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1
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Nguyen HTM, Gunathilake M, Lee J, Oh JH, Chang HJ, Sohn DK, Shin A, Kim J. A higher dietary alpha-linolenic acid intake is associated with lower colorectal cancer risk based on MUC4 rs2246901 variant among Korean adults. Nutr Res 2024; 131:71-82. [PMID: 39369551 DOI: 10.1016/j.nutres.2024.09.003] [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: 05/31/2024] [Revised: 09/02/2024] [Accepted: 09/03/2024] [Indexed: 10/08/2024]
Abstract
Alpha-linolenic acid (C18:3n-3 [ALA]) intake may have a beneficial effect in reducing cancer risk; however, its association with colorectal cancer (CRC) risk remains conflicted. Additionally, ALA was emphasized as being associated with mucins, an important glycoproteins family within the intestine. Thus, we hypothesized that a higher dietary ALA intake may reduce the risk of CRC and this preventive effect has an interaction with mucin 4 (MUC4) rs2246901. We conducted a case-control study at the National Cancer Center in Korea, involving 1039 cases and 1982 controls, aiming to determine the interaction of the MUC4 rs2246901 polymorphism and ALA intake in CRC risk. Dietary ALA intake was collected via semiquantitative food frequency questionnaire (SQFFQ), categorizing by 4 quartiles. We evaluated the odds ratios (ORs) and 95% confidence intervals (CIs) through unconditional logistic regression models. Higher dietary ALA intake was found to be inversely associated with CRC risk (adjusted OR = 0.58; 95% CI, 0.45-0.75, P for trend < .001). No significant association between MUC4 rs2246901 polymorphism and CRC risk was found. In a recessive model, MUC4 rs2246901 seemed to modify this association; participants with at least 1 major allele and higher ALA intake had a significantly lower CRC risk than those who had a lower intake (adjusted OR = 0.56; 95% CI, 0.43-0.72; P interaction = .047). A higher dietary ALA was proposed as a potential protective nutrient against CRC. Moreover, this association might be influenced by presence of the MUC4 rs2246901 polymorphism.
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Affiliation(s)
- Ha Thi Mien Nguyen
- Department of Cancer Control & Population Health, Graduate School of Cancer Science and Policy, Goyang-si, Gyeonggi-do, Korea
| | - Madhawa Gunathilake
- Department of Cancer AI & Digital Health, Graduate School of Cancer Science and Policy, Goyang-si, Gyeonggi-do, Korea
| | - Jeonghee Lee
- Department of Cancer AI & Digital Health, Graduate School of Cancer Science and Policy, Goyang-si, Gyeonggi-do, Korea
| | - Jae Hwan Oh
- Center for Colorectal Cancer, National Cancer Center Hospital, National Cancer Center, Goyang-si, Gyeonggi-do, South Korea
| | - Hee Jin Chang
- Center for Colorectal Cancer, National Cancer Center Hospital, National Cancer Center, Goyang-si, Gyeonggi-do, South Korea
| | - Dae Kyung Sohn
- Center for Colorectal Cancer, National Cancer Center Hospital, National Cancer Center, Goyang-si, Gyeonggi-do, South Korea
| | - Aesun Shin
- Department of Preventive Medicine, Seoul National University College of Medicine, Jongno-gu, Seoul, South Korea
| | - Jeongseon Kim
- Department of Cancer AI & Digital Health, Graduate School of Cancer Science and Policy, Goyang-si, Gyeonggi-do, Korea.
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2
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Tojjari A, Choucair K, Sadeghipour A, Saeed A, Saeed A. Anti-Inflammatory and Immune Properties of Polyunsaturated Fatty Acids (PUFAs) and Their Impact on Colorectal Cancer (CRC) Prevention and Treatment. Cancers (Basel) 2023; 15:4294. [PMID: 37686570 PMCID: PMC10487099 DOI: 10.3390/cancers15174294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 08/24/2023] [Accepted: 08/25/2023] [Indexed: 09/10/2023] Open
Abstract
Colorectal cancer (CRC) remains a leading cause of death from cancer worldwide, with increasing incidence in the Western world. Diet has become the focus of research as a significant risk factor for CRC occurrence, and the role of dietary polyunsaturated fatty acids (PUFAs) has become an area of interest given their potential role in modulating inflammation, particularly in the pro-carcinogenic inflammatory environment of the colon. This work reviews the main types of PUFAs, their characteristics, structure, and physiologic role. We then highlight their potential role in preventing CRC, their signaling function vis-à-vis tumorigenic signaling, and their subsequent potential role in modulating response to different treatment modalities. We review pre-clinical and clinical data and discuss their potential use as adjunct therapies to currently existing treatment modalities. Given our understanding of PUFAs' immune and inflammation modulatory effects, we explore the possible combination of PUFAs with immune checkpoint inhibitors and other targeted therapies.
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Affiliation(s)
- Alireza Tojjari
- Division of Hematology and Oncology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA;
| | - Khalil Choucair
- Division of Hematology and Oncology, Department of Medicine, Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, USA;
| | - Arezoo Sadeghipour
- Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modarres University, Tehran 14115-175, Iran;
| | - Azhar Saeed
- Department of Pathology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA;
| | - Anwaar Saeed
- Division of Hematology and Oncology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA;
- UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA
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3
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Wang T, Brown NM, McCoy AN, Sandler RS, Keku TO. Omega-3 Polyunsaturated Fatty Acids, Gut Microbiota, Microbial Metabolites, and Risk of Colorectal Adenomas. Cancers (Basel) 2022; 14:4443. [PMID: 36139601 PMCID: PMC9496906 DOI: 10.3390/cancers14184443] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 09/02/2022] [Accepted: 09/08/2022] [Indexed: 11/17/2022] Open
Abstract
Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are thought to protect against colorectal adenoma (CRA) development. We aimed to further understand the underlying mechanisms by examining the relationships between ω-3 PUFAs and the gut microbiota on CRAs. We assessed the mucosal microbiota via bacterial 16S rRNA sequencing among 217 CRA cases and 218 controls who completed PUFA intake questionnaires. The overall microbial composition was assessed by α-diversity measurements (diversity, richness, and evenness). Global metabolomics was conducted using a random subset of case−control pairs (n = 50). We compared microbiota and metabolite signatures between cases and controls according to fold change (FC). Odds ratios (OR) and confidence intervals (CI) were estimated from logistic regression for associations of ω-3 PUFAs and the microbiota with CRAs. We observed an inverse association between overall ω-3 PUFA intake and CRAs, especially for short-chain ω -3 PUFAs (OR = 0.45, 95% CI: 0.21, 0.97). Such inverse associations were modified by bacterial evenness (p-interaction = 0.03). Participants with higher levels (FC > 2) of bile acid-relevant metabolites were more likely to have CRAs than the controls, and the correlation between bile acids and bacterial diversity differed by case−control status. Our findings suggest that ω-3 PUFAs are inversely associated with CRA development, and the association may be modified by gut microbiota profiles.
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Affiliation(s)
- Tengteng Wang
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
| | - Nicole M. Brown
- Center for Gastrointestinal Disease and Biology, University of North Carolina, Chapel Hill, NC 27599, USA
| | - Amber N. McCoy
- Center for Gastrointestinal Disease and Biology, University of North Carolina, Chapel Hill, NC 27599, USA
| | - Robert S. Sandler
- Center for Gastrointestinal Disease and Biology, University of North Carolina, Chapel Hill, NC 27599, USA
- Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Temitope O. Keku
- Center for Gastrointestinal Disease and Biology, University of North Carolina, Chapel Hill, NC 27599, USA
- Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
- Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
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4
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Tu M, Sun Q, Zhang J, Zhang G. Comparative Effects of Traditional Versus Genetically Modified Soybean Oils on Colon Tumorigenesis in Mice. Foods 2022; 11:foods11131937. [PMID: 35804751 PMCID: PMC9265295 DOI: 10.3390/foods11131937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 06/24/2022] [Accepted: 06/25/2022] [Indexed: 11/21/2022] Open
Abstract
Soybean oil, which has high abundance of linoleic acid (LA, 18:2ω-6), is the most commonly consumed edible oil. Recent studies support that a high dietary intake of LA is linked with increased risks of developing colonic inflammation and colon cancer. Here we studied the effects of the genetically modified Plenish® soybean oil, which has low abundance of LA as well as α-linolenic acid (ALA, 18:3ω-3), on development of azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colon tumorigenesis in mice. Compared with a diet rich in traditional soybean oil, administration of a diet enriched with the Plenish oil has little impact on AOM/DSS-induced colon tumorigenesis, colonic infiltration of immune cells, expressions of inflammatory genes, and tumor markers. These results suggest that the traditional and the Plenish soybean oils have similar effects on development of AOM/DSS-induced colon cancer in mice.
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Affiliation(s)
- Maolin Tu
- Department of Food Science, University of Massachusetts, Amherst, MA 01003, USA; (M.T.); (J.Z.)
- School of Food Science and Technology, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian 116034, China
| | - Quancai Sun
- Department of Food Science and Technology, National University of Singapore, Singapore 117542, Singapore;
| | - Jianan Zhang
- Department of Food Science, University of Massachusetts, Amherst, MA 01003, USA; (M.T.); (J.Z.)
| | - Guodong Zhang
- Department of Food Science, University of Massachusetts, Amherst, MA 01003, USA; (M.T.); (J.Z.)
- Department of Food Science and Technology, National University of Singapore, Singapore 117542, Singapore;
- Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, MA 01003, USA
- Correspondence:
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5
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Aldoori J, Cockbain AJ, Toogood GJ, Hull MA. Omega-3 polyunsaturated fatty acids: moving towards precision use for prevention and treatment of colorectal cancer. Gut 2022; 71:822-837. [PMID: 35115314 DOI: 10.1136/gutjnl-2021-326362] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 12/19/2021] [Indexed: 12/12/2022]
Abstract
Data from experimental studies have demonstrated that marine omega-3 polyunsaturated fatty acids (O3FAs) have anti-inflammatory and anticancer properties. In the last decade, large-scale randomised controlled trials of pharmacological delivery of O3FAs and prospective cohort studies of dietary O3FA intake have continued to investigate the relationship between O3FA intake and colorectal cancer (CRC) risk and mortality. Clinical data suggest that O3FAs have differential anti-CRC activity depending on several host factors (including pretreatment blood O3FA level, ethnicity and systemic inflammatory response) and tumour characteristics (including location in the colorectum, histological phenotype (eg, conventional adenoma or serrated polyp) and molecular features (eg, microsatellite instability, cyclooxygenase expression)). Recent data also highlight the need for further investigation of the effect of O3FAs on the gut microbiota as a possible anti-CRC mechanism, when used either alone or in combination with other anti-CRC therapies. Overall, these data point towards a precision approach to using O3FAs for optimal prevention and treatment of CRC based on mechanistic understanding of host, tumour and gut microbiota factors that predict anticancer activity of O3FAs.
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Affiliation(s)
- Joanna Aldoori
- Gastrointestinal & Surgical Sciences, Leeds Institute of Medical Research, University of Leeds, Leeds, UK.,Hepatobiliary Surgery, St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Andrew J Cockbain
- Hepatobiliary Surgery, St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Giles J Toogood
- Hepatobiliary Surgery, St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Mark A Hull
- Gastrointestinal & Surgical Sciences, Leeds Institute of Medical Research, University of Leeds, Leeds, UK
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6
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Zhou E, Rifkin S. Colorectal Cancer and Diet: Risk Versus Prevention, Is Diet an Intervention? Gastroenterol Clin North Am 2021; 50:101-111. [PMID: 33518157 DOI: 10.1016/j.gtc.2020.10.012] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Colorectal cancer is the third most common cause of cancer in men and women in the world. Epidemiologic research approximates that half of colon cancer risk is preventable by modifiable risk factors, including diet. This article reviews prior studies involving certain food items and their relation to colorectal cancer, to elucidate whether diet can be a potential intervention.
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Affiliation(s)
- Elinor Zhou
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 431, Baltimore, MD, USA.
| | - Samara Rifkin
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Michigan School of Medicine, 1150 West Medical Center Drive, 6520 MSRB1, Ann Arbor, MI, USA
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7
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Assessing the safety of transarterial locoregional delivery of low-density lipoprotein docosahexaenoic acid nanoparticles to the rat liver. Eur J Pharm Biopharm 2020; 158:273-283. [PMID: 33242579 DOI: 10.1016/j.ejpb.2020.10.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 09/14/2020] [Accepted: 10/25/2020] [Indexed: 11/22/2022]
Abstract
Hepatic-arterial infusion (HAI) of low-density lipoprotein (LDL) nanoparticles reconstituted with docosahexaenoic acid (DHA) (LDL-DHA) has been shown in a rat hepatoma model to be a promising treatment for hepatocellular carcinoma. To date, little is known regarding the safety of HAI of LDL-DHA to the liver. Therefore, we aimed to investigate the deposition, metabolism and safety of HAI of LDL-DHA (2, 4 or 8 mg/kg) in the rat. Following HAI, fluorescent labeled LDL nanoparticles displayed a biexponential plasma concentration time curve as the particles were rapidly extracted by the liver. Overall, increasing doses of HAI of LDL-DHA was well tolerated in the rat. Body weight, plasma biochemistry and histology were all unremarkable and molecular markers of inflammation did not increase with treatment. Lipidomics analyses showed that LDL-DHA was preferentially oxidized to the anti-inflammatory mediator, protectin DX. We conclude that HAI of LDL-DHA nanoparticles is not only safe, but provides potential hepatoprotective benefits.
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8
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Zhang J, Freund MA, Culler MD, Yang R, Chen PB, Park Y, Decker EA, Zhang G. How To Stabilize ω-3 Polyunsaturated Fatty Acids (PUFAs) in an Animal Feeding Study?-Effects of the Temperature, Oxygen Level, and Antioxidant on Oxidative Stability of ω-3 PUFAs in a Mouse Diet. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2020; 68:13146-13153. [PMID: 32159344 DOI: 10.1021/acs.jafc.9b08298] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/11/2023]
Abstract
Substantial studies have shown that ω-3 polyunsaturated fatty acids (PUFAs) have various health-promoting effects; however, there are inconsistent results from animal studies that showed that ω-3 PUFAs have no effects or even detrimental effects. Emerging research suggests that oxidized ω-3 PUFAs have different effects compared to unoxidized ω-3 PUFAs; therefore, lipid oxidation of dietary ω-3 PUFAs could contribute to the mixed results of ω-3 PUFAs in animal studies. Here, we prepared an AIN-93G-based, semi-purified, powder diet, which is one of the most commonly used rodent diets in animal studies, to study the oxidative stability of fortified ω-3 PUFAs in animal feed. We found that lowering the storage temperature or the addition of a certain antioxidant, notably tert-butylhydroquinone (TBHQ), helps to stabilize ω-3 PUFAs and suppress ω-3 oxidation in the animal diet, while reducing the level of oxygen in the storage atmosphere is not very effective. The addition of 50 ppm of TBHQ in the diet inhibited 99.5 ± 0.1% formation of primary oxidation products and inhibited 96.1 ± 0.7% formation of secondary oxidation products, after 10 days of storage of the prepared diet at a typical animal-feeding experiment condition. Overall, our results highlight that ω-3 PUFAs are highly prone to lipid oxidation in a typical animal-feeding experiment, emphasizing the critical importance to stabilize ω-3 PUFAs in animal studies.
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Affiliation(s)
- Jianan Zhang
- Department of Food Science, University of Massachusetts Amherst, Amherst, Massachusetts 01003, United States
| | - Michael A Freund
- Department of Food Science, University of Massachusetts Amherst, Amherst, Massachusetts 01003, United States
| | - Mitchell D Culler
- Department of Food Science, University of Massachusetts Amherst, Amherst, Massachusetts 01003, United States
| | - Ran Yang
- Department of Food Science, University of Massachusetts Amherst, Amherst, Massachusetts 01003, United States
| | - Phoebe B Chen
- Department of Food Science, University of Massachusetts Amherst, Amherst, Massachusetts 01003, United States
| | - Yeonhwa Park
- Department of Food Science, University of Massachusetts Amherst, Amherst, Massachusetts 01003, United States
| | - Eric A Decker
- Department of Food Science, University of Massachusetts Amherst, Amherst, Massachusetts 01003, United States
| | - Guodong Zhang
- Department of Food Science, University of Massachusetts Amherst, Amherst, Massachusetts 01003, United States
- Molecular and Cellular Biology Graduate Program, University of Massachusetts Amherst, Amherst, Massachusetts 01003, United States
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9
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Tu M, Wang W, Zhang G, Hammock BD. ω-3 Polyunsaturated Fatty Acids on Colonic Inflammation and Colon Cancer: Roles of Lipid-Metabolizing Enzymes Involved. Nutrients 2020; 12:nu12113301. [PMID: 33126566 PMCID: PMC7693568 DOI: 10.3390/nu12113301] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 10/22/2020] [Accepted: 10/24/2020] [Indexed: 02/06/2023] Open
Abstract
Substantial human and animal studies support the beneficial effects of ω-3 polyunsaturated fatty acids (PUFAs) on colonic inflammation and colorectal cancer (CRC). However, there are inconsistent results, which have shown that ω-3 PUFAs have no effect or even detrimental effects, making it difficult to effectively implement ω-3 PUFAs for disease prevention. A better understanding of the molecular mechanisms for the anti-inflammatory and anticancer effects of ω-3 PUFAs will help to clarify their potential health-promoting effects, provide a scientific base for cautions for their use, and establish dietary recommendations. In this review, we summarize recent studies of ω-3 PUFAs on colonic inflammation and CRC and discuss the potential roles of ω-3 PUFA-metabolizing enzymes, notably the cytochrome P450 monooxygenases, in mediating the actions of ω-3 PUFAs.
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Affiliation(s)
- Maolin Tu
- Department of Food Science, University of Massachusetts, Amherst, MA 01002, USA; (M.T.); (G.Z.)
- Department of Food Science and Technology, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian 116034, China
| | - Weicang Wang
- Department of Entomology and Comprehensive Cancer Center, University of California, Davis, CA 95616, USA;
| | - Guodong Zhang
- Department of Food Science, University of Massachusetts, Amherst, MA 01002, USA; (M.T.); (G.Z.)
- Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, MA 01002, USA
| | - Bruce D. Hammock
- Department of Entomology and Comprehensive Cancer Center, University of California, Davis, CA 95616, USA;
- Correspondence: ; Tel.: +1-530-752-7519
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10
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Wang L, Hang D, He X, Lo CH, Wu K, Chan AT, Ogino S, Giovannucci EL, Song M. A prospective study of erythrocyte polyunsaturated fatty acids and risk of colorectal serrated polyps and conventional adenomas. Int J Cancer 2020; 148:57-66. [PMID: 32638350 DOI: 10.1002/ijc.33190] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 06/12/2020] [Accepted: 06/19/2020] [Indexed: 12/31/2022]
Abstract
The influence of polyunsaturated fatty acids (PUFAs) on risk of colorectal cancer precursors remains largely unknown. We examined the associations of erythrocyte PUFAs, including n-3 and n-6 PUFAs, with risk of colorectal conventional adenomas and serrated polyps in 4517 participants from three US prospective cohorts who had provided a blood sample and undergone at least one endoscopic examination. We calculated the multivariable odds ratios (ORs) per 1 SD increment in individual PUFAs and the ratio of n-6/n-3 PUFAs. We considered P < .005 statistically significant to account for multiple testing. During a median of 20 years of follow-up, we documented 493 conventional adenomas and 316 serrated polyps. After adjusting for various CRC risk factors, no associations for PUFAs achieved the stringent statistical significance for either conventional adenomas or serrated polyps (ORs per 1 SD ranged from 0.90 to 1.14). Some associations achieved nominal significance (P < .05), including the association of dihomogammalinolenic acid (DGLA) (20:3, n-6) with lower risk of conventional adenomas (OR = 0.91; 95% confidence interval [CI] = 0.83-1.00), total n-6 PUFAs with higher risk of proximal serrated polyps (OR = 1.32; 95% CI = 1.01-1.74) and eicosadienoic acid (20:2, n-6) and DGLA with lower risk of advanced adenomas (OR = 0.83; 95% CI = 0.71-0.97 and OR = 0.84; 95% CI = 0.72-0.98, respectively). Our findings indicate that erythrocyte PUFAs in a typical American diet are unlikely to have a substantial influence on risk of colorectal cancer precursors. The subgroup associations require further confirmation.
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Affiliation(s)
- Liang Wang
- Center of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Dong Hang
- Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Xiaosheng He
- Department of Colorectal Surgery, The Six Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Chun-Han Lo
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.,Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Kana Wu
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Andrew T Chan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.,Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.,Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Shuji Ogino
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.,Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.,Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Edward L Giovannucci
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.,Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Mingyang Song
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.,Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.,Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
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11
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Khadge S, Sharp JG, Thiele GM, McGuire TR, Talmadge JE. Fatty Acid Mediators in the Tumor Microenvironment. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1259:125-153. [PMID: 32578175 DOI: 10.1007/978-3-030-43093-1_8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Patients with cancer frequently overexpress inflammatory cytokines with an associated neutrophilia both of which may be downregulated by diets with high omega-3 polyunsaturated fatty acids (ω-3 PUFA). The anti-inflammatory activity of dietary ω-3 PUFA has been suggested to have anticancer properties and to improve survival of cancer patients. Currently, the majority of dietary research efforts do not differentiate between obesity and dietary fatty acid consumption as mediators of inflammatory cell expansion and tumor microenvironmental infiltration, initiation, and progression. In this chapter, we discuss the relationships between dietary lipids, inflammation, neoplasia and strategies to regulate these relationships. We posit that dietary composition, notably the ratio of ω-3 vs. ω-6 PUFA, regulates tumor initiation and progression and the frequency and sites of metastasis that, together, impact overall survival (OS). We focus on three broad topics: first, the role of dietary lipids in chronic inflammation and tumor initiation, progression, and regression; second, lipid mediators linking inflammation and cancer; and third, dietary lipid regulation of murine and human tumor initiation, progression, and metastasis.
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Affiliation(s)
- Saraswoti Khadge
- Department of Pathology and Microbiology and Immunology, University of Nebraska Medical Center, Omaha, NE, USA.,Vanderbilt University, Nashville, TN, USA
| | - John Graham Sharp
- Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA
| | - Geoffrey M Thiele
- Department of Pathology and Microbiology and Immunology, University of Nebraska Medical Center, Omaha, NE, USA.,Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA.,Veteran Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA
| | - Timothy R McGuire
- Department of Pharmacy Practice, University of Nebraska Medical Center, Omaha, NE, USA
| | - James E Talmadge
- Department of Pathology and Microbiology and Immunology, University of Nebraska Medical Center, Omaha, NE, USA. .,Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
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12
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Song M, Lee IM, Manson JE, Buring JE, Dushkes R, Gordon D, Walter J, Wu K, Chan AT, Ogino S, Fuchs CS, Meyerhardt JA, Giovannucci EL. Effect of Supplementation With Marine ω-3 Fatty Acid on Risk of Colorectal Adenomas and Serrated Polyps in the US General Population: A Prespecified Ancillary Study of a Randomized Clinical Trial. JAMA Oncol 2020; 6:108-115. [PMID: 31750855 DOI: 10.1001/jamaoncol.2019.4587] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Importance Marine ω-3 fatty acid has been suggested to protect against colorectal cancer. Objective To assess the effect of daily marine ω-3 fatty acid supplementation on the risk of colorectal cancer precursors, including conventional adenomas and serrated polyps. Design, Setting, and Participants This study was a prespecified ancillary study of the placebo-controlled randomized clinical trial VITAL (Vitamin D and Omega-3 Trial). An intention-to-treat analysis was used to examine the effect of daily marine ω-3 supplements among 25 871 adults in the US general population (including 5106 African American persons) free of cancer and cardiovascular disease at enrollment. Randomization was from November 2011 to March 2014, and intervention ended as planned on December 31, 2017. Interventions Marine ω-3 fatty acid, 1 g daily (which included eicosapentaenoic acid, 460 mg, and docosahexaenoic acid, 380 mg) and vitamin D3 (2000 IU daily) supplements. Main Outcomes and Measures Risk of conventional adenomas (including tubular adenoma, tubulovillous adenoma, villous adenoma, and adenoma with high-grade dysplasia) or serrated polyps (including hyperplastic polyp, traditional serrated adenoma, and sessile serrated polyp). In a subset of participants who reported receiving a diagnosis of polyp on follow-up questionnaires, endoscopic and pathologic records were obtained to confirm the diagnosis. Odds ratios (ORs) and 95% CIs were calculated using logistic regression, after adjusting for age, sex, vitamin D treatment assignment, and use of endoscopy. Secondary analyses were performed according to polyp features and participants' characteristics. Results The demographic characteristics of participants at randomization were well balanced between the treatment and placebo groups; for example, 50.6% vs 50.5% were women, and 19.7% vs 19.8% were African American persons were included in each group. The mean (SD) age was 67.1 (7.1) years in the placebo group and 67.2 (7.1) in the ω-3 treatment group. During a median follow-up of 5.3 years (range, 3.8-6.1 years), 294 cases of conventional adenomas were documented in the ω-3 group and 301 in the control group (multivariable OR, 0.98; 95% CI, 0.83-1.15) (1:1 ratio between number of cases and number of participants). In addition, 174 cases of serrated polyps were documented in the ω-3 group and 167 in the control group (OR, 1.05; 95% CI, 0.84-1.29). Null associations were found for polyp subgroups according to size, location, multiplicity, or histology. In secondary analyses, marine ω-3 treatment appeared to be associated with lower risk of conventional adenomas among individuals with low plasma levels of ω-3 index at baseline (OR, 0.76; 95% CI, 0.57-1.02; P = .03 for interaction by ω-3 index). A beneficial association of supplementation was also noted in the African American population (OR, 0.59; 95% CI, 0.35-1.00) but not in other racial/ethnic groups (P = .11 for interaction). Conclusions and Relevance Supplementation with marine ω-3 fatty acids, 1 g per day, was not associated with reduced risk of colorectal cancer precursors. A potential benefit of this supplementation for individuals with low baseline ω-3 levels or for African American persons requires further confirmation. Trial Registration ClinicalTrials.gov identifier: NCT01169259.
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Affiliation(s)
- Mingyang Song
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Clinical and Translational Epidemiology Unit, Mongan Institute, Massachusetts General Hospital, Harvard Medical School, Boston.,Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston
| | - I-Min Lee
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
| | - JoAnn E Manson
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.,Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Julie E Buring
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
| | - Rimma Dushkes
- Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
| | - David Gordon
- Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
| | - Joseph Walter
- Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
| | - Kana Wu
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Andrew T Chan
- Clinical and Translational Epidemiology Unit, Mongan Institute, Massachusetts General Hospital, Harvard Medical School, Boston.,Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston.,Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.,Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge
| | - Shuji Ogino
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge.,Department of Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.,Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Charles S Fuchs
- Yale Cancer Center, New Haven, Connecticut.,Department of Medicine, Yale School of Medicine, New Haven, Connecticut.,Smilow Cancer Hospital, New Haven, Connecticut
| | - Jeffrey A Meyerhardt
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
| | - Edward L Giovannucci
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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13
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Haidari F, Abiri B, Iravani M, Ahmadi-Angali K, Vafa M. Effects of Vitamin D and Omega-3 Fatty Acids Co-Supplementation on Inflammatory Factors and Tumor Marker CEA in Colorectal Cancer Patients Undergoing Chemotherapy: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Nutr Cancer 2019; 72:948-958. [PMID: 32441198 DOI: 10.1080/01635581.2019.1659380] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Objectives: This study aimed to investigate the effects of vitamin D and omega-3 fatty acids co-supplementation on inflammatory factors and tumor marker CEA in colorectal cancer patients undergoing chemotherapy.Methods: In this study, 81 patients with stage ӀӀ or ӀӀӀ colorectal cancer were randomly assigned into four groups: (1) control: receiving a vitamin D placebo, weekly + two omega-3 fatty acid placebo capsules, daily; (2) omega-3 fatty acid, receiving two omega-3 fatty acid capsules (each capsule containing 330 mg of omega-3 fatty acids), daily + a vitamin D placebo, weekly; (3) vitamin D, receiving a 50,000 IU vitamin D soft gel, weekly + two omega-3 fatty acid placebo capsules, daily; (4) co-supplementation, receiving a 50,000 IU vitamin D soft gel, weekly + two omega-3 fatty acids capsules, for 8 weeks. Before and after the intervention, serum levels of 25(OH)D, TNF-α, IL-1β, IL-6, IL-8, NF-kB activity, and tumor marker CEA, were measured.Results: After 8 weeks of intervention, patients who received combined vitamin D and omega-3 fatty acids supplements compared with omega-3, vitamin D, and placebo had significantly decreased TNF-α, and IL-1β (P < .05). In addition, serum levels of TNF-α, IL-1β, IL-6, IL-8, and tumor marker CEA were decreased significantly in omega-3, vitamin D, and co-supplementation of them, compared with baseline. NF-kB activity was decreased significantly in vitamin D and co-supplementation groups, compared with baseline. Regarding CEA, there was no significant difference between the four groups at the end of intervention (P > .05).Conclusion: Results show that co-supplementation of vitamin D and omega-3 fatty acids co-supplementation, in colorectal cancer patients have beneficial impacts on inflammation and tumor marker CEA.
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Affiliation(s)
- Fatemeh Haidari
- Department of Nutrition, Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Behnaz Abiri
- Department of Nutrition, Faculty of Paramedicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Masood Iravani
- Department of Medical Oncology and Hematology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Kambiz Ahmadi-Angali
- Faculty of Public Health, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mohammadreza Vafa
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran.,Pediatric Growth and Development Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran Iran
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14
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Austin Pickens C, Yin Z, Sordillo LM, Fenton JI. Arachidonic acid-derived hydroxyeicosatetraenoic acids are positively associated with colon polyps in adult males: a cross-sectional study. Sci Rep 2019; 9:12033. [PMID: 31427689 PMCID: PMC6700170 DOI: 10.1038/s41598-019-48381-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2019] [Accepted: 07/30/2019] [Indexed: 01/25/2023] Open
Abstract
Oxylipids are potent lipid mediators associated with inflammation-induced colon carcinomas and colon tumor survival. Therefore, oxylipid profiles may be useful as novel biomarkers of colon polyp presence. The aim of this study was to investigate the relationship between plasma non-esterified oxylipids and the presence of colon polyps. A total of 123 Caucasian men, ages 48 to 65, were categorized into three groups: those with no polyps, those with one or more hyperplastic polyps, and those with one or more adenomas. Plasma non-esterified oxylipids were analyzed using solid phase extraction and quantified using a targeted HPLC tandem mass spectrometric analysis. Statistical analyses included Kruskal-Wallis one-way ANOVA with Dunn's test for multiple comparison and generalized linear models to adjust for confounding factors such as age, anthropometrics, and smoking status. In general, monohydroxy omega-6-derived oxylipids were significantly increased in those with polyps. Concentrations of 5-hydroxyeicosatetraenoic acid (HETE) and 11-HETE were significantly higher in those with hyperplastic polyps and adenomas compared to those with no polyps. Arachidonic acid-derived HETEs were significantly associated with colon polyp types, even after adjusting for age, smoking, and body mass index or waist circumference in regression models. Since many of these oxylipids are formed through oxygenation by lipoxygenases (i.e., 5-, 12-, and 15-HETE, and 15- hydroxyeicosatrienoic acid [HETrE]) or auto-oxidative reactions (i.e., 11-HETE), this may indicate that lipoxygenase activity and lipid peroxidation are increased in those with colon polyps. In addition, since oxylipids such as 5-, 12-, and 15-HETE are signaling molecules involved in inflammation regulation, these oxylipids may have important functions in inflammation-associated polyp presence. Future studies should be performed in a larger cohorts to investigate if these oxylipids are useful as potential biomarkers of colon polyps.
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Affiliation(s)
- C Austin Pickens
- Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, USA
| | - Zhe Yin
- Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, USA
| | - Lorraine M Sordillo
- College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA
| | - Jenifer I Fenton
- Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, USA.
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Haidari F, Abiri B, Iravani M, Ahmadi-Angali K, Vafa M. Randomized Study of the Effect of Vitamin D and Omega-3 Fatty Acids Cosupplementation as Adjuvant Chemotherapy on Inflammation and Nutritional Status in Colorectal Cancer Patients. J Diet Suppl 2019; 17:384-400. [DOI: 10.1080/19390211.2019.1600096] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Affiliation(s)
- Fatemeh Haidari
- Department of Nutrition, Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Behnaz Abiri
- Department of Nutrition, Faculty of Paramedicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | | | - Kambiz Ahmadi-Angali
- Faculty of Public Health, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mohammadreza Vafa
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
- Pediatric Growth and Development Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
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16
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Dąbrowska M, Sokalska K, Gumułka P, Binert-Kusztal Ż, Starek M. Quantification of omega-3 fatty acids in dietary supplements and cooking products available on the polish market by thin-layer chromatography–densitometry. JPC-J PLANAR CHROMAT 2019. [DOI: 10.1556/1006.2019.32.1.2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Affiliation(s)
- Monika Dąbrowska
- Department of Inorganic and Analytical Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Str, 30-688 Kraków, Poland
| | - Kinga Sokalska
- Department of Inorganic and Analytical Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Str, 30-688 Kraków, Poland
| | - Paweł Gumułka
- Department of Inorganic and Analytical Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Str, 30-688 Kraków, Poland
| | - Żaneta Binert-Kusztal
- Department of Inorganic and Analytical Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Str, 30-688 Kraków, Poland
| | - Małgorzata Starek
- Department of Inorganic and Analytical Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Str, 30-688 Kraków, Poland
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17
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Zhang Y, Zhang B, Dong L, Chang P. Potential of Omega-3 Polyunsaturated Fatty Acids in Managing Chemotherapy- or Radiotherapy-Related Intestinal Microbial Dysbiosis. Adv Nutr 2019; 10:133-147. [PMID: 30566596 PMCID: PMC6370266 DOI: 10.1093/advances/nmy076] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2018] [Accepted: 09/10/2018] [Indexed: 02/06/2023] Open
Abstract
Chemotherapy- or radiotherapy-related intestinal microbial dysbiosis is one of the main causes of intestinal mucositis. Cases of bacterial translocation into peripheral blood and subsequent sepsis occur as a result of dysfunction in the intestinal barrier. Evidence from recent studies depicts the characteristics of chemotherapy- or radiotherapy-related intestinal microbial dysbiosis, which creates an imbalance between beneficial and harmful bacteria in the gut. Decreases in beneficial bacteria can lead to a weakening of the resistance of the gut to harmful bacteria, resulting in robust activation of proinflammatory signaling pathways. For example, lipopolysaccharide (LPS)-producing bacteria activate the nuclear transcription factor-κB signaling pathway through binding with Toll-like receptor 4 on stressed epithelial cells, subsequently leading to secretion of proinflammatory cytokines. Nevertheless, various studies have found that the omega-3 (n-3) polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid and eicosapentaenoic acid can reverse intestinal microbial dysbiosis by increasing beneficial bacteria species, including Lactobacillus, Bifidobacterium, and butyrate-producing bacteria, such as Roseburia and Coprococcus. In addition, the n-3 PUFAs decrease the proportions of LPS-producing and mucolytic bacteria in the gut, and they can reduce inflammation as well as oxidative stress. Importantly, the n-3 PUFAs also exert anticancer effects in colorectal cancers. In this review, we summarize the characteristics of chemotherapy- or radiotherapy-related intestinal microbial dysbiosis and introduce the contributions of dysbiosis to the pathogenesis of intestinal mucositis. Next, we discuss how n-3 PUFAs could alleviate chemotherapy- or radiotherapy-related intestinal microbial dysbiosis. This review provides new insights into the clinical administration of n-3 PUFAs for the management of chemotherapy- or radiotherapy-related intestinal microbial dysbiosis.
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Affiliation(s)
- Yue Zhang
- Department of Radiation Oncology, First Bethune Hospital of Jilin University, ChangChun, China
| | - Boyan Zhang
- Orthopedic Medical Center, The Second Hospital of Jilin University, ChangChun, China
| | - Lihua Dong
- Department of Radiation Oncology, First Bethune Hospital of Jilin University, ChangChun, China,Address correspondence to LD (e-mail: )
| | - Pengyu Chang
- Department of Radiation Oncology, First Bethune Hospital of Jilin University, ChangChun, China,Address correspondence to PC (e-mail: )
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18
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Isom CA, Shrubsole MJ, Cai Q, Smalley WE, Ness RM, Zheng W, Murff HJ. Arachidonic acid and colorectal adenoma risk: a Mendelian randomization study. Clin Epidemiol 2018; 11:17-22. [PMID: 30588120 PMCID: PMC6302799 DOI: 10.2147/clep.s186883] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Previous studies have shown a link between increased dietary intake of arachidonic acid (ARA) and colorectal neoplasms. It has been shown that erythrocyte phospholipid membrane concentrations of ARA are strongly determined by genetic variation. Fatty acid desaturase (FADS) controls the rate limiting step in ARA production, and FADS variant rs174537 has been shown to be responsible for up to 18.6% of the variation seen. To determine if a causal association exists between erythrocyte membrane ARA concentrations and colorectal adenomas, we conducted a Mendelian randomization (MR) analysis using rs174537 as an instrumental variable (IV). MR analysis was chosen because it is less susceptible to bias and confounding. PATIENTS AND METHODS A case-control study was performed using the Tennessee Colorectal Polyps Study. Patients were matched on age, gender, race, facility site, and year of colonoscopy. Cases were defined as any colorectal adenoma on colonoscopy (n=909) and controls were polyp free (n=855). A two-stage logistic regression was conducted using rs174537 as the IV with the dependent variable being the presence of a colorectal adenoma on colonoscopy. RESULTS Cases were older (59 vs 57 years of age, P<0.0001), and more likely to use alcohol (47.4% vs 19.8%, P=0.001) and to smoke (77.0% vs 66.9%, P<0.0001). There was no statistically significant difference in: age, sex, alcohol use, body mass index (BMI), or NSAID use when stratified by the rs174537 alleles. Genotype was strongly associated with erythrocyte membrane ARA concentrations (P<0.0001). We found no evidence of an association between our IV (rs174537) and colorectal adenomas (P=0.41). CONCLUSION In our MR study increased erythrocyte ARA concentrations were not associated with the risk of colorectal adenomas.
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Affiliation(s)
- Chelsea A Isom
- Department of General Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Martha J Shrubsole
- Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN, USA
- GRECC, Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA,
| | - Qiuyin Cai
- Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Walter E Smalley
- Department of Health Policy, Vanderbilt University Medical Center, Nashville, TN, USA
- Division of Gastroenterology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Reid M Ness
- Division of Gastroenterology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Wei Zheng
- Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN, USA
- GRECC, Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA,
| | - Harvey J Murff
- GRECC, Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA,
- Division of General Internal Medicine and Public Health, Vanderbilt University Medical Center, Nashville, TN, USA,
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19
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Immune regulation and anti-cancer activity by lipid inflammatory mediators. Int Immunopharmacol 2018; 65:580-592. [PMID: 30447537 DOI: 10.1016/j.intimp.2018.10.026] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Revised: 10/02/2018] [Accepted: 10/17/2018] [Indexed: 12/19/2022]
Abstract
Rodent and clinical studies have documented that myeloid cell infiltration of tumors is associated with poor outcomes, neutrophilia and lymphocytopenia. This contrasts with increased lymphocyte infiltration of tumors, which is correlated with improved outcomes. Lifestyle parameters, such as obesity and diets with high levels of saturated fat and/or omega (ω)-6 polyunsaturated fatty acids (PUFAs), can influence these inflammatory parameters, including an increase in extramedullary myelopoiesis (EMM). While tumor secretion of growth factors (GFs) and chemokines regulate tumor-immune-cell crosstalk, lifestyle choices also contribute to inflammation, abnormal pathology and leukocyte infiltration of tumors. A relationship between obesity and high-fat diets (notably saturated fats in Western diets) and inflammation, tumor incidence, metastasis and poor outcomes is generally accepted. However, the mechanisms of dietary promotion of an inflammatory microenvironment and targeted drugs to inhibit the clinical sequelae are poorly understood. Thus, modifications of obesity and dietary fat may provide preventative or therapeutic approaches to control tumor-associated inflammation and disease progression. Currently, the majority of basic and clinical research does not differentiate between obesity and fatty acid consumption as mediators of inflammatory and neoplastic processes. In this review, we discuss the relationships between dietary PUFAs, inflammation and neoplasia and experimental strategies to improve our understanding of these relationships. We conclude that dietary composition, notably the ratio of ω-3 vs ω-6 PUFA regulates tumor growth and the frequency and sites of metastasis that together, impact overall survival (OS) in mice.
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20
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Pandurangan AK, Divya T, Kumar K, Dineshbabu V, Velavan B, Sudhandiran G. Colorectal carcinogenesis: Insights into the cell death and signal transduction pathways: A review. World J Gastrointest Oncol 2018; 10:244-259. [PMID: 30254720 PMCID: PMC6147765 DOI: 10.4251/wjgo.v10.i9.244] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2018] [Revised: 06/05/2018] [Accepted: 06/28/2018] [Indexed: 02/05/2023] Open
Abstract
Colorectal carcinogenesis (CRC) imposes a major health burden in developing countries. It is the third major cause of cancer deaths. Despite several treatment strategies, novel drugs are warranted to reduce the severity of this disease. Adenomatous polyps in the colon are the major culprits in CRC and found in 45% of cancers, especially in patients 60 years of age. Inflammatory polyps are currently gaining attention in CRC, and a growing body of evidence denotes the role of inflammation in CRC. Several experimental models are being employed to investigate CRC in animals, which include the APCmin/+ mouse model, Azoxymethane, Dimethyl hydrazine, and a combination of Dextran sodium sulphate and dimethyl hydrazine. During CRC progression, several signal transduction pathways are activated. Among the major signal transduction pathways are p53, Transforming growth factor beta, Wnt/β-catenin, Delta Notch, Hippo signalling, nuclear factor erythroid 2-related factor 2 and Kelch-like ECH-associated protein 1 pathways. These signalling pathways collaborate with cell death mechanisms, which include apoptosis, necroptosis and autophagy, to determine cell fate. Extensive research has been carried out in our laboratory to investigate these signal transduction and cell death mechanistic pathways in CRC. This review summarizes CRC pathogenesis and the related cell death and signal transduction pathways.
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Affiliation(s)
- Ashok kumar Pandurangan
- Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India
- School of Life sciences, B.S. Abdur Rahman Crescent Institute of Science and Technology, Chennai 600048, India
| | - Thomas Divya
- Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India
| | - Kalaivani Kumar
- School of Life sciences, B.S. Abdur Rahman Crescent Institute of Science and Technology, Chennai 600048, India
| | - Vadivel Dineshbabu
- Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India
| | - Bakthavatchalam Velavan
- Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India
| | - Ganapasam Sudhandiran
- Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India
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21
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Pickens CA, Albuquerque Pereira MDF, Fenton JI. Long-chain ω-6 plasma phospholipid polyunsaturated fatty acids and association with colon adenomas in adult men: a cross-sectional study. Eur J Cancer Prev 2018; 26:497-505. [PMID: 27768609 DOI: 10.1097/cej.0000000000000312] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Dietary lipid intake can be associated with an increased risk for colorectal cancer depending on its composition. Carcinogenesis alters lipid metabolism to facilitate cell growth and survival. For instance, metabolites of polyunsaturated fatty acids (PUFAs) are associated with increasing colon cell proliferation. Moreover, precancerous colon lesions (i.e. adenomas) increase the risk for colorectal cancer. In this study, we investigated associations between plasma PUFAs and the number of colon polyps and polyp type (i.e. hyperplastic and adenoma). Healthy male participants (n=126) of 48-65 years of age were recruited before a routine colonoscopy screening. Plasma phospholipid (PPL) PUFAs were isolated by means of solid phase extraction and methylated. Fatty acid methyl esters were analyzed using gas chromatography. Factor analysis was used to cluster PUFAs into groups, and then generated factors and individual PUFAs were analyzed using polytomous logistic regression. In our age-adjusted and smoking-adjusted polytomous logistic regression, for each unit increase in PPL docosatetraenoic acid (DTA), individuals were 1.43 (1.00-2.06) and 1.33 (0.99-1.80) times more likely to have hyperplastic polyps and adenomas rather than no polyps, respectively. In our factor analysis, high PPL ω-6 PUFA and trans-fatty acid loading scores were associated with increased odds of adenoma presence rather than no polyps. Increases in long-chain PPL ω-6 PUFAs are associated with an increased risk for adenomas. As relative levels of DTA increase in PPLs, individuals had increased odds of having hyperplastic polyps and adenomas. Elevated conversion of ω-6 PUFAs to longer-chain ω-6s such as DTA may indicate altered PUFA metabolism at the tissue level.
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Affiliation(s)
- Charles A Pickens
- Department of Food Science and Human Nutrition, Michigan State University, East Lansing, Michigan, USA
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Wang W, Yang H, Johnson D, Gensler C, Decker E, Zhang G. Chemistry and biology of ω-3 PUFA peroxidation-derived compounds. Prostaglandins Other Lipid Mediat 2017; 132:84-91. [DOI: 10.1016/j.prostaglandins.2016.12.004] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2016] [Revised: 12/21/2016] [Accepted: 12/30/2016] [Indexed: 12/15/2022]
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Hou TY, Davidson LA, Kim E, Fan YY, Fuentes NR, Triff K, Chapkin RS. Nutrient-Gene Interaction in Colon Cancer, from the Membrane to Cellular Physiology. Annu Rev Nutr 2017; 36:543-70. [PMID: 27431370 DOI: 10.1146/annurev-nutr-071715-051039] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The International Agency for Research on Cancer recently released an assessment classifying red and processed meat as "carcinogenic to humans" on the basis of the positive association between increased consumption and risk for colorectal cancer. Diet, however, can also decrease the risk for colorectal cancer and be used as a chemopreventive strategy. Bioactive dietary molecules, such as n-3 polyunsaturated fatty acids, curcumin, and fermentable fiber, have been proposed to exert chemoprotective effects, and their molecular mechanisms have been the focus of research in the dietary/chemoprevention field. Using these bioactives as examples, this review surveys the proposed mechanisms by which they exert their effects, from the nucleus to the cellular membrane. In addition, we discuss emerging technologies involving the culturing of colonic organoids to study the physiological effects of dietary bioactives. Finally, we address future challenges to the field regarding the identification of additional molecular mechanisms and other bioactive dietary molecules that can be utilized in our fight to reduce the incidence of colorectal cancer.
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Affiliation(s)
- Tim Y Hou
- Program in Integrative Nutrition and Complex Diseases, Texas A&M University, College Station, Texas 77843; .,Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843
| | - Laurie A Davidson
- Program in Integrative Nutrition and Complex Diseases, Texas A&M University, College Station, Texas 77843; .,Department of Nutrition and Food Science, Texas A&M University, College Station, Texas 77843.,Center for Translational Environmental Health Research, Texas A&M University, College Station, Texas 77843
| | - Eunjoo Kim
- Program in Integrative Nutrition and Complex Diseases, Texas A&M University, College Station, Texas 77843; .,Department of Molecular and Cellular Medicine, Texas A&M University, College Station, Texas 77843
| | - Yang-Yi Fan
- Program in Integrative Nutrition and Complex Diseases, Texas A&M University, College Station, Texas 77843; .,Department of Nutrition and Food Science, Texas A&M University, College Station, Texas 77843
| | - Natividad R Fuentes
- Program in Integrative Nutrition and Complex Diseases, Texas A&M University, College Station, Texas 77843; .,Faculty of Toxicology, Texas A&M University, College Station, Texas 77843
| | - Karen Triff
- Program in Integrative Nutrition and Complex Diseases, Texas A&M University, College Station, Texas 77843;
| | - Robert S Chapkin
- Program in Integrative Nutrition and Complex Diseases, Texas A&M University, College Station, Texas 77843; .,Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843.,Department of Nutrition and Food Science, Texas A&M University, College Station, Texas 77843.,Faculty of Toxicology, Texas A&M University, College Station, Texas 77843.,Center for Translational Environmental Health Research, Texas A&M University, College Station, Texas 77843
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24
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Wang W, Yang J, Nimiya Y, Lee KSS, Sanidad K, Qi W, Sukamtoh E, Park Y, Liu Z, Zhang G. ω-3 Polyunsaturated fatty acids and their cytochrome P450-derived metabolites suppress colorectal tumor development in mice. J Nutr Biochem 2017; 48:29-35. [PMID: 28672272 DOI: 10.1016/j.jnutbio.2017.06.006] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Revised: 06/01/2017] [Accepted: 06/06/2017] [Indexed: 12/26/2022]
Abstract
Many studies have shown that dietary intake of ω-3 polyunsaturated fatty acids (PUFAs) reduces the risks of colorectal cancer; however, the underlying mechanisms are not well understood. Here we used a LC-MS/MS-based lipidomics to explore the role of eicosanoid signaling in the anti-colorectal cancer effects of ω-3 PUFAs. Our results showed that dietary feeding of ω-3 PUFAs-rich diets suppressed growth of MC38 colorectal tumor, and modulated profiles of fatty acids and eicosanoid metabolites in C57BL/6 mice. Notably, we found that dietary feeding of ω-3 PUFAs significantly increased levels of epoxydocosapentaenoic acids (EDPs, metabolites of ω-3 PUFA produced by cytochrome P450 enzymes) in plasma and tumor tissue of the treated mice. We further showed that systematic treatment with EDPs (dose=0.5 mg/kg per day) suppressed MC38 tumor growth in mice, with reduced expressions of pro-oncogenic genes such as C-myc, Axin2, and C-jun in tumor tissues. Together, these results support that formation of EDPs might contribute to the anti-colorectal cancer effects of ω-3 PUFAs.
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Affiliation(s)
- Weicang Wang
- Department of Food Science, University of Massachusetts, Amherst, MA
| | - Jun Yang
- Department of Entomology and Nematology, University of California, Davis, CA
| | - Yoshiki Nimiya
- Department of Food Science, University of Massachusetts, Amherst, MA; Department of Food Science and Technology, Tokyo University of Marine Science and Technology, Tokyo, Japan
| | | | - Katherine Sanidad
- Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, MA
| | - Weipeng Qi
- Department of Food Science, University of Massachusetts, Amherst, MA
| | - Elvira Sukamtoh
- Department of Food Science, University of Massachusetts, Amherst, MA
| | - Yeonhwa Park
- Department of Food Science, University of Massachusetts, Amherst, MA
| | - Zhenhua Liu
- Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, MA; Department of Nutrition, University of Massachusetts, Amherst, MA
| | - Guodong Zhang
- Department of Food Science, University of Massachusetts, Amherst, MA; Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, MA.
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Rifkin SB, Shrubsole MJ, Cai Q, Smalley WE, Ness RM, Swift LL, Zheng W, Murff HJ. PUFA levels in erythrocyte membrane phospholipids are differentially associated with colorectal adenoma risk. Br J Nutr 2017; 117:1615-1622. [PMID: 28660850 PMCID: PMC5891121 DOI: 10.1017/s0007114517001490] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Dietary intake of PUFA has been associated with colorectal neoplasm risk; however, results from observational studies have been inconsistent. Most prior studies have utilised self-reported dietary measures to assess fatty acid exposure which might be more susceptible to measurement error and biases compared with biomarkers. The purpose of this study was to determine whether erythrocyte phospholipid membrane PUFA percentages are associated with colorectal adenoma risk. We included data from 904 adenoma cases and 835 polyp-free controls who participated in the Tennessee Colorectal Polyp Study, a large colonoscopy-based case-control study. Erythrocyte membrane PUFA percentages were measured using GC. Conditional logistic regression was used to calculate adjusted OR for risk of colorectal adenomas with erythrocyte membrane PUFA. Higher erythrocyte membrane percentages of arachidonic acid was associated with an increased risk of colorectal adenomas (adjusted OR 1·66; 95 % CI 1·05, 2·62, P trend=0·02) comparing the highest tertile to the lowest tertile. The effect size for arachidonic acid was more pronounced when restricting the analysis to advanced adenomas only. Higher erythrocyte membrane EPA percentages were associated with a trend towards a reduced risk of advanced colorectal adenomas (P trend=0·05). Erythrocyte membrane arachidonic acid percentages are associated with an increased risk of colorectal adenomas.
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Affiliation(s)
- Samara B Rifkin
- 1Division of Gastroenterology and Hepatology,Johns Hopkins University School of Medicine,1800 Orleans Street,Baltimore, MD 21287,USA
| | - Martha J Shrubsole
- 2Division of Epidemiology,Vanderbilt University Medical Center,2525 West End Avenue,Suite 800,Nashville, TN 37203,USA
| | - Qiuyin Cai
- 2Division of Epidemiology,Vanderbilt University Medical Center,2525 West End Avenue,Suite 800,Nashville, TN 37203,USA
| | - Walter E Smalley
- 4Department of Health Policy,Vanderbilt University Medical Center,2525 West End Avenue,Suite 1200, Nashville, TN 37203,USA
| | - Reid M Ness
- 5Division of Gastroenterology,Vanderbilt University Medical Center,1211 Medical Center Drive,Nashville, TN 37232,USA
| | - Larry L Swift
- 6Department of Pathology, Microbiology and Immunology,Vanderbilt University Medical Center,1211 Medical Center Drive,Nashville, TN 37232,USA
| | - Wei Zheng
- 2Division of Epidemiology,Vanderbilt University Medical Center,2525 West End Avenue,Suite 800,Nashville, TN 37203,USA
| | - Harvey J Murff
- 3Geriatric Research Education and Clinical Center (GRECC),Department of Veterans Affairs,Tennessee Valley Healthcare System,1310 24th Avenue S,Nashville, TN 37212,USA
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Bailie L, Loughrey MB, Coleman HG. Lifestyle Risk Factors for Serrated Colorectal Polyps: A Systematic Review and Meta-analysis. Gastroenterology 2017; 152:92-104. [PMID: 27639804 DOI: 10.1053/j.gastro.2016.09.003] [Citation(s) in RCA: 131] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2016] [Revised: 08/18/2016] [Accepted: 09/21/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Certain subsets of colorectal serrated polyps (SP) have malignant potential. We performed a systematic review and meta-analysis to investigate the association between modifiable lifestyle factors and risk for SPs. METHODS We conducted a systematic search of Medline, Embase, and Web of Science for observational or interventional studies that contained the terms risk or risk factor, and serrated or hyperplastic, and polyps or adenomas, and colorectal (or synonymous terms), published by March 2016. Titles and abstracts of identified articles were independently reviewed by at least 2 reviewers. Adjusted relative risk (RR) and 95% confidence interval (CI) were combined using random effects meta-analyses to assess the risk of SP, when possible. RESULTS We identified 43 studies of SP risk associated with 7 different lifestyle factors: smoking, alcohol, body fatness, diet, physical activity, medication, and hormone-replacement therapy. When we compared the highest and lowest categories of exposure, factors we found to significantly increase risk for SP included tobacco smoking (RR, 2.47; 95% CI, 2.12-2.87), alcohol intake (RR, 1.33; 95% CI, 1.17-1.52), body mass index (RR, 1.40; 95% CI, 1.22-1.61), and high intake of fat or meat. Direct associations for smoking and alcohol, but not body fat, tended to be stronger for sessile serrated adenomas/polyps than hyperplastic polyps. In contrast, factors we found to significantly decrease risks for SP included use of nonsteroidal anti-inflammatory drugs (RR, 0.77; 95% CI, 0.65-0.92) or aspirin (RR, 0.81; 95% CI, 0.67-0.99), as well as high intake of folate, calcium, or fiber. No significant associations were detected between SP risk and physical activity or hormone replacement therapy. CONCLUSIONS Several lifestyle factors, most notably smoking and alcohol, are associated with SP risk. These findings enhance our understanding of mechanisms of SP development and indicate that risk of serrated pathway colorectal neoplasms could be reduced with lifestyle changes.
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Affiliation(s)
- Lesley Bailie
- Cancer Epidemiology and Health Services Research Group, Centre for Public Health, Queens University Belfast, Belfast, Northern Ireland
| | - Maurice B Loughrey
- Department of Pathology, Royal Victoria Hospital, Belfast Health and Social Care Trust, Belfast, Northern Ireland
| | - Helen G Coleman
- Cancer Epidemiology and Health Services Research Group, Centre for Public Health, Queens University Belfast, Belfast, Northern Ireland.
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Altobelli E, Angeletti PM, Latella G. Role of Urinary Biomarkers in the Diagnosis of Adenoma and Colorectal Cancer: A Systematic Review and Meta-Analysis. J Cancer 2016; 7:1984-2004. [PMID: 27877214 PMCID: PMC5118662 DOI: 10.7150/jca.16244] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2016] [Accepted: 07/16/2016] [Indexed: 12/23/2022] Open
Abstract
The growing interest in enhancing and spreading colorectal cancer (CRC) screening has been stimulating the exploration of novel biomarkers with greater sensitivity and specificity than immunochemical faecal occult blood test (iFOBT). The present study provides i) a systematic review of the urinary biomarkers that have been tested to achieve early CRC diagnosis and assess the risk of colorectal adenoma and adenocarcinoma, and ii) a meta-analysis of the data regarding the urinary prostaglandin (PG) metabolite PGE-M. As regard to gene markers, we found significantly different percent methylation of the vimentin gene in CRC patients and healthy controls (HC) (p<0.0001). Respect to metabolism of nitrogenous bases, cytidine, 1-methyladenosine, and adenosine, have higher concentrations in CRC patients than in HC (respectively, p<0.01, p=0.01, and p<0.01). As regard to spermine we found that N1,N12 diacetyl spermine (DiAcSpm) and N1, N8 diacetylspermidine (DiAcSpd) were significantly higher in CRC than in HC (respectively p=0.01 and p<0.01). Respect to PGE-M, levels were higher in CRC than in those with multiple polyposis (p<0.006) and HC subjects (p<0.0004). PGE-M seems to be the most interesting and promising urinary marker for CRC and adenoma risk assessment and for CRC screening. In conclusion, evidence suggests that urinary biomarker could have a potential role as urinary biomarkers in the diagnosis of colorectal cancer. Particularly, PGE-M seems to be the most promising urinary marker for CRC early detection.
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Affiliation(s)
- Emma Altobelli
- Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
- Epidemiology and Biostatistics Unit, AUSL Teramo, University of L'Aquila, L'Aquila, Italy
| | - Paolo Matteo Angeletti
- Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
| | - Giovanni Latella
- Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
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Fabian CJ, Kimler BF. Marine-derived omega-3 fatty acids: fishing for clues for cancer prevention. Am Soc Clin Oncol Educ Book 2015:97-101. [PMID: 23714467 DOI: 10.14694/edbook_am.2013.33.97] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Omega-3 fatty acids (FA) are polyunsaturated essential FA with anti-inflammatory properties. The most potent are the marine-derived eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which counteract the pro-inflammatory omega-6 FA. Americans take in an average of only 100 mg of EPA plus DHA per day resulting in a low omega-3:omega-6 intake ratio of 1:10 favoring inflammation. Cohort and/or case control studies suggest EPA and DHA are promising for breast, colon, and prostate cancer risk reduction. Mechanistic studies largely in preclinical models suggest EPA and DHA reduce synthesis of prostaglandin E2 and other inflammatory cytokines, decrease aromatase activity and proliferation, promote differentiation and apoptosis, and enhance insulin sensitivity. Animal models using 7% to 20% omega-3 added to chow are promising; however, this amount of omega-3 in a diet is unlikely to be acceptable to humans. The optimal EPA:DHA ratio or the lowest effective dose of EPA and DHA for cancer prevention is unclear, but it is likely to be more than 600 mg/day, which is six times the average American intake. Most phase II prevention trials use 1 to 3.3 g of EPA and DHA, which is safe and well tolerated. Two grams of EPA was associated with fewer polyps in individuals with familial adenomatous polyposis in a randomized, placebo-controlled trial. Identification of serum risk biomarkers modulated by EPA and DHA in healthy humans has remained elusive, but phase II prevention trials with tissue obtained for risk and response biomarkers are ongoing.
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Affiliation(s)
- Carol J Fabian
- From the Departments of Internal Medicine and Radiation Oncology, University of Kansas Medical Center, Kansas City, KS
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29
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Omega-3 Polyunsaturated Fatty Acids: The Way Forward in Times of Mixed Evidence. BIOMED RESEARCH INTERNATIONAL 2015; 2015:143109. [PMID: 26301240 PMCID: PMC4537707 DOI: 10.1155/2015/143109] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/21/2015] [Revised: 05/18/2015] [Accepted: 05/28/2015] [Indexed: 12/18/2022]
Abstract
Almost forty years ago, it was first hypothesized that an increased dietary intake of omega-3 polyunsaturated fatty acids (PUFA) from fish fat could exert protective effects against several pathologies. Decades of intense preclinical investigation have supported this hypothesis in a variety of model systems. Several clinical cardiovascular studies demonstrated the beneficial health effects of omega-3 PUFA, leading medical institutions worldwide to publish recommendations for their increased intake. However, particularly in recent years, contradictory results have been obtained in human studies focusing on cardiovascular disease and the clinical evidence in other diseases, particularly chronic inflammatory and neoplastic diseases, was never established to a degree that led to clear approval of treatment with omega-3 PUFA. Recent data not in line with the previous findings have sparked a debate on the health efficacy of omega-3 PUFA and the usefulness of increasing their intake for the prevention of a number of pathologies. In this review, we aim to examine the controversies on the possible use of these fatty acids as preventive/curative tools against the development of cardiovascular, metabolic, and inflammatory diseases, as well as several kinds of cancer.
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N-3 polyunsaturated fatty acids intake and risk of colorectal cancer: meta-analysis of prospective studies. Cancer Causes Control 2014; 26:133-41. [PMID: 25416450 DOI: 10.1007/s10552-014-0492-1] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2014] [Accepted: 11/04/2014] [Indexed: 12/14/2022]
Abstract
BACKGROUND Growing body of laboratory evidence supports the beneficial effects of n-3 polyunsaturated fatty acids (PUFAs) on colorectal cancer (CRC) prevention. Epidemiologic studies investigating the relationship between n-3 PUFAs intake and risk of CRC, however, have been inconsistent. We aimed to clarify the relation by conducting a meta-analysis of prospective studies. METHODS Eligible studies were identified by searching PubMed database and by carefully reviewing bibliographies of retrieved publications. Summary relative risks (RRs) with their 95 % confidence intervals (CIs) were computed with a random-effects model. Subgroup, meta-regression, and dose-response analyses were performed to explore potential sources of heterogeneity. RESULTS A total of 14 prospective studies involving 8,775 cancer cases were included in the final analysis. Overall, total n-3 or marine PUFAs intake was not associated with risk of CRC (RR 0.99 and 1.00). However, there was a trend toward reduced risk of proximal colon cancer (total n-3 PUFAs: RR 0.83, 95 % CI 0.66-1.05; marine PUFAs: RR 0.81, 95 % CI 0.59-1.10) and a significant increased risk of distal colon cancer (total n-3 PUFAs: RR 1.26, 95 % CI 1.06-1.50; marine PUFAs: RR 1.38, 95 % CI 1.11-1.71). Furthermore, marine PUFAs intake accessed longer before diagnosis was associated 21 % reduced risk of CRC (RR 0.79, 95 % CI 0.63-1.00). CONCLUSION Overall, this meta-analysis finds no relation between n-3 PUFAs intake and risk of CRC. The observed subsite heterogeneity within colon cancer and the possible effect modification by latency time merit further studies.
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31
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Yang B, Wang FL, Ren XL, Li D. Biospecimen long-chain N-3 PUFA and risk of colorectal cancer: a meta-analysis of data from 60,627 individuals. PLoS One 2014; 9:e110574. [PMID: 25375637 PMCID: PMC4222788 DOI: 10.1371/journal.pone.0110574] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2014] [Accepted: 09/15/2014] [Indexed: 11/27/2022] Open
Abstract
Background Several prospective cohort and case-control studies reported the inconsistent association between biospecimen composition of C20 and C22 long-chain (LC) n-3 polyunsaturated fatty acid (PUFA) and colorectal cancer (CRC) risk. The aim of the present study was to investigate the association of biospecimen LC n-3 PUFA with CRC risk based on prospective cohort and case-control studies. Methods and Results Cochrane Library, PubMed, and EMBASE database were searched up to February 2014 for eligible studies. Risk ratios (RRs) or odds ratios (ORs) from prospective and case-control studies were combined using a random-effects model in the highest vs. lowest categorical analysis. Nonlinear dose-response relationships were assessed using restricted cubic spline regression models. Difference in tissue composition of LC n-3 PUFA between cases and noncases was analyzed as standardized mean difference (SMD). Three prospective cohort studies and 8 case-control studies were included in the present study, comprising 60,627 participants (1,499 CRC cases and 59,128 noncases). Higher biospecimen LC n-3 PUFA was significantly associated with a lower risk of CRC in case-control (pooled OR: 0.76; 95% CI: 0.59, 0.97; I2 = 10.00%) and prospective cohort studies (pooled RR: 0.70; 95% CI: 0.55, 0.88; I2 = 0.00%), respectively. A significant dose-response association was found of biospecimen C20:5n-3 (P for nonlinearity = 0.02) and C22:6n-3 (P for trend = 0.01) with CRC risk, respectively. Subjects without CRC have significantly higher biospecimen compositions of C20:5n-3 (SMD: 0.27; 95%: 0.13, 0.41), C22:6n-3 (SMD: 0.23; 95%: 0.11, 0.34) and total LC n-3 PUFA (SMD: 0.22; 95% CI: 0.07, 0.37) compared with those with CRC. Conclusions The present evidence suggests human tissue compositions of LC n-3 PUFA may be an independent predictive factor for CRC risk, especially C20:5n-3 and C22:6n-3. This needs to be confirmed with more large-scale prospective cohort studies.
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Affiliation(s)
- Bo Yang
- Department of Food Science and Nutrition, Zhejiang University, Hangzhou, China; Department of Preventive Medicine, Wenzhou Medical University, Wenzhou, China
| | - Feng-Lei Wang
- Department of Food Science and Nutrition, Zhejiang University, Hangzhou, China
| | - Xiao-Li Ren
- Medical Laboratory Animal Center, Wenzhou Medical University, Wenzhou, China
| | - Duo Li
- Department of Food Science and Nutrition, Zhejiang University, Hangzhou, China
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Wang W, Zhu J, Lyu F, Panigrahy D, Ferrara KW, Hammock B, Zhang G. ω-3 polyunsaturated fatty acids-derived lipid metabolites on angiogenesis, inflammation and cancer. Prostaglandins Other Lipid Mediat 2014; 113-115:13-20. [PMID: 25019221 DOI: 10.1016/j.prostaglandins.2014.07.002] [Citation(s) in RCA: 105] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2014] [Revised: 06/19/2014] [Accepted: 07/03/2014] [Indexed: 12/29/2022]
Abstract
Epidemiological and pre-clinical studies support the anti-tumor effects of ω-3 PUFAs; however, the results from human trials are mixed, making it difficult to provide dietary guidelines or recommendations of ω-3 PUFAs for disease prevention or treatment. Understanding the molecular mechanisms by which ω-3 PUFAs inhibit cancer could lead to better nutritional paradigms and human trials to clarify their health effects. The ω-3 PUFAs exert their biological activities mainly through the formation of bioactive lipid metabolites. Here we discuss the biology of cyclooxygenase, lipoxygenase and cytochrome P450 enzymes-derived ω-3-series lipid metabolites on angiogenesis, inflammation and cancer.
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Affiliation(s)
- Weicang Wang
- Department of Food Science, University of Massachusetts-Amherst, Amherst, MA 01003, United States
| | - Julia Zhu
- Department of Food Science, University of Massachusetts-Amherst, Amherst, MA 01003, United States
| | - Fei Lyu
- Department of Food Science, University of Massachusetts-Amherst, Amherst, MA 01003, United States
| | - Dipak Panigrahy
- Center for Vascular Biology Research and Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, United States
| | - Katherine W Ferrara
- Department of Biomedical Engineering, University of California, Davis, CA 95616, United States
| | - Bruce Hammock
- Department of Entomology and Comprehensive Cancer Center, University of California, Davis, CA 95616, United States.
| | - Guodong Zhang
- Department of Food Science, University of Massachusetts-Amherst, Amherst, MA 01003, United States.
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33
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Song M, Chan AT, Fuchs CS, Ogino S, Hu FB, Mozaffarian D, Ma J, Willett WC, Giovannucci EL, Wu K. Dietary intake of fish, ω-3 and ω-6 fatty acids and risk of colorectal cancer: A prospective study in U.S. men and women. Int J Cancer 2014; 135:2413-23. [PMID: 24706410 DOI: 10.1002/ijc.28878] [Citation(s) in RCA: 80] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2014] [Accepted: 03/12/2014] [Indexed: 01/25/2023]
Abstract
The association between fish, ω-3 and ω-6 polyunsaturated fatty acid (PUFA) intake and risk of colorectal cancer (CRC) remains inconclusive. Recent prospective studies suggest that the relationship may vary by gender, subsite and duration of follow-up. We followed 123,529 US adults (76,386 women and 47,143 men) without a history of cancer at baseline for 24 to 26 years. Fish and PUFA intake was assessed at baseline and updated every 4 years by using a validated food-frequency questionnaire. We found no overall association between fish, ω-3 and ω-6 PUFA intake and CRC risk with hazard ratio (HR) of 1.03 [95% confidence interval (CI): 0.89-1.20] comparing marine ω-3 intake of ≥ 0.30 g/d versus <0.15 g/d among women and 1.05 (95% CI: 0.85-1.30) comparing intake of ≥ 0.41 g/d versus <0.16 g/d among men. However, fish and marine ω-3 PUFA intake appeared to be positively associated with risk of distal colon cancer in both men and women and inversely with risk of rectal cancer in men. In an analysis based on a limited number of cases, marine ω-3 PUFA intake assessed 12-16 years before diagnosis tended to be inversely associated with CRC risk in men (HR: 0.76; 95% CI: 0.52-1.10). In conclusion, although no overall association between fish, ω-3 or ω-6 PUFA intake was observed with CRC risk, marine ω-3 PUFA may be differentially associated with risk of distal colon and rectal cancers and a long latency may be needed for its protection against CRC in men.
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Affiliation(s)
- Mingyang Song
- Department of Nutrition, Harvard School of Public Health, Boston, MA; Department of Epidemiology, Harvard School of Public Health, Boston, MA
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Yang P, Jiang Y, Fischer SM. Prostaglandin E3 metabolism and cancer. Cancer Lett 2014; 348:1-11. [PMID: 24657656 DOI: 10.1016/j.canlet.2014.03.010] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2014] [Revised: 03/03/2014] [Accepted: 03/07/2014] [Indexed: 01/13/2023]
Abstract
The anticancer activity of n-3 fatty acids, especially those derived from fish, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid) (DHA), has been studied for centuries. While there is a growing body of evidence that EPA and DHA may influence cancer initiation and development through targeting multiple events of tumor development, the underlying mechanisms responsible for these activities are still not fully understood. A number of studies have suggested that the anticancer activities of EPA and DHA are associated with their effects on eicosanoid metabolism by which they inhibit prostaglandin E2 (PGE2) production. In contrast to DHA, EPA can function as a substrate for cyclooxygenases (COXs) to synthesize unique 3-series prostaglandin compounds, especially PGE3. With advance technology in mass spectrometry, there is renewed interest in studying the role of PGE3 in EPA elicited anti-proliferative activity in various cancers, with some promising results. Here, we summarize the regulation of PGE3 synthesis in cancer cells and its role in EPA elicited anticancer activity. The development of PGE3 and its metabolites as potential biomarkers for future clinical evaluation of EPA and fish oil in cancer care is discussed.
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Affiliation(s)
- Peiying Yang
- Department of General Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, United States.
| | - Yan Jiang
- Department of General Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, United States
| | - Susan M Fischer
- Department of Molecular Carcinogenesis, The University of Texas, MD Anderson Cancer Center, Houston, TX, United States
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Stonik VA, Fedorov SN. Marine low molecular weight natural products as potential cancer preventive compounds. Mar Drugs 2014; 12:636-71. [PMID: 24473167 PMCID: PMC3944507 DOI: 10.3390/md12020636] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2013] [Revised: 01/14/2014] [Accepted: 01/15/2014] [Indexed: 12/17/2022] Open
Abstract
Due to taxonomic positions and special living environments, marine organisms produce secondary metabolites that possess unique structures and biological activities. This review is devoted to recently isolated and/or earlier described marine compounds with potential or established cancer preventive activities, their biological sources, molecular mechanisms of their action, and their associations with human health and nutrition. The review covers literature published in 2003–2013 years and focuses on findings of the last 2 years.
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Affiliation(s)
- Valentin A Stonik
- Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Prospect 100 let Vladivostoku, 159, Vladivostok 690950, Russia.
| | - Sergey N Fedorov
- Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Prospect 100 let Vladivostoku, 159, Vladivostok 690950, Russia.
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A randomized controlled trial of eicosapentaenoic acid and/or aspirin for colorectal adenoma prevention during colonoscopic surveillance in the NHS Bowel Cancer Screening Programme (The seAFOod Polyp Prevention Trial): study protocol for a randomized controlled trial. Trials 2013; 14:237. [PMID: 23895505 PMCID: PMC3733694 DOI: 10.1186/1745-6215-14-237] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2012] [Accepted: 07/19/2013] [Indexed: 12/15/2022] Open
Abstract
Background The naturally-occurring omega (ω)-3 polyunsaturated fatty acid (PUFA) eicosapentaenoic acid (EPA) reduces colorectal adenoma (polyp) number and size in patients with familial adenomatous polyposis. The safety profile and potential cardiovascular benefits associated with ω-3 PUFAs make EPA a strong candidate for colorectal cancer (CRC) chemoprevention, alone or in combination with aspirin, which itself has recognized anti-CRC activity. Colorectal adenoma number and size are recognized as biomarkers of future CRC risk and are established as surrogate end-points in CRC chemoprevention trials. Design The seAFOod Polyp Prevention Trial is a randomized, double-blind, placebo-controlled, 2 × 2 factorial ‘efficacy’ study, which will determine whether EPA prevents colorectal adenomas, either alone or in combination with aspirin. Participants are 55–73 year-old patients, who have been identified as ‘high risk’ (detection of ≥5 small adenomas or ≥3 adenomas with at least one being ≥10 mm in diameter) at screening colonoscopy in the English Bowel Cancer Screening Programme (BCSP). Exclusion criteria include the need for more than one repeat endoscopy within the three-month BCSP screening period, malignant change in an adenoma, regular use of aspirin or non-aspirin non-steroidal anti-inflammatory drugs, regular use of fish oil supplements and concomitant warfarin or anti-platelet agent therapy. Patients are randomized to either EPA-free fatty acid 1 g twice daily or identical placebo AND aspirin 300 mg once daily or identical placebo, for approximately 12 months. The primary end-point is the number of participants with one or more adenomas detected at routine one-year BCSP surveillance colonoscopy. Secondary end-points include the number of adenomas (total and ‘advanced’) per patient, the location (left versus right colon) of colorectal adenomas and the number of participants re-classified as ‘intermediate risk’ for future surveillance. Exploratory end-points include levels of bioactive lipid mediators such as ω-3 PUFAs, resolvin E1 and PGE-M in plasma, urine, erythrocytes and rectal mucosa in order to gain insights into the mechanism(s) of action of EPA and aspirin, alone and in combination, as well as to discover predictive biomarkers of chemopreventive efficacy. The recruitment target is 904 patients. Trial Registration Current Controlled Trials ISRCTN05926847
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Abstract
Lipid mediators are produced from the oxidation of polyunsaturated fatty acids through enzymatic and free radical-mediated reactions. When subject to oxygenation via cyclooxygenases, lipoxygenases, and cytochrome P450 monooxygenases, polyunsaturated fatty acids give rise to an array of metabolites including eicosanoids, docosanoids, and octadecanoids. These potent bioactive lipids are involved in many biochemical and signaling pathways, with inflammation being of particular importance. Moreover, because they are produced by more than one pathway and substrate, and are present in a variety of biological milieus, their analysis is not always possible with conventional assays. Liquid chromatography coupled to electrospray mass spectrometry offers a versatile and sensitive approach for the analysis of bioactive lipids, allowing specific and accurate quantitation of multiple species present in the same sample. Here we explain the principles of this approach to mediator lipidomics and present detailed protocols for the assay of enzymatically produced oxygenated metabolites of polyunsaturated fatty acids that can be tailored to answer biological questions or facilitate assessment of nutritional and pharmacological interventions.
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Cottet V, Collin M, Gross AS, Boutron-Ruault MC, Morois S, Clavel-Chapelon F, Chajès V. Erythrocyte Membrane Phospholipid Fatty Acid Concentrations and Risk of Colorectal Adenomas: A Case–Control Nested in the French E3N-EPIC Cohort Study. Cancer Epidemiol Biomarkers Prev 2013; 22:1417-27. [DOI: 10.1158/1055-9965.epi-13-0168] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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Fatty acids in habitual diet, plasma phospholipids, and tumour and normal colonic biopsies in young colorectal cancer patients. JOURNAL OF ONCOLOGY 2012; 2012:254801. [PMID: 23319946 PMCID: PMC3540828 DOI: 10.1155/2012/254801] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/12/2012] [Accepted: 11/27/2012] [Indexed: 12/13/2022]
Abstract
Fatty acid metabolism is altered in colorectal cancer (CRC). We aimed to investigate incorporation of dietary n-6 and n-3 polyunsaturated fatty acids (PUFAs) into plasma phospholipids (PLs), tumour tissue, and normal mucosa in young CRC patients. We also aimed to study differences in PUFA composition between tumour and normal mucosa, and PUFA status associated with cancer stage. Sixty-five CRC patients younger than 55 years were included in a multicenter study. We assessed dietary fatty acid composition by food-frequency questionnaire. Fatty acid composition in plasma PL (n = 65) and tumour and normal colonic biopsies (n = 32) were analysed by gas chromatography. We observed a significant correlation for docosahexaenoic acid (DHA) between dietary intake and concentration in plasma PL (weight%) (r = 0.42; P = 0.001), but not for any n-6 PUFA. Tissue concentrations of arachidonic acid, eicosapentaenoic acid, and DHA (weight%) were 1.7–2.5 times higher in tumour than normal mucosa (P ≤ 0.001). Concentrations of n-3 and n-6 PUFA in plasma PL and tissues were not related to Duke's stage, although patients with more severe cancer stage reported higher intake of n-3 PUFA. In conclusion, we found accumulation of the long-chained n-3 and n-6 PUFA in tumour tissue in young CRC patients.
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Printz C. Women who eat fish have fewer colon polyps. Cancer 2012. [DOI: 10.1002/cncr.27767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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