Center, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Woon-Puay Koh
- Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore
| | - Jian-Min Yuan
- University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA, USA
- Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| | - Hung N. Luu
- University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA, USA
- Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
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Su F, Koeberle A. Regulation and targeting of SREBP-1 in hepatocellular carcinoma. Cancer Metastasis Rev 2024; 43:673-708. [PMID: 38036934 PMCID: PMC11156753 DOI: 10.1007/s10555-023-10156-5] [Citation(s) in RCA: 20] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 11/10/2023] [Indexed: 12/02/2023]
Abstract
Hepatocellular carcinoma (HCC) is an increasing burden on global public health and is associated with enhanced lipogenesis, fatty acid uptake, and lipid metabolic reprogramming. De novo lipogenesis is under the control of the transcription factor sterol regulatory element-binding protein 1 (SREBP-1) and essentially contributes to HCC progression. Here, we summarize the current knowledge on the regulation of SREBP-1 isoforms in HCC based on cellular, animal, and clinical data. Specifically, we (i) address the overarching mechanisms for regulating SREBP-1 transcription, proteolytic processing, nuclear stability, and transactivation and (ii) critically discuss their impact on HCC, taking into account (iii) insights from pharmacological approaches. Emphasis is placed on cross-talk with the phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt)-mechanistic target of rapamycin (mTOR) axis, AMP-activated protein kinase (AMPK), protein kinase A (PKA), and other kinases that directly phosphorylate SREBP-1; transcription factors, such as liver X receptor (LXR), peroxisome proliferator-activated receptors (PPARs), proliferator-activated receptor γ co-activator 1 (PGC-1), signal transducers and activators of transcription (STATs), and Myc; epigenetic mechanisms; post-translational modifications of SREBP-1; and SREBP-1-regulatory metabolites such as oxysterols and polyunsaturated fatty acids. By carefully scrutinizing the role of SREBP-1 in HCC development, progression, metastasis, and therapy resistance, we shed light on the potential of SREBP-1-targeting strategies in HCC prevention and treatment.
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Affiliation(s)
- Fengting Su
- Michael Popp Institute and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, 6020, Innsbruck, Austria
| | - Andreas Koeberle
- Michael Popp Institute and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, 6020, Innsbruck, Austria.
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Liu Z, Huang H, Xie J, Xu Y, Xu C. Circulating fatty acids and risk of hepatocellular carcinoma and chronic liver disease mortality in the UK Biobank. Nat Commun 2024; 15:3707. [PMID: 38697980 PMCID: PMC11065883 DOI: 10.1038/s41467-024-47960-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Accepted: 04/15/2024] [Indexed: 05/05/2024] Open
Abstract
Nuclear magnetic resonance (NMR)-based plasma fatty acids are objective biomarkers of many diseases. Herein, we aim to explore the associations of NMR-based plasma fatty acids with the risk of hepatocellular carcinoma (HCC) and chronic liver disease (CLD) mortality in 252,398 UK Biobank participants. Here we show plasma levels of n-3 poly-unsaturated fatty acids (PUFA) and n-6 PUFA are negatively associated with the risk of incident HCC [HRQ4vsQ1: 0.48 (95% CI: 0.33-0.69) and 0.48 (95% CI: 0.28-0.81), respectively] and CLD mortality [HRQ4vsQ1: 0.21 (95% CI: 0.13-0.33) and 0.15 (95% CI: 0.08-0.30), respectively], whereas plasma levels of saturated fatty acids are positively associated with these outcomes [HRQ4vsQ1: 3.55 (95% CI: 2.25-5.61) for HCC and 6.34 (95% CI: 3.68-10.92) for CLD mortality]. Furthermore, fibrosis stage significantly modifies the associations between PUFA and CLD mortality. This study contributes to the limited prospective evidence on the associations between plasma-specific fatty acids and end-stage liver outcomes.
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Affiliation(s)
- Zhening Liu
- Department of Gastroenterology, Zhejiang Provincial Clinical Research Center for Digestive Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Hangkai Huang
- Department of Gastroenterology, Zhejiang Provincial Clinical Research Center for Digestive Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Jiarong Xie
- Department of Gastroenterology, Zhejiang Provincial Clinical Research Center for Digestive Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
- Department of Gastroenterology, the First Affiliated Hospital of Ningbo University, Ningbo, 315010, China
| | - Yingying Xu
- Department of Geriatrics, the Third People's Hospital of Yuyao, Yuyao, 311101, China
| | - Chengfu Xu
- Department of Gastroenterology, Zhejiang Provincial Clinical Research Center for Digestive Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
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Zhao L, Li M, Li Y, Hao H, Zhao S, Ma A, Cai J. Association between macronutrients intake and liver dysfunction among tuberculosis patients in rural China. Asia Pac J Clin Nutr 2023; 32:444-459. [PMID: 38135480 PMCID: PMC11090397 DOI: 10.6133/apjcn.202312_32(4).0009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 10/30/2023] [Accepted: 07/29/2023] [Indexed: 12/24/2023]
Abstract
BACKGROUND AND OBJECTIVES Macronutrients play a vital role in liver dysfunction and affect tuberculosis treatment and prognosis. However, macronutrients intake was inadequate for most tuberculosis patients. This study aimed to clarify the associations between macronutrients intake or energy percentages and liver dys-function in tuberculosis patients. METHODS AND STUDY DESIGN In this cross-sectional study, 2581 active tu-berculosis patients aged ≥18 years were included from local tuberculosis clinics in Linyi, China. Macronutrients intake and energy percentages were assessed by 24-hour dietary recalls. The concentration of alanine transferase (ALT) or aspartate transaminase (AST) greater than 40 U/L was defined as liver dysfunction. A restricted cubic spline (RCS) was applied to determine the dose-response relationships. RESULTS Liver dysfunction was assessed for 14.6% (377 patients) of tuberculosis patients. Higher protein (Q2-Q4 in model 1 and 2) or fat intake and fat-to-energy percentages and lower carbohydrate-to-energy percentages (Q4 in model 1) were associated with a decreased incidence of liver dysfunction (p-trend < 0.05). Among those who were male, normal BMI, or consumed energy <1636 kcal/d, inverse associations between protein or fat intake and the risks of liver dysfunction in models were suggested (p-trend < 0.05). Moreover, J-shaped curves in RCS were evident in liver dysfunction tuberculosis patients with protein or fat intake (p-nonlinearity < 0.05). Conclu-sions: Significant linear associations between macronutrients intake or energy percentages and liver dysfunction prevalence were found only in male, normal BMI, or less energy intake patients. The shapes of liver dysfunction-morbidity differed significantly by macronutrients intake or energy percentage.
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Affiliation(s)
- Liangjie Zhao
- Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, Qingdao, China
- Institute of Nutrition and Health, School of Public Health, Qingdao University, Qingdao, China
| | - Mingxin Li
- Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, Qingdao, China
- Institute of Nutrition and Health, School of Public Health, Qingdao University, Qingdao, China
| | - Yue Li
- Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, Qingdao, China
- Institute of Nutrition and Health, School of Public Health, Qingdao University, Qingdao, China
| | - Haibo Hao
- Department of Clinical Nutrition, Yantai Yuhuangding Hospital, Yantai, China
| | - Shanliang Zhao
- Department of Respiratory Medicine, Linyi People's Hospital East Branch, Linyi, China
| | - Aiguo Ma
- Institute of Nutrition and Health, School of Public Health, Qingdao University, Qingdao, China
| | - Jing Cai
- Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, Qingdao, China
- Institute of Nutrition and Health, School of Public Health, Qingdao University, Qingdao, China.
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Zheng C, Lu F, Chen B, Yang J, Yu H, Wang D, Xie H, Chen K, Xie Y, Li J, Bo Z, Wang Y, Chen G, Deng T. Gut microbiome as a biomarker for predicting early recurrence of HBV-related hepatocellular carcinoma. Cancer Sci 2023; 114:4717-4731. [PMID: 37778742 PMCID: PMC10728007 DOI: 10.1111/cas.15983] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 08/17/2023] [Accepted: 09/11/2023] [Indexed: 10/03/2023] Open
Abstract
To investigate the potential of the gut microbiome as a biomarker for predicting the early recurrence of HBV-related hepatocellular carcinoma (HCC), we enrolled 124 patients diagnosed with HBV-associated HCC and 82 HBV-related hepatitis, and 86 healthy volunteers in our study, collecting 292 stool samples for 16S rRNA sequencing and 35 tumor tissue samples for targeted metabolomics. We performed an integrated bioinformatics analysis of gut microbiome and tissue metabolome data to explore the gut microbial-liver metabolite axis associated with the early recurrence of HCC. We constructed a predictive model based on the gut microbiota and validated its efficacy in the temporal validation cohort. Dialister, Veillonella, the Eubacterium coprostanoligenes group, and Lactobacillus genera, as well as the Streptococcus pneumoniae and Bifidobacterium faecale species, were associated with an early recurrence of HCC. We also found that 23 metabolites, including acetic acid, glutamate, and arachidonic acid, were associated with the early recurrence of HCC. A comprehensive analysis of the gut microbiome and tissue metabolome revealed that the entry of gut microbe-derived acetic acid into the liver to supply energy for tumor growth and proliferation may be a potential mechanism for the recurrence of HCC mediated by gut microbe. We constructed a nomogram to predict early recurrence by combining differential microbial species and clinical indicators, achieving an AUC of 78.0%. Our study suggested that gut microbes may serve as effective biomarkers for predicting early recurrence of HCC, and the gut microbial-tumor metabolite axis may explain the potential mechanism by which gut microbes promote the early recurrence of HCC.
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Affiliation(s)
- Chongming Zheng
- Department of Hepatobiliary SurgeryThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
- Hepatobiliary Pancreatic Tumor Bioengineering Cross International Joint Laboratory of Zhejiang ProvinceThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
| | - Fei Lu
- Wenzhou Medical UniversityWenzhouChina
| | - Bo Chen
- Department of Hepatobiliary SurgeryThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
- Hepatobiliary Pancreatic Tumor Bioengineering Cross International Joint Laboratory of Zhejiang ProvinceThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
| | - Jinhuan Yang
- Department of Hepatobiliary SurgeryThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
- Hepatobiliary Pancreatic Tumor Bioengineering Cross International Joint Laboratory of Zhejiang ProvinceThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
| | - Haitao Yu
- Department of Hepatobiliary SurgeryThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
- Hepatobiliary Pancreatic Tumor Bioengineering Cross International Joint Laboratory of Zhejiang ProvinceThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
| | - Daojie Wang
- Department of Hepatobiliary SurgeryThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
- Hepatobiliary Pancreatic Tumor Bioengineering Cross International Joint Laboratory of Zhejiang ProvinceThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
| | - Haonan Xie
- Department of Hepatobiliary SurgeryThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
- Hepatobiliary Pancreatic Tumor Bioengineering Cross International Joint Laboratory of Zhejiang ProvinceThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
| | - Kaiwen Chen
- Department of Hepatobiliary SurgeryThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
- Hepatobiliary Pancreatic Tumor Bioengineering Cross International Joint Laboratory of Zhejiang ProvinceThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
| | - Yitong Xie
- Department of Hepatobiliary SurgeryThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
- Hepatobiliary Pancreatic Tumor Bioengineering Cross International Joint Laboratory of Zhejiang ProvinceThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
| | - Jiacheng Li
- Department of Hepatobiliary SurgeryThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
- Hepatobiliary Pancreatic Tumor Bioengineering Cross International Joint Laboratory of Zhejiang ProvinceThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
| | - Zhiyuan Bo
- Department of Hepatobiliary SurgeryThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
- Hepatobiliary Pancreatic Tumor Bioengineering Cross International Joint Laboratory of Zhejiang ProvinceThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
| | - Yi Wang
- Department of Epidemiology and Biostatistics, School of Public Health and ManagementWenzhou Medical UniversityWenzhouChina
| | - Gang Chen
- Department of Hepatobiliary SurgeryThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
- Hepatobiliary Pancreatic Tumor Bioengineering Cross International Joint Laboratory of Zhejiang ProvinceThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
- Key Laboratory of Diagnosis and Treatment of Severe Hepato‐Pancreatic Diseases of Zhejiang ProvinceThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
- The First Affiliated Hospital of Wenzhou Medical UniversityZhejiang‐Germany Interdisciplinary Joint Laboratory of Hepatobiliary‐Pancreatic Tumor and BioengineeringWenzhouChina
| | - Tuo Deng
- Department of Hepatobiliary SurgeryThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
- Hepatobiliary Pancreatic Tumor Bioengineering Cross International Joint Laboratory of Zhejiang ProvinceThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
- The First Affiliated Hospital of Wenzhou Medical UniversityZhejiang‐Germany Interdisciplinary Joint Laboratory of Hepatobiliary‐Pancreatic Tumor and BioengineeringWenzhouChina
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You Y, Yang T, Wei S, Liu Z, Liu C, Shen Z, Yang Y, Feng Y, Yao P, Zhu Q. Survival of Patients with Hepatitis B-Related Hepatocellular Carcinoma with Concomitant Metabolic Associated Fatty Liver Disease. Diabetes Metab Syndr Obes 2023; 16:2283-2293. [PMID: 37551338 PMCID: PMC10404410 DOI: 10.2147/dmso.s416280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Accepted: 07/24/2023] [Indexed: 08/09/2023] Open
Abstract
Purpose Metabolic associated fatty liver disease is a novel concept defined as fatty liver associated with metabolic disorders. We investigated the effect of metabolic associated fatty liver disease on hepatocellular carcinoma patient mortality. Patients and Methods A total of 624 patients with hepatocellular carcinoma between 2012 and 2020 were enrolled in this retrospective study. Hepatic steatosis was diagnosed using computed tomography or magnetic resonance imaging. Metabolic associated fatty liver disease was defined based on the proposed criteria in 2020. Propensity score matching was performed for patients with metabolic associated fatty liver disease and those without the condition. A Cox proportional hazards regression model was used to evaluate the association between metabolic associated fatty liver disease and hepatocellular carcinoma patient outcomes. Results Patients with hepatocellular carcinoma and metabolic associated fatty liver disease tended to achieve better outcomes than did those without metabolic associated fatty liver disease after matching (p<0.001). Metabolic associated fatty liver disease was significantly associated with better prognosis in patients with concurrent hepatitis B infection (p<0.001). Moreover, high levels of hepatitis B viral DNA in serum samples was associated with a significantly increased risk of death in patients without non-metabolic associated fatty liver disease (p=0.045). Additionally, the association between metabolic associated fatty liver disease and survival in hepatitis B virus-related hepatocellular carcinoma was similar in all subgroups based on metabolic traits. Conclusion Metabolic associated fatty liver disease increases the survival rate of patients with hepatocellular carcinoma and hepatitis B virus infection. The potential interaction of steatosis and virus replication should be considered for future research and clinical treatment strategies.
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Affiliation(s)
- Yajing You
- Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, People’s Republic of China
| | - Tao Yang
- Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, 830000, People’s Republic of China
| | - Shuhang Wei
- Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, People’s Republic of China
| | - Zongxin Liu
- Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, People’s Republic of China
| | - Chenxi Liu
- Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, People’s Republic of China
| | - Zijian Shen
- Department of Radiology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
| | - Yinuo Yang
- Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, People’s Republic of China
| | - Yuemin Feng
- Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, People’s Republic of China
| | - Ping Yao
- Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, 830000, People’s Republic of China
| | - Qiang Zhu
- Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, People’s Republic of China
- Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, 830000, People’s Republic of China
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10
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Leineweber CG, Rabehl M, Pietzner A, Rohwer N, Rothe M, Pech M, Sangro B, Sharma R, Verslype C, Basu B, Sengel C, Ricke J, Schebb NH, Weylandt KH, Benckert J. Sorafenib increases cytochrome P450 lipid metabolites in patient with hepatocellular carcinoma. Front Pharmacol 2023; 14:1124214. [PMID: 36937889 PMCID: PMC10020374 DOI: 10.3389/fphar.2023.1124214] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 02/15/2023] [Indexed: 03/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer death, and medical treatment options are limited. The multikinase inhibitor sorafenib was the first approved drug widely used for systemic therapy in advanced HCC. Sorafenib might affect polyunsaturated fatty acids (PUFA)-derived epoxygenated metabolite levels, as it is also a potent inhibitor of the soluble epoxide hydrolase (sEH), which catalyzes the conversion of cytochrome-P450 (CYP)-derived epoxide metabolites derived from PUFA, such as omega-6 arachidonic acid (AA) and omega-3 docosahexaenoic acid (DHA), into their corresponding dihydroxy metabolites. Experimental studies with AA-derived epoxyeicosatrienoic acids (EETs) have shown that they can promote tumor growth and metastasis, while DHA-derived 19,20-epoxydocosapentaenoic acid (19,20-EDP) was shown to have anti-tumor activity in mice. In this study, we found a significant increase in EET levels in 43 HCC patients treated with sorafenib and a trend towards increased levels of DHA-derived 19,20-EDP. We demonstrate that the effect of sorafenib on CYP- metabolites led to an increase of 19,20-EDP and its dihydroxy metabolite, whereas DHA plasma levels decreased under sorafenib treatment. These data indicate that specific supplementation with DHA could be used to increase levels of the epoxy compound 19,20-EDP with potential anti-tumor activity in HCC patients receiving sorafenib therapy.
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Affiliation(s)
- Can G. Leineweber
- Medical Department B, Division of Hepatology, Gastroenterology, Oncology, Hematology, Palliative Care, Endocrinology, and Diabetes, Brandenburg Medical School, University Hospital Ruppin-Brandenburg, Neuruppin, Germany
- Faculty of Health Sciences, Joint Faculty of the Brandenburg University of Technology, Brandenburg Medical School and University of Potsdam, Potsdam, Germany
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Miriam Rabehl
- Medical Department B, Division of Hepatology, Gastroenterology, Oncology, Hematology, Palliative Care, Endocrinology, and Diabetes, Brandenburg Medical School, University Hospital Ruppin-Brandenburg, Neuruppin, Germany
- Faculty of Health Sciences, Joint Faculty of the Brandenburg University of Technology, Brandenburg Medical School and University of Potsdam, Potsdam, Germany
| | - Anne Pietzner
- Medical Department B, Division of Hepatology, Gastroenterology, Oncology, Hematology, Palliative Care, Endocrinology, and Diabetes, Brandenburg Medical School, University Hospital Ruppin-Brandenburg, Neuruppin, Germany
- Faculty of Health Sciences, Joint Faculty of the Brandenburg University of Technology, Brandenburg Medical School and University of Potsdam, Potsdam, Germany
| | - Nadine Rohwer
- Medical Department B, Division of Hepatology, Gastroenterology, Oncology, Hematology, Palliative Care, Endocrinology, and Diabetes, Brandenburg Medical School, University Hospital Ruppin-Brandenburg, Neuruppin, Germany
- Faculty of Health Sciences, Joint Faculty of the Brandenburg University of Technology, Brandenburg Medical School and University of Potsdam, Potsdam, Germany
- Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
| | | | - Maciej Pech
- Department of Radiology and Nuclear Medicine, Otto-von-Guericke University, Magdeburg, Germany
| | - Bruno Sangro
- Liver Unit and HPB Oncology Area, Clinica Universidad de Navarra and CIBEREHD, Pamplona, Spain
| | - Rohini Sharma
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | - Chris Verslype
- Department of Digestive Oncology, University Hospitals Leuven, Leuven, Belgium
| | - Bristi Basu
- Department of Oncology, University of Cambridge, Cambridge, United Kingdom
| | - Christian Sengel
- Radiology Department, Grenoble University Hospital, La Tronche, France
| | - Jens Ricke
- Department of Radiology, University Hospital, Ludwig-Maximilians-University (LMU) Munich, Munich, Germany
| | - Nils Helge Schebb
- Chair of Food Chemistry, Faculty of Mathematics and Natural Science, University of Wuppertal, Wuppertal, Germany
| | - Karsten-H. Weylandt
- Medical Department B, Division of Hepatology, Gastroenterology, Oncology, Hematology, Palliative Care, Endocrinology, and Diabetes, Brandenburg Medical School, University Hospital Ruppin-Brandenburg, Neuruppin, Germany
- Faculty of Health Sciences, Joint Faculty of the Brandenburg University of Technology, Brandenburg Medical School and University of Potsdam, Potsdam, Germany
| | - Julia Benckert
- Department of Hepatology and Gastroenterology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt—Universität zu Berlin, Berlin, Germany
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11
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Cernea S, Onișor D. Screening and interventions to prevent nonalcoholic fatty liver disease/nonalcoholic steatohepatitis-associated hepatocellular carcinoma. World J Gastroenterol 2023; 29:286-309. [PMID: 36687124 PMCID: PMC9846941 DOI: 10.3748/wjg.v29.i2.286] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Revised: 11/06/2022] [Accepted: 12/21/2022] [Indexed: 01/06/2023] Open
Abstract
Liver cancer is the sixth most commonly diagnosed cancer worldwide, with hepatocellular carcinoma (HCC) comprising most cases. Besides hepatitis B and C viral infections, heavy alcohol use, and nonalcoholic steatohepatitis (NASH)-associated advanced fibrosis/cirrhosis, several other risk factors for HCC have been identified (i.e. old age, obesity, insulin resistance, type 2 diabetes). These might in fact partially explain the occurrence of HCC in non-cirrhotic patients without viral infection. HCC surveillance through effective screening programs is still an unmet need for many nonalcoholic fatty liver disease (NAFLD) patients, and identification of pre-cirrhotic individuals who progress to HCC represents a substantial challenge in clinical practice at the moment. Patients with NASH-cirrhosis should undergo systematic HCC surveillance, while this might be considered in patients with advanced fibrosis based on individual risk assessment. In this context, interventions that potentially prevent NAFLD/ NASH-associated HCC are needed. This paper provided an overview of evidence related to lifestyle changes (i.e. weight loss, physical exercise, adherence to healthy dietary patterns, intake of certain dietary components, etc.) and pharmacological interventions that might play a protective role by targeting the underlying causative factors and pathogenetic mechanisms. However, well-designed prospective studies specifically dedicated to NAFLD/NASH patients are still needed to clarify the relationship with HCC risk.
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Affiliation(s)
- Simona Cernea
- Department M3/Internal Medicine I, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, Târgu Mureş 540139, Romania
- Diabetes, Nutrition and Metabolic Diseases Outpatient Unit, Emergency County Clinical Hospital, Târgu Mureş 540136, Romania
| | - Danusia Onișor
- Department ME2/Internal Medicine VII, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureş, Târgu Mureş 540139, Romania
- Gastroenterology Department, Mureș County Clinical Hospital, Târgu Mureș 540072, Romania
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12
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Sun D, Zhang M, Wei M, Wang Z, Qiao W, Liu P, Zhong X, Liang Y, Chen Y, Huang Y, Yu W. Ox-LDL-mediated ILF3 overexpression in gastric cancer progression by activating the PI3K/AKT/mTOR signaling pathway. Aging (Albany NY) 2022; 14:3887-3909. [PMID: 35507914 PMCID: PMC9134943 DOI: 10.18632/aging.204051] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Accepted: 04/21/2022] [Indexed: 11/25/2022]
Abstract
Background: This study aimed to investigate the relationship of dyslipidemia and interleukin-enhancer binding factor 3 (ILF3) in gastric cancer, and provide insights into the potential application of statins as an agent to prevent and treat gastric cancer. Methods: The expression levels of ILF3 in gastric cancer were examined with publicly available datasets such as TCGA, and western blotting and immunohistochemistry were performed to determine the expression of ILF3 in clinical specimens. The effects of ox-LDL on expression of ILF3 were further verified with western blot analyses. RNA sequencing, Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Gene Set Enrichment Analysis (GSEA) pathway analyses were performed to reveal the potential downstream signaling pathway targets of ILF3. The effects of statins and ILF3 on PI3K/AKT/mTOR signaling pathway, cell proliferation, cell cycle, migration and invasion of gastric cancer cells were investigated with Edu assay, flow cytometry and transwell assay. Results: Immunohistochemistry and western blot demonstrated that the positive expression rates of ILF3 in gastric cancer tissues were higher than adjacent mucosa tissues. The ox-LDL promoted the expression of ILF3 in a time-concentration-dependent manner. ILF3 promoted the proliferation, cell cycle, migration and invasion by activating the PI3K/AKT/mTOR signaling pathway. Statins inhibited the proliferation, cell cycle, migration and invasion of gastric cancer by inhibiting the expression of ILF3. Conclusions: These findings demonstrate that ox-LDL promotes ILF3 overexpression to regulate gastric cancer progression by activating the PI3K/AKT/mTOR signaling pathway. Statins inhibits the expression of ILF3, which might be a new targeted therapy for gastric cancer.
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Affiliation(s)
- Danping Sun
- Department of Gastrointestinal Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Mingxiang Zhang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Meng Wei
- Department of Gastrointestinal Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Zhaoyang Wang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Wen Qiao
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Peng Liu
- Department of Gastrointestinal Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Xin Zhong
- Department of Gastrointestinal Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Yize Liang
- Department of Gastrointestinal Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Yuanyuan Chen
- Department of Nursing Department, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Yadi Huang
- Department of Gastrointestinal Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Wenbin Yu
- Department of Gastrointestinal Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
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13
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Moussa I, Day RS, Li R, Kaseb A, Jalal PK, Daniel‐MacDougall C, Hatia RI, Abdelhakeem A, Rashid A, Chun YS, Li D, Hassan MM. Association of dietary fat intake and hepatocellular carcinoma among US adults. Cancer Med 2021; 10:7308-7319. [PMID: 34535983 PMCID: PMC8525131 DOI: 10.1002/cam4.4256] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 08/05/2021] [Accepted: 08/22/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND AND AIMS The role of dietary fat consumption in the etiology of hepatocellular carcinoma (HCC) remains unclear. We investigated the associations of total fat and fatty acids with risk of HCC among US adults in a hospital-based case-control study. METHODS We analyzed data from 641 cases and 1034 controls recruited at MD Anderson Cancer Center during 2001-2018. Cases were new patients with a pathologically or radiologically confirmed diagnosis of HCC; controls were cancer-free spouses of patients with cancers other than gastrointestinal, lung, liver, or head and neck. Cases and controls were frequency-matched by age and sex. Dietary intake was assessed using a validated food frequency questionnaire. Odds ratios (ORs) and corresponding confidence intervals (CIs) were computed using unconditional logistic regression with adjustment for major HCC risk factors, including hepatitis B virus and hepatitis C virus infection. RESULTS Monounsaturated fatty acid (MUFA) intake was inversely associated with HCC risk (highest vs. lowest tertile: OR, 0.49; 95% CI, 0.33-0.72). Total polyunsaturated fatty acid (PUFA) intake was directly associated with HCC risk (highest vs. lowest tertile: OR, 1.82; 95% CI, 1.23-2.70). Omega-6 PUFA was directly associated with HCC risk (highest vs. lowest tertile: OR 2.29; 95% CI, 1.52-3.44). Long-chain omega-3 PUFA (eicosapentaenoic acid and docosahexaenoic acid) intake was also inversely associated with HCC risk (highest vs. lowest tertile: OR, 0.50; 95% CI, 0.33-0.70). No association was observed for saturated fat and HCC risk. CONCLUSION Our findings support a direct association of omega-6 PUFA intake with HCC and an inverse association of MUFA and long-chain omega-3 PUFA intake with HCC.
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Affiliation(s)
- Iman Moussa
- Department of Epidemiology, Human Genetics, and Environmental ScienceSchool of Public HealthThe University of Texas Health Science Center at HoustonHoustonTexasUSA
| | - Rena S. Day
- Division of Epidemiology, Human Genetics, & Environmental SciencesSouthwest Center for Occupational and Environmental HealthMichael & Susan Dell Center for Healthy LivingSchool of Public HealthThe University of Texas Health Science Center at HoustonHoustonTexasUSA
| | - Ruosha Li
- Department of Biostatistics and Data ScienceSchool of Public HealthThe University of Texas Health Science Center at HoustonHoustonTexasUSA
| | - Ahmed Kaseb
- Department of Gastrointestinal Medical OncologyThe University of Texas MD Anderson Cancer CenterHoustonTexasUSA
| | - Prasun K. Jalal
- Division of Gastroenterology and HepatologyDepartment of MedicineBaylor College of MedicineHoustonTexasUSA
| | | | - Rikita I. Hatia
- Department of EpidemiologyThe University of Texas MD Anderson Cancer CenterHoustonTexasUSA
| | - Ahmed Abdelhakeem
- Department of Internal MedicineBaptist Hospitals of Southeast TexasBeaumontTexasUSA
| | - Asif Rashid
- Department of PathologyThe University of Texas MD Anderson Cancer CenterHoustonTexasUSA
| | - Yun Shin Chun
- Division of SurgeryDepartment of Surgical OncologyThe University of Texas MD Anderson Cancer CenterHoustonTexasUSA
| | - Donghui Li
- Department of Gastrointestinal Medical OncologyThe University of Texas MD Anderson Cancer CenterHoustonTexasUSA
| | - Manal M. Hassan
- Department of EpidemiologyThe University of Texas MD Anderson Cancer CenterHoustonTexasUSA
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14
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Ji X, Wang J, Li Z, Shen Q, Tuo J, Bi J, Tan Y, Li H, Xiang Y. Dietary fat intake and liver cancer risk: A prospective cohort study in Chinese women. Cancer Biol Med 2021; 19:j.issn.2095-3941.2020.0633. [PMID: 34546668 PMCID: PMC8958890 DOI: 10.20892/j.issn.2095-3941.2020.0633] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 04/25/2021] [Indexed: 11/23/2022] Open
Abstract
OBJECTIVE This study aimed to determine whether dietary fat intake increased liver cancer risk in Chinese women from a prospective population-based cohort. METHODS A total of 72,704 Chinese women were followed up from the time of baseline recruitment (1996-2000) to the end of 2016. Dietary fat intake was calculated using a validated food frequency questionnaire. The Cox regression model was used to assess the hazard ratio (HR) and 95% confidence intervals (CI) for dietary fat intake and liver cancer risk. RESULTS We identified 252 incident liver cancer cases out of 1,267,845 person-years during the overall follow-up time. Null associations, neither in quartiles nor per standard deviation (SD) increment, were detected between liver cancer risk and dietary total fat, fat subtypes and subtype ratios, and food sources. The HR (95% CI) of the 1-SD increment was 1.03 (0.90-1.17) for total fat, 1.06 (0.93-1.20) for saturated fat, 1.06 (0.93-1.21) for monounsaturated fat, and 1.00 (0.89-1.13) for polyunsaturated fat. Similar null associations were observed in stratification analyses according to body mass index and menopausal status. CONCLUSIONS In our prospective cohort study, no significant association was observed in Chinese women between dietary fat and liver cancer risk, and in stratification and sensitivity analyses.
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Affiliation(s)
- Xiaowei Ji
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Jing Wang
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Zhuoying Li
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Qiuming Shen
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Jiayi Tuo
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Jinghao Bi
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Yuting Tan
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Honglan Li
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Yongbing Xiang
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
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15
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Luu HN, Neelakantan N, Geng TT, Wang R, Boon-Bee Goh G, Clemente JC, Jin A, van Dam RM, Jia W, Behari J, Koh WP, Yuan JM. Quality diet indexes and risk of hepatocellular carcinoma: Findings from the Singapore Chinese Health Study. Int J Cancer 2021; 148:2102-2114. [PMID: 33129230 PMCID: PMC11572543 DOI: 10.1002/ijc.33367] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Revised: 09/15/2020] [Accepted: 10/19/2020] [Indexed: 02/06/2023]
Abstract
There is limited research on the effect of dietary quality on hepatocellular carcinoma (HCC) risk in populations with relatively high risk of HCC. Using data from Singapore Chinese Health Study, a prospective cohort study, of 63 257 Chinese aged 45 to 74, we assessed four diet-quality index (DQI) scores: the Alternative Health Eating Index-2010 (AHEI-2010), Alternate Mediterranean Diet (aMED), Dietary Approaches to Stop Hypertension (DASH) and Heathy Diet Indicator (HDI). We identified 561 incident HCC cases among the cohort participants after a mean of 17.6 years of follow-up. Cox proportional hazard regression model was used to estimate hazard ratio (HR) and 95% confidence interval (CI) for HCC in relation to these DQI scores. Unconditional logistic regression method was used to evaluate the associations between DQIs and HCC risk among a subset of individuals who tested negative for hepatitis B surface antigen (HBsAg). High scores of AHEI-2010, aMED and DASH, representing higher dietary quality, were associated with lower risk of HCC (all Ptrend < .05). Compared with the lowest quartile, HRs (95% CIs) of HCC for the highest quartile of AHEI-2010, aMED and DASH were 0.69 (0.53-0.89), 0.70 (0.52-0.95) and 0.67 (0.51-0.87), respectively. No significant association between HDI and HCC risk was observed. Among HBsAg-negative individuals, similar inverse associations were observed, and the strongest inverse association was for aMED (HRQ4vsQ1 = 0.46, 95% CI: 0.23-0.94, Ptrend = .10). These findings support the notion that adherence to a healthier diet may lower the risk of HCC, suggesting that dietary modification may be an effective approach for primary prevention of HCC.
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Affiliation(s)
- Hung N. Luu
- Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, UPMC Cancer Pavilion, Pittsburgh, Pennsylvania
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Nithya Neelakantan
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
| | - Ting-ting Geng
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
| | - Renwei Wang
- Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, UPMC Cancer Pavilion, Pittsburgh, Pennsylvania
| | - George Boon-Bee Goh
- Health Services and Systems Research, Duke-NUS Medical School, Singapore, Singapore
- Department of Gastroenterology & Hepatology, Singapore General Hospital, Singapore, Singapore
| | - Jose C. Clemente
- Icahn Institute for Genomics & Multiscale Biology, Department of Genetics and Genomic Sciences, and Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Aizhen Jin
- Health Services and Systems Research, Duke-NUS Medical School, Singapore, Singapore
| | - Rob M van Dam
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore
- Department of Nutrition, Harvard TH Chan School of Public Health, Boston, Massachusetts
| | - Wei Jia
- University of Hawaii Cancer Center, Honolulu, Hawaii
| | - Jaideep Behari
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
- Pittsburgh Liver Research Center, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Woon-Puay Koh
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
- Health Services and Systems Research, Duke-NUS Medical School, Singapore, Singapore
| | - Jian-Min Yuan
- Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, UPMC Cancer Pavilion, Pittsburgh, Pennsylvania
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
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16
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Dietary Fats, Serum Cholesterol and Liver Cancer Risk: A Systematic Review and Meta-Analysis of Prospective Studies. Cancers (Basel) 2021; 13:cancers13071580. [PMID: 33808094 PMCID: PMC8037522 DOI: 10.3390/cancers13071580] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 03/17/2021] [Accepted: 03/23/2021] [Indexed: 12/24/2022] Open
Abstract
Simple Summary Due to the rapid increase of primary liver cancer incidence and the poor prognosis, it is imperative to identify new modifiable factors such as diet and nutrition for the prevention of liver cancer. Diet high in saturated fatty acids (SFA) has been hypothesized to be associated with increased risk of cancers. However, the associations between dietary fatty acids and liver cancer are not consistent. We aimed to examine the association between dietary total fat, its major components, serum cholesterol, and risk of liver cancer combining current evidence from prospective studies. Our meta-analyses provided new evidence on associations between dietary fats, serum cholesterol, and liver cancer risk. Higher intake of dietary SFA was associated with higher risk of liver cancer while higher serum levels of cholesterol and high-density lipoprotein (HDL) were associated with a lower risk of liver cancer with high between-studies variability. Based on our findings, reducing dietary SFA may help to prevent the development of liver cancer. Abstract To quantify the associations between dietary fats and their major components, as well as serum levels of cholesterol, and liver cancer risk, we performed a systematic review and meta-analysis of prospective studies. We searched PubMed, Embase, and Web of Science up to October 2020 for prospective studies that reported the risk estimates of dietary fats and serum cholesterol for liver cancer risk. We carried out highest versus lowest intake or level and dose-response analyses. Higher intake of dietary saturated fatty acids (SFA) was associated with a higher liver cancer risk in both category analysis (relative risk [RR]highest vs. lowest intake = 1.34, 95% confidence interval [CI]: 1.06, 1.69) and dose-response analysis (RR1% energy = 1.04, 95%CI: 1.01, 1.07). Higher serum total cholesterol was inversely associated with liver cancer but with large between-studies variability (RR1 mmol/L = 0.72, 95%CI: 0.69, 0.75, I2 = 75.3%). The inverse association was more pronounced for serum high-density lipoprotein (HDL) cholesterol (RR1 mmol/L = 0.42, 95%CI: 0.27, 0.64). Higher intake of dietary SFA was associated with higher risk of liver cancer while higher serum levels of cholesterol and HDL were associated with a lower risk of liver cancer with high between-studies variability.
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Ji XW, Wang J, Shen QM, Li ZY, Jiang YF, Liu DK, Tan YT, Li HL, Xiang YB. Dietary fat intake and liver cancer incidence: A population-based cohort study in Chinese men. Int J Cancer 2021; 148:2982-2996. [PMID: 33559177 DOI: 10.1002/ijc.33507] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 01/31/2021] [Accepted: 02/02/2021] [Indexed: 02/06/2023]
Abstract
To date, limited studies have focused on the association between dietary fat and liver cancer risk, especially in China. Our study aims to evaluate the association between dietary fat intake and liver cancer incidence risk in men. Dietary fat intake was obtained through a validated food frequency questionnaire in a Chinese prospective cohort. The Cox regression model was utilized to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). After exclusion, 59 998 recruitments were finally analyzed with a total follow-up time of 714 339 person-years, 431 incident liver cancer cases were newly identified among them. The adjusted HRs (95% CIs) for the highest vs lowest quartile of total fat, saturated fat, monounsaturated fat (MUFA), and polyunsaturated fat (PUFA) were 1.33 (1.01-1.75), 1.50 (1.13-1.97), 1.26 (0.96-1.65), and 1.41 (1.07-1.86), and the corresponding P-trend values were .008, .005, .034, and .005, respectively. In the secondary analysis among participants tested for hepatitis B virus, we found that higher intakes of saturated fat and PUFA were also associated with increased liver cancer risks. Besides, high risks of per standard deviation alterations of the total fat, saturated fat and MUFA were detected in liver cancer, and these results were similar to those concluded from the full-cohort analysis. In conclusion, dietary intakes of total fat, saturated fat, PUFA, and probably MUFA might increase liver cancer risks. Our study provides suggestive advice to public administration on dietary suggestions, and related measures taken from managing dietary fat intake might reduce liver cancer incidence.
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Affiliation(s)
- Xiao-Wei Ji
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.,State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Jing Wang
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Qiu-Ming Shen
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.,State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Zhuo-Ying Li
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.,State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Yu-Fei Jiang
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.,State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Da-Ke Liu
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Yu-Ting Tan
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Hong-Lan Li
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Yong-Bing Xiang
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
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Luu HN, Behari J, Goh GBB, Wang R, Jin A, Thomas CE, Clemente JC, Odegaard AO, Koh WP, Yuan JM. Composite Score of Healthy Lifestyle Factors and Risk of Hepatocellular Carcinoma: Findings from a Prospective Cohort Study. Cancer Epidemiol Biomarkers Prev 2021; 30:380-387. [PMID: 33187965 PMCID: PMC7867589 DOI: 10.1158/1055-9965.epi-20-1201] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 09/25/2020] [Accepted: 11/09/2020] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND While the associations between individual lifestyle factors and risk of hepatocellular carcinoma (HCC) have been described previously, their combined impact on HCC risk is unknown. METHODS The association of a composite score of healthy lifestyle factors, including body mass index, alcohol consumption, cigarette smoking, alternative Mediterranean diet, and sleep duration, and HCC risk was examined in the Singapore Chinese Health Study, an ongoing prospective cohort study of 63,257 Chinese men and women. Cox proportional hazard regression method was used to estimate HR and its 95% confidence interval (CI). Conditional logistic regression method was used to evaluate this composite lifestyle score-HCC risk association among a subset of individuals who tested negative for hepatitis B surface antigen (HBsAg) and anti-hepatitis C antibody. RESULTS After a mean follow-up of 17.7 years, 561 participants developed HCC. Individuals with higher composite scores representing healthier lifestyles (range 0-8) were at significantly lower risk of HCC. Compared with the lowest composite score category (0-4), the HRs (95% CIs) for the composite scores of 5, 6, 7, and 8 were 0.67 (0.62-0.85), 0.61 (0.48-0.77), 0.49 (0.37-0.65), and 0.13 (0.06-0.30), respectively (P trend < 0.0001). A similar inverse association was observed in participants with negative HBsAg and anti-hepatitis C virus (HCV)-negative serology (HR, 0.38; 95% CI, 0.19-0.79; for the highest vs. the lowest category of the composite scores; P trend = 0.001). CONCLUSIONS Healthy lifestyles protect against HCC development, especially for individuals without hepatitis B virus and HCV infections. IMPACT This study highlights the importance of a comprehensive lifestyle modification strategy for HCC primary prevention.
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Affiliation(s)
- Hung N Luu
- Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Jaideep Behari
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
- Pittsburgh Liver Research Center, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - George Boon-Bee Goh
- Health Services and Systems Research, Duke-NUS Medical School Singapore, Singapore
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| | - Renwei Wang
- Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Aizhen Jin
- Health Services and Systems Research, Duke-NUS Medical School Singapore, Singapore
| | - Claire E Thomas
- Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Jose C Clemente
- Department of Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, and Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Andrew O Odegaard
- Department of Epidemiology, School of Medicine, University of California-Irvine, Irvine, California
| | - Woon-Puay Koh
- Health Services and Systems Research, Duke-NUS Medical School Singapore, Singapore
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore
| | - Jian-Min Yuan
- Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
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Lust CAC, Bi X, Henry CJ, Ma DWL. Development of Fatty Acid Reference Ranges and Relationship with Lipid Biomarkers in Middle-Aged Healthy Singaporean Men and Women. Nutrients 2021; 13:nu13020435. [PMID: 33572735 PMCID: PMC7911367 DOI: 10.3390/nu13020435] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 01/14/2021] [Accepted: 01/26/2021] [Indexed: 12/17/2022] Open
Abstract
Dietary fatty acids (FA) are essential for overall human health, yet individual FA reference ranges have yet to be established. Developing individual FA reference ranges can provide context to reported concentrations and whether an individual displays deficient, or excess amounts of FA. Reference ranges of sixty-seven individual FA (μmol/L) were profiled and analyzed using gas chromatography with a flame ionization detector from serum samples collected from 476 middle-aged Singaporean males (BMI:23.3 ± 2.9) and females (BMI:21.8 ± 3.6). Measures of triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol (TC) (mmol/L) were also collected. The mean FA concentration seen in this cohort (11,458 ± 2478 was similar to that of overweight North American cohorts assessed in past studies. Ten biologically relevant FA were compared between sexes, with females exhibiting significantly higher concentrations in four FA (p < 0.05). A multiple regression model revealed the ten FA contributed significantly to nearly all lipid biomarkers (p < 0.05). A majority of participants who had FA concentrations in the ≥95th percentile also exhibited TG, HDL, LDL, and TC levels in the “high” risk classification of developing cardiovascular disease. Future studies profiling individual FA reference ranges in many unique, global cohorts are necessary to develop cut-off values of individual FA concentrations highly related to disease-risk.
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Affiliation(s)
- Cody A. C. Lust
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada;
| | - Xinyan Bi
- Clinical Nutrition Research Centre (CNRC), Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), 14 Medical Drive #07-02, MD 6 Building, Singapore 117599, Singapore; (X.B.); (C.J.H.)
| | - Christiani Jeyakumar Henry
- Clinical Nutrition Research Centre (CNRC), Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), 14 Medical Drive #07-02, MD 6 Building, Singapore 117599, Singapore; (X.B.); (C.J.H.)
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore
| | - David W. L. Ma
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada;
- Correspondence:
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George ES, Sood S, Broughton A, Cogan G, Hickey M, Chan WS, Sudan S, Nicoll AJ. The Association between Diet and Hepatocellular Carcinoma: A Systematic Review. Nutrients 2021; 13:nu13010172. [PMID: 33430001 PMCID: PMC7826815 DOI: 10.3390/nu13010172] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Revised: 01/03/2021] [Accepted: 01/05/2021] [Indexed: 12/15/2022] Open
Abstract
Globally, liver cancer is the sixth most common cause of cancer mortality, with hepatocellular carcinoma (HCC) being the most common type of primary liver cancer. Emerging evidence states that diet is recognised as a potential lifestyle-related risk factor for the development of HCC. The aim of this systematic review is to determine whether there is an association between diet and the development of HCC. Using the PRISMA guidelines, three databases (MEDLINE Complete, CINAHL and Embase) were systematically searched, and studies published until July 2020 were included. Thirty observational studies were selected. The protocol was registered with PROSPERO (CRD42019135240). Higher adherence to the Mediterranean dietary pattern, Alternative Healthy Eating Index-2010, the Urban Prudent Dietary Pattern, the Traditional Cantonese Dietary Pattern, intake of vegetables, wholegrains, fish, poultry, coffee, macronutrients such as monounsaturated fats and micronutrients such as vitamin E, vitamin B9, β-carotene, manganese and potassium were associated with a reduced risk of HCC. The results suggest a potential role of diet in the development of HCC. Further quantitative research needs to be undertaken within a range of populations to investigate diet and the relationship with HCC risk.
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Affiliation(s)
- Elena S. George
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong 3217, Australia; (S.S.); (A.B.); (G.C.); (M.H.); (W.S.C.); (S.S.)
- Correspondence: ; Tel.: +61-3-924-68622
| | - Surbhi Sood
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong 3217, Australia; (S.S.); (A.B.); (G.C.); (M.H.); (W.S.C.); (S.S.)
| | - Anna Broughton
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong 3217, Australia; (S.S.); (A.B.); (G.C.); (M.H.); (W.S.C.); (S.S.)
| | - Georgia Cogan
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong 3217, Australia; (S.S.); (A.B.); (G.C.); (M.H.); (W.S.C.); (S.S.)
| | - Megan Hickey
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong 3217, Australia; (S.S.); (A.B.); (G.C.); (M.H.); (W.S.C.); (S.S.)
| | - Wai San Chan
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong 3217, Australia; (S.S.); (A.B.); (G.C.); (M.H.); (W.S.C.); (S.S.)
| | - Sonal Sudan
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong 3217, Australia; (S.S.); (A.B.); (G.C.); (M.H.); (W.S.C.); (S.S.)
| | - Amanda J. Nicoll
- Department of Gastroenterology, Eastern Health, Box Hill 3128, Australia;
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21
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Yang W, Sui J, Ma Y, Simon TG, Petrick JL, Lai M, McGlynn KA, Campbell PT, Giovannucci EL, Chan AT, Zhang X. High Dietary Intake of Vegetable or Polyunsaturated Fats Is Associated With Reduced Risk of Hepatocellular Carcinoma. Clin Gastroenterol Hepatol 2020; 18:2775-2783.e11. [PMID: 31927110 PMCID: PMC7343586 DOI: 10.1016/j.cgh.2020.01.003] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Revised: 12/30/2019] [Accepted: 01/05/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS We investigated associations of intake of total fats, specific dietary fats, and fats from different food sources with risk of hepatocellular carcinoma (HCC) using data from the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). METHODS We analyzed data from a total of 138,483 women and men who participated in the NHS or HPFS. A validated semi-quantitative food frequency questionnaire was sent to NHS participants in 1980, 1984, 1986, and every 4 years thereafter; dietary information was collected from participants in the HPFS in 1986 and every 4 years thereafter. Multivariable hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression. RESULTS After an average follow-up time of 26.6 years, 160 incident HCC cases were documented. Although there was a non-significant association between total fat intake and HCC, intake of vegetable fats reduced risk of HCC (HR for the highest vs lowest quartile, 0.61; 95% CI, 0.39-0.96; Ptrend = .02), but not animal or dairy fats. Replacing animal or dairy fats with an equivalent amount of vegetable fats was associated with a lower risk of HCC (HR per 1 standard deviation, 0.79; 95% CI, 0.65-0.97). Among fat subtypes, monounsaturated and polyunsaturated fatty acids, including n-3 (HR, 0.63; 95% CI, 0.41-0.96; Ptrend = .14) and n-6 polyunsaturated fatty acids (HR, 0.54; 95% CI, 0.34-0.86; Ptrend = .02), were inversely associated with risk of HCC. Higher ratios of monounsaturated or polyunsaturated fat to saturated fat were inversely associated with HCC risk (all Ptrend ≤ .02). In addition, when replacing saturated fats with monounsaturated or polyunsaturated fats, the HR per 1 standard deviation was 0.77 (95% CI, 0.64-0.92). CONCLUSIONS In an analysis of data from 2 large cohort studies, we found higher intake of vegetable fats and polyunsaturated fats to be associated with lower risk of HCC. Replacing animal or dairy fats with vegetable fats, or replacing saturated fats with monounsaturated or polyunsaturated fats, was associated with reduced risk of HCC.
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Affiliation(s)
- Wanshui Yang
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Nutrition, School of Public Health, Anhui Medical University, Hefei, Anhui, PR China
| | - Jing Sui
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu, PR China
| | - Yanan Ma
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; School of Public Health, China Medical University, Shenyang, Liaoning, PR China
| | - Tracey G Simon
- Liver Center, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts
| | - Jessica L Petrick
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland; Slone Epidemiology Center, Boston University, Boston, Massachusetts
| | - Michelle Lai
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Katherine A McGlynn
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Peter T Campbell
- Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia
| | - Edward L Giovannucci
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Andrew T Chan
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts
| | - Xuehong Zhang
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
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N-6 Polyunsaturated Fatty Acids and Risk of Cancer: Accumulating Evidence from Prospective Studies. Nutrients 2020; 12:nu12092523. [PMID: 32825393 PMCID: PMC7551408 DOI: 10.3390/nu12092523] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Revised: 08/14/2020] [Accepted: 08/17/2020] [Indexed: 02/07/2023] Open
Abstract
Previous studies on the association between polyunsaturated fatty acids (PUFAs) and cancer have focused on n-3 PUFAs. To investigate the association between intake or blood levels of n-6 PUFAs and cancer, we searched the PubMed and Embase databases up to March 2020 and conducted a meta-analysis. A total of 70 articles were identified. High blood levels of n-6 PUFAs were associated with an 8% lower risk of all cancers (relative risk (RR) = 0.92; 95% confidence interval (CI): 0.86-0.98) compared to low blood levels of n-6 PUFAs. In the subgroup analyses by cancer site, type of n-6 PUFAs, and sex, the inverse associations were strong for breast cancer (RR = 0.87; 95% CI: 0.77-0.98), linoleic acid (LA) (RR = 0.91; 95% CI: 0.82-1.00), and women (RR = 0.88; 95% CI: 0.79-0.97). In the dose-response analysis, a 2% and 3% decrease in the risk of cancer was observed with a 5% increase in blood levels of n-6 PUFAs and LA, respectively. Thus, there was no significant association between n-6 PUFA intake and the risk of cancer. The pooled RR of cancer for the highest versus lowest category of n-6 PUFA intake was 1.02 (95% CI: 0.99-1.05). Evidence from prospective studies indicated that intake of n-6 PUFAs was not significantly associated with risk of cancer, but blood levels of n-6 PUFAs were inversely associated with risk of cancer.
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Wang J, Zhang Y, Zhao L. Omega-3 PUFA intake and the risk of digestive system cancers: A meta-analysis of observational studies. Medicine (Baltimore) 2020; 99:e20119. [PMID: 32384489 PMCID: PMC7440169 DOI: 10.1097/md.0000000000020119] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND A growing number of epidemiological studies have suggested a possible association between long-chain omega-3 polyunsaturated fatty acid (PUFA) intake and the risk of cancers, but the results have been inconsistent. We aimed to conduct a meta-analysis to assess the association of omega-3 PUFA consumption with digestive system cancers. METHODS Relevant observational studies were identified through a comprehensive search of PubMed, Embase, and the Web of Science through December 2019 and by reviewing the references of the retrieved articles. The relative risks (RRs) of digestive system cancers associated with omega-3 PUFA intake were estimated using a random-effect model and were stratified by region, sex, study design, type of omega-3 PUFAs, smoking status, alcohol consumption, BMI, and physical activity. RESULTS Twenty-five studies (8 case-control studies and 17 cohort studies) involving 1,247,271 participants and 23,173 patients with digestive system cancers were included in this analysis. The risk of digestive system cancers decreased by 17% in individuals who consumed omega-3 PUFAs (RR = 0.83, 95% confidence interval (CI), 0.76-0.91). The risk estimates of digestive system cancers varied by cancer sites, study location, study design, type of omega-3 PUFAs, and other confounders (smoking, alcohol consumption, body mass index, and physical activity). Visual inspection of funnel plots and the Begg's and Egger's tests revealed no evidence of publication bias. CONCLUSION The findings show that omega-3 PUFAs should be as a healthy dietary component for the prevention of digestive system cancers. Cancer incidence decreases with increasing omega-3 PUFAs intake for most digestive system cancer sites. The relation between omega-3 PUFAs and digestive system cancers RR is similar among different populations.
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Abstract
Primary liver cancer is the third leading cause of cancer-related death worldwide. Most patients are diagnosed at late stages with poor prognosis; thus, identification of modifiable risk factors for primary prevention of liver cancer is urgently needed. The well-established risk factors of liver cancer include chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), heavy alcohol consumption, metabolic diseases such as obesity and diabetes, and aflatoxin exposure. However, a large proportion of cancer cases worldwide cannot be explained by current known risk factors. Dietary factors have been suspected as important, but dietary aetiology of liver cancer remains poorly understood. In this review, we summarised and evaluated the observational studies of diet including single nutrients, food and food groups, as well as dietary patterns with the risk of developing liver cancer. Although there are large knowledge gaps between diet and liver cancer risk, current epidemiological evidence supports an important role of diet in liver cancer development. For example, exposure to aflatoxin, heavy alcohol drinking and possibly dairy product (not including yogurt) intake increase, while intake of coffee, fish and tea, light-to-moderate alcohol drinking and several healthy dietary patterns (e.g. Alternative Healthy Eating Index) may decrease liver cancer risk. Future studies with large sample size and accurate diet measurement are warranted and need to consider issues such as the possible aetiological heterogeneity between liver cancer subtypes, the influence of chronic HBV or HCV infection, the high-risk populations (e.g. cirrhosis) and a potential interplay with host gut microbiota or genetic variations.
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Assessment of the Effect of Sorafenib on Omega-6 and Omega-3 Epoxyeicosanoid Formation in Patients with Hepatocellular Carcinoma. Int J Mol Sci 2020; 21:ijms21051875. [PMID: 32182938 PMCID: PMC7084535 DOI: 10.3390/ijms21051875] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Revised: 02/01/2020] [Accepted: 02/08/2020] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer death. The multikinase inhibitor sorafenib is widely used for systemic therapy in advanced HCC. Sorafenib might affect epoxyeicosanoids, as it is also a potent inhibitor of the soluble epoxide hydrolase (sEH), which catalyzes the conversion of epoxides derived from long-chain polyunsaturated fatty acids (PUFAs), such as arachidonic acid (AA) and omega-3 docosahexaenoic acid (DHA), into their corresponding diols. Experimental studies with AA-derived epoxyeicosatrienoic acids (EETs) showed that they can promote tumor growth and metastasis, while DHA-derived 19,20-epoxydocosapentaenoic acid (19,20-EDP) was shown to have anti-tumor activity in mice. In this pilot study, we assessed the effect of sorafenib treatment on the presence of lipid mediators, such as EETs, in blood of the patients with HCC using the lipidomics technology. We found a significant increase in 11,12-EET and 14,15-EET levels in HCC patients treated with sorafenib. Furthermore, while not significant in this small sample set, the data presented indicate that sorafenib can also increase the level of omega-3 DHA-derived 19,20-EDP. While the effect on EETs might hamper the anti-tumor effect of sorafenib, we hypothesize that supplementation of DHA in sorafenib-treated HCC patients could increase the level of 19,20-EDP and thereby enhance its anti-tumor effect.
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Dai L, Huang Y, Ye B, Yang X, An S, Hou M. Natural evolvement of lung tumors induced by N-ethyl-N-nitrosourea (ENU) and the impact of a high sucrose-high fat diet on tumor evolvement assessed by tumor histology in inbred BALB/c and C57BL/6J mice. J Thorac Dis 2019; 11:4735-4745. [PMID: 31903263 DOI: 10.21037/jtd.2019.10.64] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Background The model of lung tumors transplacentally induced by N-ethyl-N-nitrosourea (ENU) in inbred BALB/c and C57BL/6J mice was used to investigate the impact of a high sucrose-high fat (HSHF) diet on lung tumorigenesis. Methods The offspring was separated by gender and randomly divided into 2 subgroups in both ENU- and buffer-treated groups at the time of weaning. One subgroup was put on the standard diet and the other on the HSHF diet from weaning to the age of 24 weeks. The entire lungs went through a standard process of paraffin-embedded blocks. Every lung block was cut in serial sections but one in every five sections was saved to generate step sections that were stained by hematoxylin and eosin. The tumor histology was assessed on the step sections. Results At 24-week checkpoint, a spectrum of histological changes was observed in the mice on both diets. Specifically, they presented as alveolar hyperplasia, adenomas and adenomas with nuclear dysplasia at various degrees. Those tumors were actually at different developmental stages. Lung adenocarcinomas were developed in mice on the HSHF diet. A cluster of tumor cells with wide foamy or clear or signet-ring shaped cytoplasm (fatty changes) appeared in a low frequency on the HSHF diet. Conclusions The observed histological changes indicated that lung tumors were developed at different times and evolved at different paces. The HSHF diet accelerated the course of tumor evolvement. Tumor cells with fatty changes might be induced by the HSHF diet.
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Affiliation(s)
- Lijun Dai
- Laboratory Animal Center of Guangzhou Medical University, Guangzhou 511436, China
| | - Yueling Huang
- Laboratory Animal Center of Guangzhou Medical University, Guangzhou 511436, China
| | - Bingfei Ye
- Laboratory Animal Center of Guangzhou Medical University, Guangzhou 511436, China
| | - Xinbin Yang
- Department of Surgical Thoracic Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Shengli An
- Department of Bio-Statistics, School of Public Health (Guangdong Provincial Key Laboratory of Tropical Disease Research), Southern Medical University, Guangzhou 510515, China
| | - Min Hou
- Department of Pathology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 510095, China
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Bitorina AV, Oligschlaeger Y, Shiri-Sverdlov R, Theys J. Low profile high value target: The role of OxLDL in cancer. Biochim Biophys Acta Mol Cell Biol Lipids 2019; 1864:158518. [PMID: 31479734 DOI: 10.1016/j.bbalip.2019.158518] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Revised: 08/19/2019] [Accepted: 08/26/2019] [Indexed: 12/19/2022]
Abstract
Unhealthy Western-type diet and physical inactivity are highly associated with the current obesity epidemic and its related metabolic diseases such as atherosclerosis and non-alcoholic steatohepatitis. In addition, increasing evidence indicates that obesity is also a major risk factor for several types of common cancers. Recent studies have provided correlative support that disturbed lipid metabolism plays a role in cancer risk and development, pointing towards parallels in metabolic derangements between metabolic diseases and cancer. An important feature of disturbed lipid metabolism is the increase in circulating low-density lipoproteins, which can be oxidized (oxLDL). Elevated oxLDL and the level of its receptors have been positively associated with increased risk of various types of cancer. This review discusses the pro-oncogenic role of oxLDL in tumor development, progression and potential therapies, and provides insights into the underlying mechanisms.
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Affiliation(s)
- Albert V Bitorina
- Department of Molecular Genetics, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
| | - Yvonne Oligschlaeger
- Department of Molecular Genetics, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
| | - Ronit Shiri-Sverdlov
- Department of Molecular Genetics, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands.
| | - Jan Theys
- Department of Precision Medicine, School for Oncology & Developmental Biology (GROW), Maastricht University Medical Centre, Maastricht, the Netherlands.
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28
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Ma Y, Yang W, Simon TG, Smith-Warner SA, Fung TT, Sui J, Chong D, VoPham T, Meyerhardt JA, Wen D, Giovannucci EL, Chan AT, Zhang X. Dietary Patterns and Risk of Hepatocellular Carcinoma Among U.S. Men and Women. Hepatology 2019; 70:577-586. [PMID: 30506561 PMCID: PMC6545168 DOI: 10.1002/hep.30362] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2018] [Accepted: 11/01/2018] [Indexed: 12/16/2022]
Abstract
Although adherence to healthy dietary guidelines has been associated with a reduced risk of several health outcomes, including cardiovascular diseases, type 2 diabetes, and some cancers, little is known about the role of dietary patterns in the development of hepatocellular carcinoma (HCC). We prospectively assessed the associations of three key commonly used a priori dietary patterns-the Alternative Healthy Eating Index-2010 (AHEI-2010), Alternate Mediterranean Diet (AMED), and Dietary Approaches to Stop Hypertension (DASH)-with risk of incident HCC in the Health Professionals Follow-Up Study (HPFS) and the Nurses' Health Study (NHS), two large prospective cohort studies. Diet was assessed almost every 4 years using validated food frequency questionnaires (FFQs). Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression. During up to 32 years of follow-up, 160 incident HCC cases were identified. After adjustment for most HCC risk factors, participants in the highest tertile of Alternative Healthy Eating Index-2010 (AHEI-2010) had a multivariable HR of 0.61 (95% CI, 0.39-0.95; Ptrend = 0.03), compared with those in the lowest tertile. There was a suggestive, but nonsignificant, inverse association for Alternate Mediterranean Diet (AMED; HR = 0.75; 95% CI, 0.49-1.15; Ptrend = 0.18) and a null association for Dietary Approaches to Stop Hypertension (DASH; HR = 0.90; 95% CI, 0.59-1.36; Ptrend = 0.61) in relation to the risk of HCC development. Conclusion: Our findings suggest that better adherence to the AHEI-2010 may decrease the risk of developing HCC among U.S. adults. Future studies are needed to replicate our results, examine these associations in other populations, and elucidate the underlying mechanisms.
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Affiliation(s)
- Yanan Ma
- School of Public Health, China Medical University, Shenyang, Liaoning, P.R. China;,Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Wanshui Yang
- Department of Nutrition, School of Public Health, Anhui Medical University, Hefei, Anhui, P.R. China
| | - Tracey G. Simon
- Liver Center, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA;,Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA;,Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital, Boston, MA, USA
| | - Stephanie A. Smith-Warner
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA;,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Teresa T. Fung
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Jing Sui
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA;,Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of public Health, Southeast University, Nanjing, Jiangsu, P.R. China
| | - Dawn Chong
- National Cancer Centre Singapore, Singapore
| | - Trang VoPham
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA;,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA;,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Jeffrey A. Meyerhardt
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
| | - Deliang Wen
- School of Public Health, China Medical University, Shenyang, Liaoning, P.R. China
| | - Edward L. Giovannucci
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA;,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA;,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Andrew T. Chan
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA;,Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA;,Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital, Boston, MA, USA
| | - Xuehong Zhang
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
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Xue C, He Y, Zhu W, Chen X, Yu Y, Hu Q, Chen J, Liu L, Ren F, Ren Z, Cui G, Sun R. Low expression of LACTB promotes tumor progression and predicts poor prognosis in hepatocellular carcinoma. Am J Transl Res 2018; 10:4152-4162. [PMID: 30662658 PMCID: PMC6325492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2018] [Accepted: 11/04/2018] [Indexed: 06/09/2023]
Abstract
Hepatocellular carcinoma (HCC) is a major life-threatening malignancy worldwide. HCC has an unfavorable prognosis, mainly due to late diagnosis, early metastasis, and post-surgical recurrence. Recent studies have demonstrated that beta-lactamases (LACTB) plays a pivotal role in the pathogenesis and progression of several malignant tumors, but its expression and functional role in HCC has not been reported. In this study, we explored the expression of LACTB using The Cancer Genome Atlas datasets and two independent tissues microarrays. We then analyzed the correlation between LACTB expression and clinical outcomes in HCC. We demonstrated that LACTB mRNA and protein levels were both down-regulated in HCC, and decreased LACTB expression was associated with TNM stage, histologic grade, and overall survival of patients. Additionally, through Gene Set Enrichment Analysis, we found that the genes negatively related to the survival of HCC patients were enriched in the low LACTB expression group. Furthermore, we confirmed that overexpression of LACTB inhibited HCC cell proliferation, invasion, and migration in vitro, as well as decreased tumor growth in vivo. Online prediction results suggested that the LACTB gene was markedly correlated with genes involved in the lipid metabolism pathway. In conclusion, these findings suggest that down-regulated LACTB could function as a novel biomarker for diagnosis and prognosis prediction, and LACTB could serve as a promising target in HCC therapy.
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Affiliation(s)
- Chen Xue
- Precision Medicine Center, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052, China
- Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052, China
| | - Yuting He
- Precision Medicine Center, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052, China
- Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052, China
| | - Weiwei Zhu
- Precision Medicine Center, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052, China
- Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052, China
| | - Xiaolong Chen
- Precision Medicine Center, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052, China
- Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052, China
| | - Yan Yu
- Precision Medicine Center, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052, China
- Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052, China
| | - Qiuyue Hu
- Precision Medicine Center, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052, China
- Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052, China
| | - Jianan Chen
- Precision Medicine Center, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052, China
- Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052, China
| | - Liwen Liu
- Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052, China
| | - Fang Ren
- Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052, China
| | - Zhigang Ren
- Precision Medicine Center, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052, China
- Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052, China
| | - Guangying Cui
- Precision Medicine Center, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052, China
- Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052, China
| | - Ranran Sun
- Precision Medicine Center, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052, China
- Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052, China
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30
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Yang P, Su C, Luo X, Zeng H, Zhao L, Wei L, Zhang X, Varghese Z, Moorhead JF, Chen Y, Ruan XZ. Dietary oleic acid-induced CD36 promotes cervical cancer cell growth and metastasis via up-regulation Src/ERK pathway. Cancer Lett 2018; 438:76-85. [PMID: 30213558 DOI: 10.1016/j.canlet.2018.09.006] [Citation(s) in RCA: 90] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2018] [Revised: 08/03/2018] [Accepted: 09/02/2018] [Indexed: 01/30/2023]
Abstract
Epidemiological and experimental studies have revealed strong associations between dietary lipids and cancer risk. However, the molecular mechanisms underlying the effects of dietary fatty acids on the genesis and progression of cancer have been poorly explored. In this study, we found that a high olive oil diet stimulated cervical cancer (CC) carcinogenesis, and oleic acid (OA), the main lipid in olive oil, was associated with increased malignancy in HeLa cells. OA up-regulated the expression of CD36, which is the best characterized fatty acid transporter. Inhibiting CD36 prevented the tumor-promoting effects of OA, while overexpressing CD36 mimicked the effects of OA. Clinically, CD36 expression was positively correlated with tumor progression and poor prognosis in patients with CC. Furthermore, OA induced Src kinase and downstream ERK1/2 pathway activation in a CD36-dependent manner. Pretreatment of HeLa cells with an Src kinase inhibitor largely blocked the tumor-promoting effect of OA. Our findings suggest that dietary OA exerts a stimulatory effect on CC growth and metastasis, and CD36 might be a promising therapeutic target that acts against CC through an Src/ERK-dependent signaling pathway.
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Affiliation(s)
- Ping Yang
- Centre for Lipid Research & Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, 400016, Chongqing, China
| | - Chunxiao Su
- Centre for Lipid Research & Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, 400016, Chongqing, China
| | - Xuan Luo
- Centre for Lipid Research & Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, 400016, Chongqing, China
| | - Han Zeng
- Centre for Lipid Research & Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, 400016, Chongqing, China
| | - Lei Zhao
- Centre for Lipid Research & Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, 400016, Chongqing, China
| | - Li Wei
- Centre for Lipid Research & Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, 400016, Chongqing, China
| | - Xiaoyu Zhang
- Centre for Lipid Research & Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, 400016, Chongqing, China
| | - Zac Varghese
- John Moorhead Research Laboratory, Centre for Nephrology, University College London Medical School, Royal Free Campus, University College London, London, NW3 2PF, United Kingdom
| | - John F Moorhead
- John Moorhead Research Laboratory, Centre for Nephrology, University College London Medical School, Royal Free Campus, University College London, London, NW3 2PF, United Kingdom
| | - Yaxi Chen
- Centre for Lipid Research & Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, 400016, Chongqing, China.
| | - Xiong Z Ruan
- Centre for Lipid Research & Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, 400016, Chongqing, China; The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (CCID), Zhejiang University, 310058, Hangzhou, China; John Moorhead Research Laboratory, Centre for Nephrology, University College London Medical School, Royal Free Campus, University College London, London, NW3 2PF, United Kingdom.
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31
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Adherence to the Chinese or American Dietary Guidelines is Associated with a Lower Risk of Primary Liver Cancer in China: A Case-Control Study. Nutrients 2018; 10:nu10081113. [PMID: 30126134 PMCID: PMC6115710 DOI: 10.3390/nu10081113] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Revised: 08/09/2018] [Accepted: 08/15/2018] [Indexed: 01/04/2023] Open
Abstract
Adherence to healthy dietary guidelines has been related to a lower risk of several cancers, but its role in primary liver cancer (PLC) has not been fully investigated, especially among Eastern populations. This study enrolled 720 PLC patients and 720 healthy controls who were frequency-matched by age and sex between September 2013 and October 2017 in South China. Dietary quality was assessed by the Chinese Healthy Eating Index (CHEI) and the Healthy Eating Index 2015 (HEI-2015), which manifests as scores of adhering to the 2016 Dietary Guidelines for Chinese and adhering to the 2015–2020 Dietary Guidelines for Americans, respectively. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models, adjusting for potential confounders. Higher scores in both the CHEI and HEI-2015 were associated with a lower risk of PLC (per 5-points increment of the total scores: OR: 0.43, 95% CI: 0.38–0.50 for CHEI; OR: 0.47, 95% CI: 0.40–0.55 for HEI-2015). The protective associations persisted significantly in the stratified analyses by sex, smoker status, alcohol consumption, HBV infection, and histological types of PLC, without statistical evidence for heterogeneity (p-interaction > 0.05). Closer adherence to the most recent dietary guidelines for Chinese or Americans may protect against PLC.
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Sellem L, Srour B, Guéraud F, Pierre F, Kesse-Guyot E, Fiolet T, Lavalette C, Egnell M, Latino-Martel P, Fassier P, Hercberg S, Galan P, Deschasaux M, Touvier M. Saturated, mono- and polyunsaturated fatty acid intake and cancer risk: results from the French prospective cohort NutriNet-Santé. Eur J Nutr 2018; 58:1515-1527. [PMID: 29616321 DOI: 10.1007/s00394-018-1682-5] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2017] [Accepted: 03/28/2018] [Indexed: 12/13/2022]
Abstract
PURPOSE Lipid intakes such as saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids have been widely studied regarding cardiovascular health, but their relevance to cancer is unclear. Inconsistent epidemiological results may be explained by varied mechanisms involving PUFAs and redox balance, inflammatory status and cell signalling, along with interactions with other dietary components such as antioxidants, dietary fibre and more generally fruits and vegetable intakes. Therefore, this study aimed to investigate the associations between lipid intakes and cancer risk, and their potential modulation by vitamin C, vitamin E, dietary fibre and fruit and vegetable intakes. METHODS This prospective study included 44,039 participants aged ≥ 45 years from the NutriNet-Santé cohort (2009-2017). Dietary data were collected using repeated 24 h-dietary records. Multivariable Cox models were performed to characterize associations. RESULTS SFA intake was associated with increased overall [n = 1722 cases, HRQ5vsQ1 = 1.44 (1.10-1.87), p-trend = 0.008] and breast [n = 545 cases, HRQ5vsQ1 = 1.98 (1.24-3.17), p-trend = 0.01] cancer risks. n-6 PUFA [HRQ5vsQ1 = 0.56 (0.32-0.97), p-trend = 0.01] and MUFA (HRQ5vsQ1 = 0.41 [0.18-0.0.95), p-trend = 0.009] intakes were associated with a decreased risk of digestive cancers (n = 190 cases). Associations between n-6 PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intakes and digestive cancer risk were modulated by dietary fibre, vitamin C and fruit and vegetable intakes. CONCLUSION These findings suggested that SFA intake could increase overall and breast cancer risks while some unsaturated fatty acids could decrease digestive cancer risk. However, in line with mechanistic hypotheses, our results suggest that intakes of fruits and vegetables and their constituents (antioxidants, fibre) may interact with PUFAs to modulate these associations.
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Affiliation(s)
- Laury Sellem
- Sorbonne Paris Cité Epidemiology and Statistics Research Center (CRESS), U1153 Inserm, U1125, Inra, Cnam, Paris 13 University, Nutritional Epidemiology Research Team (EREN), Bobigny, France
| | - Bernard Srour
- Sorbonne Paris Cité Epidemiology and Statistics Research Center (CRESS), U1153 Inserm, U1125, Inra, Cnam, Paris 13 University, Nutritional Epidemiology Research Team (EREN), Bobigny, France.
| | - Françoise Guéraud
- INRA UMR1331, TOXALIM (Research Center in Food Toxicology), Université de Toulouse, ENVT, INP, Toulouse, France
| | - Fabrice Pierre
- INRA UMR1331, TOXALIM (Research Center in Food Toxicology), Université de Toulouse, ENVT, INP, Toulouse, France
| | - Emmanuelle Kesse-Guyot
- Sorbonne Paris Cité Epidemiology and Statistics Research Center (CRESS), U1153 Inserm, U1125, Inra, Cnam, Paris 13 University, Nutritional Epidemiology Research Team (EREN), Bobigny, France
| | - Thibault Fiolet
- Sorbonne Paris Cité Epidemiology and Statistics Research Center (CRESS), U1153 Inserm, U1125, Inra, Cnam, Paris 13 University, Nutritional Epidemiology Research Team (EREN), Bobigny, France
| | - Céline Lavalette
- Sorbonne Paris Cité Epidemiology and Statistics Research Center (CRESS), U1153 Inserm, U1125, Inra, Cnam, Paris 13 University, Nutritional Epidemiology Research Team (EREN), Bobigny, France
| | - Manon Egnell
- Sorbonne Paris Cité Epidemiology and Statistics Research Center (CRESS), U1153 Inserm, U1125, Inra, Cnam, Paris 13 University, Nutritional Epidemiology Research Team (EREN), Bobigny, France
| | - Paule Latino-Martel
- Sorbonne Paris Cité Epidemiology and Statistics Research Center (CRESS), U1153 Inserm, U1125, Inra, Cnam, Paris 13 University, Nutritional Epidemiology Research Team (EREN), Bobigny, France
| | - Philippine Fassier
- Sorbonne Paris Cité Epidemiology and Statistics Research Center (CRESS), U1153 Inserm, U1125, Inra, Cnam, Paris 13 University, Nutritional Epidemiology Research Team (EREN), Bobigny, France
| | - Serge Hercberg
- Sorbonne Paris Cité Epidemiology and Statistics Research Center (CRESS), U1153 Inserm, U1125, Inra, Cnam, Paris 13 University, Nutritional Epidemiology Research Team (EREN), Bobigny, France
| | - Pilar Galan
- Sorbonne Paris Cité Epidemiology and Statistics Research Center (CRESS), U1153 Inserm, U1125, Inra, Cnam, Paris 13 University, Nutritional Epidemiology Research Team (EREN), Bobigny, France
| | - Mélanie Deschasaux
- Sorbonne Paris Cité Epidemiology and Statistics Research Center (CRESS), U1153 Inserm, U1125, Inra, Cnam, Paris 13 University, Nutritional Epidemiology Research Team (EREN), Bobigny, France
| | - Mathilde Touvier
- Sorbonne Paris Cité Epidemiology and Statistics Research Center (CRESS), U1153 Inserm, U1125, Inra, Cnam, Paris 13 University, Nutritional Epidemiology Research Team (EREN), Bobigny, France
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Lu Y, Fang J, Zou L, Cui L, Liang X, Lim SG, Dan YY, Ong CN. Omega-6-derived oxylipin changes in serum of patients with hepatitis B virus-related liver diseases. Metabolomics 2018; 14:26. [PMID: 30830341 DOI: 10.1007/s11306-018-1326-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Accepted: 01/18/2018] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Chronic hepatitis B virus (HBV) infection is the main etiologic risk factor for hepatocellular carcinoma (HCC). Early studies indicated that the increase of omega-6-derived oxylipins may be involved in the pathogenesis of HBV-related HCC, yet their changes during the distinct clinical phases of chronic HBV infection remain unclear. To fill this gap, in this study we investigated the omega-6-derived oxylipin profiles in patients with three major clinical stages of chronic HBV infection (chronic hepatitis B, liver cirrhosis, and HCC). METHODS Eighteen omega-6-derived oxylipins were quantified in serum samples of 34 patients with chronic hepatitis B, 46 patients with HBV-related liver cirrhosis, 38 patients with HBV-related HCC, and 50 healthy controls using liquid chromatography tandem mass spectrometry. RESULTS Seven oxylipins were found to be altered in patients with HBV-related liver diseases, including 9,10-dihydroxyoctadecenoic acid (9,10-DiHOME), 12,13-DiHOME, 14,15-dihydroxyeicosatrienoic acid (14,15-DiHETrE), 13-hydroxyoctadecadienoic acid (13-HODE), 12-hydroxyeicosatetraenoic acid (12-HETE), 11-HETE, and thromboxane B2 (TXB2). Of these, three oxylipins derived from the cytochrome P450 (CYP450) pathways including 9,10-DiHOME, 12,13-DiHOME, and 14,15-DiHETrE were found to be associated with the levels of α-fetoprotein (AFP), a tumor marker. In combination with AFP, age, and gender, a combination of these seven differential oxylipins could significantly enhance the prediction of HBV-related liver diseases, particularly for liver cirrhosis (p < 0.05). CONCLUSION This study for the first time shows the correlations between CYP450-derived oxylipins and the progression of chronic HBV infection, and sheds a new light on the surveillance of HBV-related live diseases using oxylipins.
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Affiliation(s)
- Yonghai Lu
- Saw Swee Hock School of Public Health, National University of Singapore, Tahir Foundation Building, Level 11, 12 Science Drive 2, Singapore, 117549, Singapore.
- Institute of Nutrition and Health, Qingdao University, Qingdao, Shandong, China.
| | - Jinling Fang
- Saw Swee Hock School of Public Health, National University of Singapore, Tahir Foundation Building, Level 11, 12 Science Drive 2, Singapore, 117549, Singapore
| | - Li Zou
- Saw Swee Hock School of Public Health, National University of Singapore, Tahir Foundation Building, Level 11, 12 Science Drive 2, Singapore, 117549, Singapore
| | - Liang Cui
- Singapore-MIT Alliance for Research & Technology (SMART), Singapore, Singapore
| | - Xu Liang
- NUS Environment Research Institute, National University of Singapore, Singapore, Singapore
| | - Seng Gee Lim
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, Level 11, 1E Kent Ridge Road, Singapore, 119228, Singapore
| | - Yock-Young Dan
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, Level 11, 1E Kent Ridge Road, Singapore, 119228, Singapore.
| | - Choon Nam Ong
- Saw Swee Hock School of Public Health, National University of Singapore, Tahir Foundation Building, Level 11, 12 Science Drive 2, Singapore, 117549, Singapore
- NUS Environment Research Institute, National University of Singapore, Singapore, Singapore
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Kanda T, Jiang X, Nakamura M, Haga Y, Sasaki R, Wu S, Nakamoto S, Imazeki F, Yokosuka O. Overexpression of the androgen receptor in human hepatoma cells and its effect on fatty acid metabolism. Oncol Lett 2017; 13:4481-4486. [PMID: 28599448 PMCID: PMC5453011 DOI: 10.3892/ol.2017.5973] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2016] [Accepted: 02/03/2017] [Indexed: 12/27/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a predominantly male disease in which the androgen receptor (AR) serves an important pathogenic role in hepatocarcinogenesis. Fatty acid metabolism also contributes to hepatocarcinogenesis and is associated with the prognosis of cancer. The present study aimed to investigate the effects of the AR on fatty acid metabolism-associated gene expression in human hepatoma cell lines. AR-expression plasmids or control plasmids were transiently transfected into the human HCC cell lines Huh7 and HepG2. After 48 h, cellular protein and RNA were extracted and the expression of AR was confirmed by western blotting. Complementary DNA was synthesized and subjected to a quantitative polymerase chain reaction-based array to examine the expression of 84 fatty acid metabolism-associated genes. Overexpression of AR significantly downregulated the expression of 11 fatty acid metabolism-associated genes in Huh7 cells and 35 in HepG2 cells. The overexpression of AR also resulted in the upregulation of 6 fatty acid metabolism genes in HepG2 cells; however, it had no effect in Huh7 cells. Acyl-coenzyme A (CoA) thioesterase 7 and acyl-CoA oxidase 3 were downregulated in both cell lines. In conclusion, upregulation of AR via overexpression led to the disturbance of fatty acid metabolism-associated gene expression in human HCC cells. Therefore, the AR may serve a role in hepatocarcinogenesis via the regulation of hepatocellular fatty acid metabolism.
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Affiliation(s)
- Tatsuo Kanda
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Xia Jiang
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
- Department of General Surgery, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050031, P.R. China
| | - Masato Nakamura
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Yuki Haga
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Reina Sasaki
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Shuang Wu
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Shingo Nakamoto
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
- Department of Molecular Virology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Fumio Imazeki
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
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Krautbauer S, Meier EM, Rein-Fischboeck L, Pohl R, Weiss TS, Sigruener A, Aslanidis C, Liebisch G, Buechler C. Ceramide and polyunsaturated phospholipids are strongly reduced in human hepatocellular carcinoma. Biochim Biophys Acta Mol Cell Biol Lipids 2016; 1861:1767-1774. [PMID: 27570113 DOI: 10.1016/j.bbalip.2016.08.014] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2016] [Revised: 08/16/2016] [Accepted: 08/22/2016] [Indexed: 02/08/2023]
Abstract
Lipid composition affects membrane function, cell proliferation and cell death and is changed in cancer tissues. Hepatocellular carcinoma (HCC) is an aggressive cancer and this study aimed at a comprehensive characterization of hepatic and serum lipids in human HCC. Cholesteryl ester were higher in tumorous tissues (TT) compared to adjacent non-tumorous tissues (NT). Free cholesterol exerting cytotoxic effects was not changed. Phosphatidylethanolamine, -serine (PS) and -inositol but not phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) were reduced in HCC tissues. Saturated species mostly increased and polyunsaturated species were diminished in all of these phospholipids. Ceramide (Cer) was markedly reduced in HCC tissues and higher levels of sphingomyelin suggest impaired sphingomyelinase activity as one of the underlying mechanisms. Importantly, ceramide in NT increased in HCC stage T3. Ceramide released from hepatocytes attracts immune cells and a positive association of the macrophage specific receptor CD163 with NT ceramide was identified. HCC associated lipid changes did not differ in patients suffering from type 2 diabetes. Protein levels of p53 were induced in TT and negatively correlated with Cer d18:1/16:0 and PS 36:1. Of the lipid species changed in HCC tissues only TT Cer d18:1/16:0, Cer d18:1/24:1, PC 38:6 and LPC 22:6 correlated with the respective serum levels. Our study demonstrates a considerably altered hepatic lipidome in HCC tissues. Ceramide was markedly reduced in HCC tissues, and therefore, raising ceramide levels specifically in the tumor represents a reasonable therapeutic approach for the treatment of this malignancy.
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Affiliation(s)
- Sabrina Krautbauer
- Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany; Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany
| | - Elisabeth M Meier
- Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany
| | - Lisa Rein-Fischboeck
- Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany
| | - Rebekka Pohl
- Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany
| | - Thomas S Weiss
- University Children Hospital (KUNO), Regensburg University Hospital, Regensburg, Germany
| | - Alexander Sigruener
- Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany
| | - Charalampos Aslanidis
- Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany
| | - Gerhard Liebisch
- Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany
| | - Christa Buechler
- Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
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36
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NAFLD-Associated Hepatocellular Carcinoma: a Threat to Patients with Metabolic Disorders. ACTA ACUST UNITED AC 2016. [DOI: 10.1007/s11901-016-0297-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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