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Dietary factors account for a large proportion of human cancers, particularly overnutrition that results in weight gain and obesity. The evidence linking diet and cancer has been developing since the early 1900s, beginning with early laboratory studies and ecologic studies of cancer rates in different parts of the world. More modern epidemiologic methods, including case–control studies, cohort studies, and randomized controlled trials have helped define in detail the associations between specific dietary factors and cancer. Factors with strong links to an increased risk of various cancers include: overnutrition/obesity, alcohol, red meat, and salt. Factors with strong links to a decreased risk include: fruits, vegetables, fiber, vitamin D, calcium, and folate.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selective killing of cancer cells underlines its anticancer potential. However, poor tolerability and resistance underscores the need to identify cancer-selective TRAIL-sensitizing agents. Apigenin, a dietary flavonoid, sensitizes lung cancer cell lines to TRAIL. It remains unknown, however, whether apigenin sensitizes primary lung cancer cells to TRAIL and its underlying mechanisms. Here we show that apigenin reprograms alternative splicing of key TRAIL/death-inducing-signaling-complex (DISC) components: TRAIL Death Receptor 5 (DR5) and cellular-FLICE-inhibitory-protein (c-FLIP) by interacting with the RNA-binding proteins hnRNPA2 and MSI2, resulting in increased DR5 and decreased c-FLIPS protein levels, enhancing TRAIL-induced apoptosis of primary lung cancer cells. In addition, apigenin directly bound heat shock protein 70 (Hsp70), promoting TRAIL/DISC assembly and triggering apoptosis. Our findings reveal that apigenin directs alternative splicing and inhibits Hsp70 enhancing TRAIL anticancer activity. These findings underscore impactful synergies between diet and cancer treatments opening new avenues for improved cancer treatments.

Background Prospective cohort studies on diet and cancer report risk associations as hazard ratios. But hazard ratios do not inform on the number of people who need to alter their dietary behaviours for preventing cancer. The objective of this study is to estimate the number of people that need to alter their diet for preventing one additional case of female breast or colorectal cancer. Methods Based on the largest prospective studies done in the USA and in Europe, we computed the number of subjects who need to alter their diet. Results For preventing one case of breast cancer, European women should increase their fruit consumption by 100 g/day during 33 000 person-years, and US women by 60 g/day during 10 600 person-years. For vegetables, European women should increase their consumption by 160 g/day during 26 900 person-years and US women by 100 g/day during 19 000 person-years. For preventing one case of colorectal cancer, European subjects should decrease their red meat consumption by 20 g/day during 26 100 person-years, and US subjects by 30 g/day during 8170 person-years. For processed meat, European subjects should decrease their consumption by 20 g/day during 17 400 person-years, and US subjects by 10 g/day during 7940 person-years. Conclusions Large number of subjects would need to alter their intake of fruits, vegetables, red and processed meat during many years in order to prevent one additional breast or colorectal cancer.

Background The considerable differences in food consumption across countries pose major challenges to the research on diet and cancer, due to the difficulty to generalise and reproduce the dietary patterns identified in a specific population. Methods We analysed data from a multicentric case-control study on oesophageal squamous cell carcinoma (ESCC) carried out between 1992 and 2009 in three Italian areas and in the Canton of Vaud, Switzerland, which included 505 cases and 1259 hospital controls. Dietary patterns were derived applying LCA on 24 food groups, controlling for country membership, and non-alcoholic energy intake. A multiple logistic regression model was used to derive odds ratio (ORs) and corresponding 95% CIs for ESCC according to the dietary patterns identified, correcting for classification error. Results and Conclusion We identified three dietary patterns. The ‘Prudent’ pattern was distinguished by a diet rich in fruits and vegetables. The ‘Western’ pattern was characterised by low consumption of these food groups and higher intakes of sugar. The ‘Lower consumers-combination pattern’ exhibited a diet poor in most of the nutrients, preferences for fish, potatoes, meat and a few specific types of vegetables. Differences between Italy and Switzerland emerged for pattern sizes and for specific single food preferences. Compared to the ‘Prudent’ pattern, the ‘Western’ and the ‘Lower consumers-combination’ patterns were associated with an increased risk of ESCC (OR=3.04, 95% CI=2.12–4.38 and OR=2.81, 95% CI=1.65–4.76).

Purpose of review Dietary factors have been linked to cancers. This review focuses on several nutrients, which have strong evidence showing increase in cancer risks in the esophagus and stomach. Recent findings Obesity is an important risk factor in upper gastrointestinal cancers. High sugar content in food and sugary drinks are the main drivers of obesity. Proinflammatory diet is another dietary factor, which is increasingly recognized as being associated with esophageal and gastric cancer. Summary Cancer has been predicted to be the leading cause of death in this century. Cancers of the esophagus and stomach are the six and third most common cause of death worldwide. Although Helicobacter pylori infection is a known cause of gastric cancer, obesity is a leading contributor to esophageal adenocarcinoma. Epidemiological data have shown that dietary factors are associated with the two cancers. Observational, case control, animal and recent large cohort studies have identified associations between dietary factors and upper gastrointestinal cancer. Data are also emerging from studies, which look at dietary patterns, such as reduction in the Dietary Inflammatory Index, as well as adherence to a modified Mediterranean diet, and its association with the incidence of esophageal and gastric cancer.

Purpose Examine the association between circulating lipids and breast cancer outcomes in patients enrolled in the Malmö Diet and Cancer Study (MDCS). Patients and methods Circulating lipid levels were measured in blood sampled upon enrollment in the female MDCS cohort (N = 17,035). We identified all MDCS participants with incident invasive breast cancer diagnosed between 1991 and 2014. Follow-up time began at breast cancer diagnosis and continued until the first event of breast cancer recurrence, death, emigration, or 5 years of follow-up. We estimated the incidence rates of recurrence at 5 years and fit Cox regression models to compute crude and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CI) of breast cancer recurrence as well as all-cause mortality according to cohort-specific tertiles of apolipoprotein A-1 (Apo A-1) and apolipoprotein B (Apo B). Results We enrolled 850 eligible patients. During the 5 years of follow-up, 90 invasive breast cancer recurrences were diagnosed over 3807 person-years. In multivariable analyses, high baseline levels of Apo B were associated with an increased rate of recurrence (tertile 3 vs. 1, HR = 2.30 [95% CI 1.13–4.68]). However, high baseline levels of Apo B were not associated with all-cause mortality (tertile 3 vs. 1, HR = 1.23 [95% CI 0.68–2.25]). We observed no associations between levels of Apo A-1 and recurrence (tertile 3 vs. 1, HR = 1.34 [95% CI 0.70–2.58]) or all-cause mortality (tertile 3 vs. 1, HR = 1.12 [95% CI 0.61–2.05]). Conclusion High pre-diagnostic levels of Apo B were associated with an increased risk of recurrence among breast cancer patients. Circulating Apo A-1 was not associated with breast cancer outcomes.

The importance of food contaminants in the link between diet and cancer has been widely demonstrated. Therefore, different physical and chemical strategies for the control of human exposure to such dietary carcinogens has been explored; however, most of these strategies are complex, costly, and have low efficiency which limited their applications. Hence, microbiological methods have been receiving more attention. Recent in vitro and in vivo studies have indicated that lactic acid bacteria (LAB) and yeast may act as dietary carcinogen-binding agents. This review describes the promising protective role of strains belonging mainly to the

Over the past decade, the search for dietary factors on which to base cancer prevention guidelines has led to the rapid expansion of the field of dietary patterns and cancer. Multiple systematic reviews and meta-analyses have reported epidemiological associations between specific cancer types and both data-driven dietary patterns determined by empirical analyses and investigator-defined dietary indexes based on a predetermined set of dietary components. New developments, such as the use of metabolomics to identify objective biomarkers of dietary patterns and novel statistical techniques, could provide further insights into the links between diet and cancer risk. Although animal models of dietary patterns are limited, progress in this area could identify the potential mechanisms underlying the disease-specific associations observed in epidemiological studies. In this Review, we summarize the current state of the field, provide a critical appraisal of new developments and identify priority areas for future research. An underlying theme that emerges is that the effectiveness of different dietary pattern recommendations in reducing risk could depend on the type of cancer or on other risk factors such as family history, sex, age and other lifestyle factors or comorbidities as well as on metabolomic signatures or gut microbiota profiles.

This chapter reviews the Epidemiology of Nutrition, Diet, and Cancer Risk from observational data on the association between nutrients, dietary patterns, and the risks of common forms of cancer and discusses potential causal inferences and possible nutritional intervention strategies for cancer prevention and control. There are two major aspects in nutrition and cancer, identifying carcinogenic and anticarcinogenic effects from dietary patterns, components, chemicals, nutrients for reduction of cancer risk, and improvement of clinical outcomes. Following successes in identifying the causal association of tobacco smoking with lung cancer, epidemiologists in the 1960s began to seriously examine associations of diet, nutrition, and cancer risk. The Bradford-Hill criteria were established in 1965 and are the most widely referenced criteria for establishing causal inferences from epidemiological data. The identification of aflatoxin B1 from diet as a group 1 carcinogen is a typical application of causal inference using the Bradford-Hill criteria in nutritional epidemiology. These criteria were developed during an early era of epidemiology when many modern advances in genetics, molecular biology, toxicology, exposure science, and statistics had not yet occurred. Many recent scientific advances have increased the options for the exploring potential cause-and-effect relationships in diet, nutrition, and cancer risk using modern epidemiological methods combined with insights from molecular biology, precision oncology, and personalized nutrition. Epidemiological research has traditionally formed the basis for dietary guidance issued by cancer organizations and government panels. As new science is integrated into epidemiology, the recommendations made are likely to be improved and made more specific. Currently, cancer prevention guidelines advocate a diet rich in fruits, vegetables, and whole grains, suggest limiting sugary foods and beverages, red and processed meats, sodium, and alcohol, and recommend avoiding foods contaminated with carcinogens. Some dietary supplements such as vitamins, minerals, and green tea have also been examined in research studies but have not been widely recommended despite their frequent use by many healthy individuals and cancer patients. Overweight and obesity-associated metabolic abnormalities are increasing around the world that are associated with cancer risk, due to overconsumption of energy-dense, high fat, glycemic load, sugary, and salty foods. Typically, individuals following a modern diet do not meet daily recommendations for fruit, vegetable, or whole grain consumption. While there is much more to learn about personalized nutrition and precision oncology, the recommendations that have emerged from decades of epidemiological research into the connections between nutrition and cancer form a valuable store of information that can be expanded as our understanding of carcinogenesis continues to evolve with new research. Over the past decades, a number of large intervention studies using a randomized controlled trial design have attempted to obtain final proof of a nutrient-cancer causal relationship. For many reasons, some of these large trials have failed to demonstrate the benefit of nutritional intervention because of the chosen endpoints, limited dose levels, and short duration. These results were at odds with the epidemiological data which inspired them. Results of some large trials have confused the public and led to press reports questioning any relationship of nutrition to cancer. A new approach is clearly needed where epidemiology provides part of the overall evidence. In this chapter, we recommend a research strategy that can integrate information from laboratory and animal studies to lead to common sense public health recommendations that are feasible and acceptable by public.

OBJECTIVES: Monitoring psychosocial, emotional, and hedonic aspects of food behavior is important to understand cancer patients’ distress and help to reduce risks of malnutrition. However, to date, there is no specific tool to measure the impact of diet, eating behavior, and chemotherapy side effects on patients’ food-related quality of life during cancer and its treatments. The objective was to develop and validate a questionnaire that aims to assess the food-related quality of life in cancer patients undergoing chemotherapy. METHODS: Relevant items from the existing food-related quality of life assessment tools were selected to compose the present 46-item questionnaire. The validation of the questionnaire was conducted in 276 healthy volunteers and 173 cancer patients. Exploratory Factor Analysis (EFA) was performed in both groups, construct and discriminant validity, and test-retest reliability were calculated. RESULTS: The questionnaire was perceived as clear and required less than14 minutes for completion (93% complete responses) in a pre-test (n = 156). The EFA allowed the inclusion of 9 dimensions in the food-related quality of life questionnaire. Common patterns between patients and healthy volunteers (factor loadings ≥ 0.4 in both groups) were used to calculate scores by dimension. Scores in the dimensions of adapting diet and sensorial discomfort (taste/odor) were higher in cancer patients, whilst scores in the dimension of discomfort in satiety were higher in healthy volunteers. Among patients with cancer, the total scores in sensorial discomfort, digestive discomfort, and discomfort in satiety were higher under chemotherapy than no treatment. Reproducibility after one week was in increasing order; digestive discomfort 0.6, adapting diet 0.61, products’ quality 0.67, cooking 0.75, healthy diet 0.76, eating and pleasure 0.80, discomfort in satiety 0.82, and sensorial discomfort 0.85. CONCLUSIONS: This 46-item questionnaire can discriminate cancer patients versus healthy volunteers, and patients receiving vs those not receiving chemotherapy. A good to very good reproducibility was found for the most important factors of food-related quality of life of patients with cancer, i.e, eating and pleasure, sensorial discomfort, and discomfort in satiety. FUNDING SOURCES: This study is funded by La Région Auvergne Rhône-Aples and La Métropôle de Lyon.

OBJECTIVES: To systematically review the published evidence on nutritional risk screening instruments, nutritional assessment and functional capacity used in hospitalized cancer patients and possible associations with unfavorable clinical outcomes. METHODS: A systematic search was performed in EMBASE, PubMed/MEDLINE, LiLACS and SciELO (publications from January 2010 to January 2021) databases by search terms related to “nutritional risk”, “nutritional assessment”, functional capacity” and “cancer”. RESULTS: 3753 articles were identified, and 321 duplicates were excluded. Of the 3432 articles analyzed by title/abstract, 109 were selected for full reading and 28 studies meeting the inclusion criteria. The agreement analysis between the researchers generated a Kappa of 0.813. The evaluated studies included comparison of tools: 1) nutritional screening, 2) nutritional screening based on laboratory parameters, 3) nutritional assessment, 4) nutritional diagnosis and, 5) functional capacity. The higher nutritional risk, worst nutritional status and low functional capacity assessed by the Nutritional Risk Screening 2002 (NRS- 2002), Patient-Generated Subjective Global Assessment (PG-SGA); Subjective Global Assessment (SGA) and lower handgrip strength, respectively, were associated with longer of hospital stay. The worst nutritional status, identified by the SGA scores, Malnutrition Universal Screening Tool (MUST) and Nutritional Risk Index (NRI) were significant predictors of postoperative mortality. CONCLUSIONS: The studies included in this systematic review showed that higher nutritional risk, worse nutritional status and low functional capacity are associated with unfavorable outcomes such as longer hospital stay and mortality. The combination of the tools can be recommended for a complete assessment of the nutritional status of hospitalized cancer patients. FUNDING SOURCES: Fundo de Incentivo à Pesquisa (FIPE) do Hospital de Clínicas de Porto Alegre, Rio Grande do Sul, Brazil. (number# 2019/0708).

OBJECTIVES: Colorectal cancer (CRC) is one of the most prevalent cancer worldwide. Evidence from epidemiological studies shows that the incidence rate of CRC among elders with age ≥ 50 years is gradually decreased, whereas the rate continuously rise in adults with age

OBJECTIVES: Nearly 40% of humans have polymorphisms in genes involved in choline metabolism which makes them prone to developing choline deficiency and increased risk for liver damage and liver cancer. Choline is a source of methyl groups needed for many steps in metabolism and epigenetic regulation of gene expression. Although epigenetic aberrations are known to be induced by choline deficiency, it remains unknown how to reverse the changes and attenuate symptoms. Interestingly, certain dietary compounds such as polyphenols have been demonstrated to reverse aberrant epigenetic patterns and exert anti-cancer action. In the present study, we investigate the effects of pterostilbene (PTS) on liver cancer development in rats fed choline-deficient diet and explore mechanisms underlying these effects. METHODS: Fischer 344 rats were fed a choline-sufficient (CSAA, healthy control group), a choline-deficient (CDAA, cancer group) L-amino acid-defined diet or a CDAA diet supplemented with PTS (134 mg/kg BW/day) (n = 6 per group). At the end of 52 weeks, analyses of liver nodules and histopathological features were performed followed by genome-wide investigation of gene expression in livers using RNA sequencing. DNA methylation was assessed by pyrosequencing. RESULTS: A total of 708 genes were significantly differentially expressed in CDAA + PTS group as compared with CDAA group. Among 351 upregulated genes were Bhmt (4.5-fold), G6pc (3.1-fold), and Aldh1l1 (2.6-fold). These metabolism-related genes were significantly downregulated in CDAA vs. CSAA group and their suppression was associated with liver cancer in previous reports. Among 357 genes found to be significantly downregulated by PTS were strong oncogenes such as Mmp12 (2-fold), Myc (1.9-fold) and Mmp27 (1.8-fold). We found PTS-mediated downregulation of Mmp12, that was a top gene upregulated in CDAA vs. CSAA, coincided with 43% hypermethylation of Mmp12 promoter. CONCLUSIONS: Our findings demonstrate that PTS-mediated changes in gene expression could correspond to changes in DNA methylation of gene regulatory regions and could at least partially explain the observed attenuation of cancer development due to choline deficiency. FUNDING SOURCES: UBC VP Academic Award, CFI John. R. Evans Leaders Fund, and BC Knowledge Development Fund granted to BS.

The way cancer cells utilize nutrients to support their growth and proliferation is determined by cancer cell-intrinsic and cancer cell-extrinsic factors, including interactions with the environment. These interactions can define therapeutic vulnerabilities and impact the effectiveness of cancer therapy. Diet-mediated changes in whole-body metabolism and systemic nutrient availability can affect the environment that cancer cells are exposed to within tumours, and a better understanding of how diet modulates nutrient availability and utilization by cancer cells is needed. How diet impacts cancer outcomes is also of great interest to patients, yet clear evidence for how diet interacts with therapy and impacts tumour growth is lacking. Here we propose an experimental framework to probe the connections between diet and cancer metabolism. We examine how dietary factors may affect tumour growth by altering the access to and utilization of nutrients by cancer cells. Our growing understanding of how certain cancer types respond to various diets, how diet impacts cancer cell metabolism to mediate these responses and whether dietary interventions may constitute new therapeutic opportunities will begin to provide guidance on how best to use diet and nutrition to manage cancer in patients.

The extent to which a favorable lifestyle may lower cancer risk in subjects with a family history of cancer is unknown. We conducted a prospective study in two Swedish cohorts, the Malmo Diet and Cancer Study (MDCS; n = 25,604) and the Malmo Preventive Project (MPP; n = 16,216). The association between a favorable lifestyle (based on nonsmoking, normal weight, absence of excessive drinking, regular physical activity and healthy diet) and cancer incidence and mortality risk was assessed using Cox regression stratified by family history of cancer (all types). A favorable lifestyle was associated with a 22% (95% confidence interval [CI]: 18–26%) and 40% (95% CI: 36–44%) lower risk of cancer incidence and mortality, respectively, compared to an unfavorable lifestyle. No significant effect modification by family history was observed but there was a null association between lifestyle and cancer incidence among subjects with two or more affected first-degree relatives. The observed relative risk estimates comparing an unfavorable with a favorable lifestyle corresponded to standardized 10-year cancer incidence rates of 11.2 vs. 9.5% in the MDCS, and 4.4 vs. 3.2% in the MPP, and a reduction in 20-year cancer mortality rate from 11.7% to 7.4% in the MDCS and 6.7% to 3.9% in the MPP. Improved adherence to cancer prevention recommendations may reduce cancer incidence and mortality risk in the general population, however, further studies are needed to assess the impact of lifestyle on cancer incidence among subjects with strong familial or polygenic risk for specific cancers. (Less)

PurposeThe association between dietary acrylamide intake and estrogen receptor-positive (ER+) breast cancer risk in epidemiological studies is inconsistent. By analyzing gene-acrylamide interactions for ER+breast cancer risk, we aimed to clarify the role of acrylamide intake in ER+breast cancer etiology.MethodsThe prospective Netherlands Cohort Study on diet and cancer includes 62,573 women, aged 55-69years. At baseline, a random subcohort of 2589 women was sampled from the total cohort for a case-cohort analysis approach. Dietary acrylamide intake of subcohort members (n=1449) and ER+breast cancer cases (n=844) was assessed with a food frequency questionnaire. We genotyped single nucleotide polymorphisms (SNPs) in genes in acrylamide metabolism, sex steroid systems, oxidative stress and DNA repair. Multiplicative interaction between acrylamide intake and SNPs was assessed with Cox proportional hazards analysis, based on 20.3years of follow-up.ResultsUnexpectedly, there was a statistically non-significant inverse association between acrylamide and ER+breast cancer risk among all women but with no clear dose-response relationship, and no association among never smokers. Among the results for 57 SNPs and 2 gene deletions, rs1056827 in CYP1B1, rs2959008 and rs7173655 in CYP11A1, the GSTT1 gene deletion, and rs1052133 in hOGG1 showed a statistically significant interaction with acrylamide intake for ER+breast cancer risk.ConclusionsThis study did not provide evidence for a positive association between acrylamide intake and ER+breast cancer risk. If anything, acrylamide was associated with a decreased ER+breast cancer risk. The interaction with SNPs in CYP1B1 and CYP11A1 suggests that acrylamide may influence ER+breast cancer risk through sex hormone pathways. This study was funded by the Dutch Cancer Society (KWF), Grant number: UM 2011-5123. Janneke Hogervorst is a postdoctoral research fellow from the Research Foundation-Flanders (FWO), no. 12J9516N. The authors thank the study participants, the Netherlands Cancer Registry, the Dutch Pathology Registry, and the Biobank of the Maastricht University Medical Center. We thank Dr. Sandra Bausch as initiator of the NLCS study, together with Prof. Piet van den Brandt. We also thank Sacha van de Crommert, Jolanda Nelissen, Conny de Zwart, Ellen Dutman, Henny Brants, and Annemie Pisters for their assistance with data entry or data management, Harry van Montfort for programming assistance, and Simone van Breda, Stijn Lumeij, Kristien Lemmens, Joy Goessens, and Leonie Jonkers for technical assistance with DNA isolation and genotyping.

Background Nut consumption has been associated with reduced cancer-related mortality. However, it is unclear whether nut consumption also reduces the risk of esophageal and gastric cancer subtypes. We prospectively investigated the relationship of tree nut, peanut, and peanut butter intake with risk of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA), and gastric non-cardia adenocarcinoma (GNCA) in the Netherlands Cohort Study.Methods In 1986, 120,852 males and females, aged 55-69 years, completed a baseline questionnaire on diet and cancer risk factors. After 20.3 years of follow-up, 133 ESCC, 200 EAC, 191 GCA, and 586 GNCA cases, and 3,720 subcohort members were available for multivariable Cox regression analyses, using a case-cohort approach.Results Increased total nut consumption was significantly associated with a decreased risk of ESCC and GNCA [HRs (95% CIs) for 10 + g/day vs. nonconsumers = 0.54 (0.30-0.96) and 0.73 (0.55-0.97), respectively], but not with EAC and GCA risk. Similar trends were observed for tree nut and peanut intake, which were mostly nonsignificant. For peanut butter intake, no significant associations were found. When excluding the first four years of follow-up to reduce the possible influence of reversed causation, the relation between nut consumption and ESCC risk attenuated, but remained inverse.Conclusions Our findings suggest that increased tree nut and peanut consumption is inversely associated with GNCA risk and possibly with ESCC risk, but not with the risk of the other esophageal and gastric cancer subtypes.

Cancer arising out of diets and protective role of diet from cancers to preserve health and nutritional status is a debate in the healthcare arena. In search of perennial conflict on diet and cancer, researchers of this review emphasized conceptual and contextual details from commonly used dietary items and practices for optimum healthcare model. Twenty-four research studies were identified from 91 potentially relevant data bases and published literatures to collate an updated idea of diet and cancer. Studies were selected on, first; all emerging nutritional plans and related reports on cancer among published literature were sketchily searched. Second, “diet” and 'cancer control was also sourced from different journals, conference proceedings, and different media reports, Third, published reports from apex bodies of global importance like different professional national and international organizations were given due weightage. We have assembled diversity of opinion on prevention and control of cancer in different academic sources. Although there is no paucity of quantitative and qualitative data on diet and cancer, there is dearth of scientific and valid suggestions from scholars on this sensitive issue. In a holistic approach, we require more translational research about diet and cancer with definitive and conclusive evidences for day-to-day application in medical practice for the improvement in clinical approach of this complex debatable paradigm.

The plethora of preclinical research data inspired the scientific community and pharma sector to design and conduct the clinical trials for assessing the dietary interventions in cancer prevention, improvising the outcome of chemotherapy and reducing toxicity and many other aspects related to betterment of cancer patient’s life. Over 1000 clinical trials of diet, nutrition, dietary supplements and foods in relation to cancer are registered at clinicaltrials.gov. Unfortunately, none of the clinical effects of dietary interventions have been approved by FDA for cancer prevention. Therefore, the upcoming clinical research settings should be more focused on understanding the molecular mechanisms and mode of action of dietary interventions on tumour/cancer cell metabolism and its impact on current chemotherapy efficacy. Such endeavours may help to develop dietary modifications as adjuvant therapeutic approach for effective management of cancer.

The researches in past one decade have identified cancer stem cells (CSCs) as a major culprit of recurrence, heterogeneity, metastasis, drug and radioresistance in cancer treatment. With the increasing awareness of the significance of a dietary intervention in human health, the research is also coevolving with the molecular understanding of association between diet and cancer. Cancer stem cells are a subpopulation of cancer cells with unique characteristics of self-renewal potential, aggressive invasiveness, promoting metastasis and demonstrated resistance against chemo- and radiotherapy. The preclinical data have clearly demonstrated the anticancer effects of dietary substances against CSCs. Series of dietary ingredients inhibit the CSC-associated signalling pathways and ultimately adversely affect maintenance of CSC stemness, survival and proliferation. To integrate the anti-CSCs dietary molecules with chemotherapy drugs, there is need to establish the safety and efficacy of these molecules by performing relevant clinical trials.

The remarkable breakthrough research in molecular biology and advancements in next-generation sequencing (NGS) have significantly enriched our understandings of the epigenetic regulation of gene expression. The advancement in epigenetic research also inspired the scientific interest for investigating the influence of diet on variety of degenerative diseases including cancer. However, the molecular underpinnings underlying these effects are poorly understood. The scientific enquiry as to how dietary ingredients influence epigenetic modifications that eventually regulate health was attributed with catalytic functions of the epigenetic enzymes, which are responsible for “writing” or “erasing” the epigenetic modifications. Voluminous preclinical data suggest that dietary bioactive ingredients modulate the epigenetic landscape by inhibiting/regulating the activity of HDACs, HAT, DNMTs, acetylation/deacetylation, sumyolation, chromatin remodelling, etc. These diet-induced histone modifications regulate the conformational dynamics of chromatin structure, which ultimately leads to changes in DNA accessibility by transcription machinery leading to gene expression. Variety of dietary bioactive molecules found in several foods act as dietary modulators, which alter the epigenetic landscape against the growth and proliferation of cancer. Searching such diet origin anticancer epigenetic modulators and making a consortium of such dietary sources will lead to the formulation of anticancer epigenetic diet.

There is evidence that diet and nutrition are modifiable risk factors for several cancers, but associations may be flawed due to inherent biases. Nutritional epidemiology studies have largely relied on a single assessment of diet using food frequency questionnaires. We conduct an umbrella review of meta-analyses of observational studies to evaluate the strength and validity of the evidence for the association between food/nutrient intake and risk of developing or dying from 11 primary cancers. It is estimated that only few single food/nutrient and cancer associations are supported by strong or highly suggestive meta-analytic evidence, and future similar research is unlikely to change this evidence. Alcohol consumption is positively associated with risk of postmenopausal breast, colorectal, esophageal, head & neck and liver cancer. Consumption of dairy products, milk, calcium and wholegrains are inversely associated with colorectal cancer risk. Coffee consumption is inversely associated with risk of liver cancer and skin basal cell carcinoma., Diet and food intake have been associated with a risk of developing different types of cancer but individual nutritional epidemiology studies are prone to inherent bias. Here, the authors perform an umbrella review of meta-analyses of observational studies and show the level of evidence for associating food and nutrients to cancer risk.

Prostate cancer (PCa) is the second leading cause of cancer-related deaths in U.S. men. PCa is a slow-growing cancer; therefore, identifying dietary interventions to reduce the risk or progression of PCa could greatly impact public health. A growing body of evidence has identified several foods that may reduce the risk of PCa. Mechanistic studies have investigated individual bioactives from foods to identify their anticarcinogenic properties; however, it is also important to study the whole food. In rodent models of PCa, we have shown that consumption of whole tomato powder was more effective than lycopene alone in reducing PCa progression. In a transgenic mouse model of PCa, broccoli consumption significantly altered expression of genes involved in the epithelial-mesenchymal transition, which may be a mechanism by which broccoli intake has been associated with a reduced risk of aggressive PCa. Combinations of foods may be more protective than individual foods, but this should not be assumed, as antagonistic activity between bioactives has been suggested. We have investigated the combinations of tomato and broccoli and tomato and soy germ. Future diet and cancer research should continue to focus on whole foods and combinations of foods for better translation into recommendations for the public.

OBJECTIVES: Associations between diet and colorectal cancer (CRC) have not yet been examined in a population inhabiting the Palestinian territories, which are undergoing a nutrition transition. Understanding how diet may impact CRC risk among Palestinians is essential to developing targeted, culturally-relevant strategies that could alleviate the burden of this disease. The aim of this study was to examine how dietary fiber and fruit & vegetable (FV) intakes are associated with the risk of CRC among Palestinian adults recruited from a tertiary care facility in East Jerusalem. METHODS: This was a case-control study of 528 Palestinian men and women >18 years old who were recruited from Augusta Victoria Hospital (AVH) between 2014 and 2016. Cases included 118 patients who were treated for CRC at AVH. Controls included 410 individuals who consisted of a community-based sample of Palestinian individuals without cancer. All participants completed a survey regarding demographics, CRC-related risk factors, and a validated food screener to assess intakes of dietary fiber and FV. Multivariable logistic regression models tested associations between dietary fiber and FV intakes (categorized into quartiles) with the risk of CRC, adjusting for sex, diabetes, family history of CRC, and inflammatory bowel disease. RESULTS: After adjusting for covariates, as dietary fiber increased across quartiles of intake, the risk of CRC significantly decreased (OR for Q4 vs Q1 = 0.26, 95% CI: 0.12–0.58, p-trend = 0.0007). There was no significant association observed between FV intake and CRC risk. CONCLUSIONS: Consumption of high dietary fiber was associated with lower CRC risk in this case-control study of a Palestinian population. The development and testing of culturally-relevant dietary interventions to promote increasing dietary fiber intake among Palestinians are needed, particularly interventions targeting those at high risk for developing CRC. FUNDING SOURCES: USDA/NIFA Hatch Project 1,011,487 and a Pears Foundation Scholarship from the Robert H. Smith Faculty of Agriculture, Hebrew University of Jerusalem.

OBJECTIVES: Report my experience in treating two liver tumor patients with ketogenic diet KD protocol as monotherapy. In addition to the two patients who enrolled in this study, I also reviewed findings from 10 other patients, including 2 patients from case reports. METHODS: The ketogenic diet consists of high fat foods, foods that contain an adequate amount of protein, and a very low amount of carbohydrates. Normally, the body gets its main source of energy (sugar) from carbs. However, the ketogenic diet deprives the body of glucose, inducing a state of “ketosis.” During ketosis, the body is forced to break down stored fat instead of sugar to produce an alternative source of energy. RESULTS: The two patients who enrolled in my KD pilot study were monitored with twice daily measurements of blood glucose and ketones. Within 30 days of initiating the KD blood glucose levels declined to low-normal levels and blood ketones were elevated. Results of ultrasound images indicated that tumors has gone 1 year after KD. One patient exhibited significant clinical improvements during the study. All of these patients was treated using KD as monotherapy. No major side effects due to KD have been reported in any of these patients. They continued the ketogenic diet remaining free of disease progression. CONCLUSIONS: I conclude that: 1. KD is safe and without major side effects; 2. ketosis can be induced using customary foods; 3. treatment with KD may be effective in controlling the progression of some liver cancer cells; 4. Maybe we can manipulate our own biological system a little bit or activate something we already have in place in order to more effectively combat cancer. FUNDING SOURCES: DoTerra Science.

OBJECTIVES: Breast cancer is the most diagnosed form of cancer among American women. Worldwide, it is second only to lung cancer. Phytosterols are phytochemicals found in plant foods that have potential benefits for breast cancer. Research on phytosterols and cancer associations to date has been limited to breast cancer cell lines and animal studies, and the results have been promising. Our objective is to examine the association between breast cancer incidence and phytosterol intake in the Adventist Health Study-2, a large cohort in North America. METHODS: The present study estimated the association between phytosterol intake and breast cancer incidence in 52,734 females who were part of the Adventist Health Study 2 (AHS-2) cohort. Breast cancer cases (n = 1050) were ascertained with tumor registries from 2008 to 2014. Phytosterols content in foods was quantified by using USDA 17 and other published sources. These values were used to estimate phytosterol intake from food intake assessed by a self-administered food frequency questionnaires (FFQ). RESULTS: Hazard ratios were below the null, but statistically non-significant for β-sitosterol [HR = 0.77, 95%CI (0.44–1.36)], campesterol [HR = 0.84, 95%CI (0.46–1.55)], stigmasterol [HR = 0.76 (0.46–1.26)], and total phytosterol [HR = 0.77, 95%CI (0.43–1.40)]. In premenopausal women, HRs ranged between 0.95–1.72; in postmenopausal women, HRs were below the null, ranging between 0.67–0.83. In both premenopausal and postmenopausal women, HRs were statistically non-significant. CONCLUSIONS: The inverse association between phytosterol consumption and breast cancer incidence appears uncertain. The uncertainty possibly could be due to lack of power or measurement error. Additional epidemiological studies with a larger number of breast cancer cases, improved phytosterol intake estimates, or both are needed. FUNDING SOURCES: Unilever Research &Development, Vlaardingen, The Netherlands.

OBJECTIVES: Cancer-specific diet and exercise recommendations are not often discussed during oncology visits due to limited time and resources. eHealth [i.e., apps, activity trackers, electronic medical records (EMR)] could facilitate patient-clinician communication about health behaviors, but it is unknown how cancer survivors use eHealth and how engaged they are with digital technologies. We investigated cancer survivors’ eHealth practices and whether their engagement differs from those without a cancer history. METHODS: Cycle 1 and 2 data from the National Cancer Institute Health Information National Trends Survey 5 were used for this study. Of the 6751 adults included in our analysis, 1097 had a cancer history; the remainder served as the comparison group. We examined participants’ engagement with tablets and/or smartphone apps and the EMR. Adjusted polytomous logistic regression models were performed to estimate associations between cancer history and eHealth engagement. Descriptive results were weighted, and the jackknife replication method was used to account for the complex sampling design. Significance threshold was set at p

OBJECTIVES: Ultra-processed food (UPF) consumption is associated with excess calorie intake and weight gain. Weight gain and obesity contributes to the risk of 13 types of cancer. We aim to quantify obesity-related cancer burden associated with UPF consumption among US adults. METHODS: We used a Comparative Risk Assessment (CRA) model to estimate the number and proportion of obesity-related cancer cases associated with UPF consumption among US adults aged 20 + years in 2015. The model incorporated data and corresponding uncertainty on UPF consumption estimated from a nationally representative sample of US adults who participated in the National Health and Nutrition Examination Survey 2013–2016, effects of UPF consumption on increasing calorie intake from a randomized controlled trial, estimated weight reduction in response to calorie reduction in consideration of reduced energy expenditure, BMI-cancer relative risk estimates from meta-analyses of prospective cohort studies, and the 2015 national cancer incidence obtained from Surveillance, Epidemiology, and End Results. RESULTS: An estimated 15,200 (95% uncertainty interval [UI]: 13,900–16,400) obesity-related cancer cases newly diagnosed in 2015 among US adults were associated with high UPF consumption, accounting for 1.0% (95% UI: 0.9%–1.1%) of all new cancer cases in 2015. The top 5 cancers with the largest number of new cancer cases associated with high UPF consumption were postmenopausal breast cancer (n = 3602, accounting for 1.9% of all postmenopausal breast cancer cases), endometrial cancer (n = 3590, 6.9%), kidney cancer (n = 2530, 4.3%), liver cancer (n = 1220, 3.9%), and colorectal cancer (n = 1190, 0.9%). The proportion of new cancer cases associated with UPF consumption was higher among women (1.4% [95% UI: 0.9%–1.1%]), middle-aged population (aged 45–54 years: 1.1% [95% UI: 1.0%–1.2%]; aged 55–64 years: 1.2% [95% UI: 1.1%–1.2%]), non-Hispanic blacks (1.1% [95% UI: 1.0%–1.1%]) and Hispanics (1.1% [95% UI: 1.0%–1.1%]) compared to other age, sex, and race/ethnicity groups. CONCLUSIONS: More than 15,000 new cancer cases are estimated to be associated with UPF consumption among US adults in 2015, with middle-aged women and racial/ethnic minorities experiencing higher proportions of obesity-related cancer burden associated with high UPF consumption. FUNDING SOURCES: NIH/NIMHD.

OBJECTIVES: Metabolic acidosis promotes cancer metastasis. No prospective studies have examined the association between dietary acid load and breast cancer recurrence among breast cancer survivors, who are susceptible to metabolic acidosis. Hyperglycemia promotes cancer progression and acid formation; however, researchers have not examined whether hyperglycemia can modify the association between dietary acid load and breast cancer recurrence. METHODS: We studied 3081 early-stage breast cancer survivors enrolled in the Women's Healthy Eating and Living study who provided dietary information through 24-hour recalls at baseline and during follow-up and had measurements of hemoglobin A1c (HbA1c) at baseline. We assessed dietary acid load using two common dietary acid load scores, potential renal acid load (PRAL) score, and net endogenous acid production (NEAP) score. RESULTS: After an average of 7.3 years of follow-up, dietary acid load was positively associated with recurrence when baseline HbA1c levels were ≥5.6% (median level) and ≥5.7% (pre-diabetic cut-point). In the stratum with HbA1c ≥ 5.6%, comparing the highest to the lowest quartile of dietary acid load, the multivariable-adjusted hazard ratio was 2.15 (95%CI 1.34–3.48) for PRAL and was 2.31 (95%CI 1.42–3.74) for NEAP. No associations were observed in the stratum with HbA1c levels were

OBJECTIVES: Experimental studies suggested that antioxidants could protect against skin carcinomas. However, epidemiological studies on antioxidant supplement use in relation to basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC) risks yielded inconsistent findings, and few prospective studies have been conducted to date. We aimed to investigate intake of antioxidants supplements and risk of keratinocytes cancers (KCs). METHODS: E3N (Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale) is a prospective cohort of 98,995 French women aged 40–65 years in 1990. Intakes of antioxidants from diet were estimated via a validated food questionnaire in 1993, and antioxidant supplements use through questionnaires in 1995. We used Cox proportional hazards regression models to compute hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age and main known skin cancer risk factors. RESULTS: Over 1995–2014, 2425 BCC and 451 SCC cases were diagnosed among 63,063 women. We found positive relationships between vitamin A supplement use and KCs risk (HR = 1.37, 95% CI = 1.15–1.62), particularly with BCC (HR = 1.40, 95% CI = 1.17–1.69); and between vitamin E supplement use and risk of both BCC (HR = 1.21, 95% CI = 1.03–1.52) and SCC (HR = 1.43, 95% CI = 1.03–1.99). However, while intake of beta-carotene supplement was associated with increased SCC risk (HR = 1.59, 95% CI = 1.00–2.54), there was not associated with BCC risk, although with no heterogeneity across KC types (P(heterogeneity )= 0.21). Vitamin C supplement was also not associated with KCs. CONCLUSIONS: These findings suggest that intake of vitamin A or E supplement was associated with an increased KCs risk in women. Further studies with information on doses and duration of supplements and the ability to examine their underlying mechanisms are needed. FUNDING SOURCES: This work was supported by the Mutuelle Générale de l'Education Nationale (MGEN); the Gustave Roussy Institute; and the French League against Cancer (LNCC). Yahya Mahamat-Saleh was supported by research scholarships from the Paris Ile-de-France region and the EHESP (French School of Public Health).

OBJECTIVES: Late diagnosis, aggressive underlying biology, and limited treatment options contribute towards the exceptionally poor survival of pancreatic ductal adenocarcinoma (PDAC). Obesity promotes both incidence and progression of PDAC via chronic systemic inflammation, generation of an immunosuppressive tumor microenvironment, and promotion of tumor fibrosis. β-Hydroxy-β-Methylbutyrate (HMB) reduces cancer associated cachexia and promotes modest reductions in tumor growth in animal models of cancer. The objective of this study was to determine if HMB supplementation would alter therapeutic response to either gemcitabine or anti-PD1 immunotherapy. METHODS: C57BL/6 mice were fed either a diet induced obesity high fat diet or a matched low fat control. Following PANC02 tumor induction, animals were treated with HMB alone or in combination with gemcitabine or anti-PD1 immunotherapy. Tumor transcriptomic analysis was preformed using Affymetrix microarray, with subsequent gene set enrichment analysis. Immunohistochemistry was performed for CD3 (a T cell marker). C57BL/6 mice were fed either a diet induced obesity high fat diet or a matched low fat control. Following PANC02 tumor induction, animals were treated with HMB alone or in combination with gemcitabine or anti-PD1 immunotherapy. Tumor transcriptomic analysis was preformed using Affymetrix microarray, with subsequent gene set enrichment analysis. Immunohistochemistry was performed for CD3 (a T cell marker). RESULTS: DIO-induced immune suppression was partially reversed by HMB, with reduced tumor growth, increased T cell markers and enhanced efficacy of gemcitabine following HMB treatment in obese mice. Separately, HMB enhanced the efficacy of anti-PD1 immunotherapy. CONCLUSIONS: HMB enhanced PDAC immune surveillance, augmenting both cytotoxic chemotherapy and immunotherapy. HMB-induced suppression of obesity driven PDAC tumor growth, and promotion of immune surveillance may provide extend the therapeutic index of both chemotherapies and immunotherapies in PDAC. FUNDING SOURCES: This study was supported by a grant from the National Cancer Institute (R35 CA197627) to SDH.

OBJECTIVES: There is increasing evidence suggesting that microbiota may play a role in breast cancer disease and influence the disease severity. Several mechanisms may be involved in this relationship. Our hypothesis is that the role of microbiota in the disease may be at least partly related to its influence in gut lipid and lipoprotein metabolisms. This hypothesis was tested in an in vitro model combining MCF7 and Caco2 cells. METHODS: 32 women newly diagnosed for breast cancer, before any treatment and 28 apparently healthy women provided their stools from which bacterial DNA was extracted and amplified by qPCR, targeting 16S rRNA sequences specific to bacterial groups. Fecal waters (FW) were also obtained from these stools. Intestinal Caco-2 cells grown on filter inserts were incubated apically with 10% FW for 24 h. Then, MCF-7 cells were incubated with the whole basolateral medium for 24 h. The viability of these cells was estimated by MTT test. In parallel, LXR, apolipoproteins AIV and E gene expression was estimated by RT QPCR in CaCo2 cells and short chain fatty acids (SCFA) were quantified in FW. A logistic regression model was used to establish the Odds ratios (OR) for the disease of MCF7 viability and CaCo2 gene expression. The relationship between % bacterial groups, CaCo2 gene expression, SCFA and viability was established by regression models. RESULTS: Patients and controls differed by the MCF7 viability (1.05 [1.01–1.10], p = 0.04) and a tendency towards a difference was observed for apo AIV gene expression (0.63 [0.39–1.01], p = 0.055), (OR [5th-95th]). Viability was positively correlated with % Bifidobacterium sp. (21.18 ± 7.66, p = 0.008) and negatively correlated with valerate (−2.849 ± 1.048, p = 0.009), (ß±s.d.). These correlations were maintained in a multiple regression model. CONCLUSIONS: Microbiota may interact with intestine cell lipid metabolism and therefore influence cancer disease through gut cell secretion or permeability. FUNDING SOURCES: Ligue Contre le cancer and private funds from Integrated Center for Oncology.

OBJECTIVES: Time restricted feeding is a novel approach to intermittent fasting which includes a 6–10 hour feeding window and a 14–18 hour fasting window daily. Some forms of intermittent fasting have resulted in improvement in IGF-1 and IGFBP-3 in mice. These factors may affect cancer risk and cancer progression after diagnosis. However, effect in humans remains unknown. This exploratory analysis examined the effect of 12 weeks of 8-hour time-restricted feeding (10:00–18:00) and 8 weeks of 6-hour time-restricted feeding (12:00–18:00) versus a control in adults with obesity. METHODS: Participants with obesity (n = 24) participated in either an 8-h time restricted feeding intervention (ad libitum feeding between 10:00–6:00 pm) for 12 weeks or a 6-h time restricted feeding intervention (ad libitum feeding between 1:00–700 pm) for 8 weeks. Data for two time-restricted feeding trials were combined for this exploratory analysis and compared to a no intervention control group with obesity (n = 8). Weight loss, glucose regulatory factors, IGF-1 and IGFBP3 were measured. RESULTS: Body weight decreased significantly more in the 6-h (−2.82 ± 0.05 kg) and the 8-h (−2.77 ± 0.50 kg) groups than the controls (p

OBJECTIVES: Current studies have confirmed that the sensitivity of the ketogenic diet (KD) therapy for cancer depends on the low expression of ketolytic enzymes. However, increasing evidence showed that heterogeneity of tumor metabolism leads to inconsistent efficacies of KD therapy, which broke the illusion of the possibility of cancer treatment. Our study aims to construct colon cancer metabolism-related molecular subtyping. Furthermore, to explore the metabolic heterogeneity in diverse colon cancer cells and illuminate the mechanisms of mitochondrial metabolic reprogramming. Thus, providing a theoretical basis for clinical nutritional therapy and combined intervention measures based on metabolic molecular phenotyping. METHODS: We selected 19 genes associated with glucose and the keto-body metabolic pathway, then constructed a prognostic gene signature by LASSO and KM curve. Based on the screened metabolic molecules, we further explored the nutrition metabolic heterogeneity and illuminate our understanding of mitochondrial metabolic reprogramming under nutritional stress in vivo. RESULTS: Through the integration of patients’ transcriptomics data, we stratified colon cancer patients into three significant phenotypes with distinct glycolytic and ketolytic characteristics. We identified glycolysis + subtype with either GLUT1 or PFKFB3 overexpression, and ketolysis + subtype with either OXCT1 or ACAT1 deficiency. In general, combining glycolysis+/ketolysis-phenotype demonstrated the worst prognosis. Furthermore, we discovered the metabolic heterogeneity through western blot and energy metabolic phenotype analysis which also confirmed that these different colon cancer cells showed great significance in metabolic reprogramming under nutritional stress. CONCLUSIONS: The multi-target combination of metabolic phenotyping proved to be a foundation for individualized molecular stratified treatment which plays an essential role in predicting effectiveness of nutritional modulation therapy among colon cancer patients. It provided a theoretical basis for the clinical trial of KD therapy for patients with specific metabolic subtypes of colon cancer. FUNDING SOURCES: The National Key Research and Development Program: The key technology of palliative care and nursing for cancer patients.

OBJECTIVES: Suboptimal diet contributes to substantial health disparities among low-income and racial and ethnic minorities, but influences on cancer disparities are not well established. We quantified the health and economic burdens of cancer attributable to suboptimal diet among US adults overall and in key demographic subgroups. METHODS: Using a probabilistic cohort state transition model, we incorporated national representative demographics and dietary data, national cancer incidence and cancer survival, diet-cancer etiologic associations, and cancer-related healthcare costs to estimate new cancer cases, cancer deaths, and cancer costs attributable to suboptimal intakes of 7 dietary factors (fruits, vegetables, dairy, whole grains, processed meats, red meats, sugar sweetened beverages) among US adults aged 20 + years over their lifetime. Uncertainties in inputs were incorporated using probabilistic sensitivity analyses in 1000 simulations. RESULTS: Suboptimal intakes of these 7 dietary factors were estimated to jointly cause 1.76 (95% UI: 1.69–1.81) million new cancer cases, representing 4.6% (4.5–4.8%) of total cases of these cancers, 1.04 (1.00–1.08) million cancer death, and $215B (206–223) cancer-related healthcare costs in US adults over their lifetime. The top 3 diet-attributable cancers were colorectal (n = 824,000 new cases, 17% of the total), oral cavity and pharynx (n = 204,000, 8.4%), and endometrial cancer (n = 175,000, 5.8%). Among subgroups, diet-attributable new cancer cases per 100,000 population were 16% higher for men (805 [777–843]) than women, 20% higher for non-Hispanic blacks (939 [901–954]) than non-Hispanic white, 12% higher for below college educated (771[727–817]) than college graduates, 14% higher for lower income individuals (income-to-poverty ratio

OBJECTIVES: The potential health benefits associated with mushroom consumption, including reductions in risk of cancer have gained recent research attention. We thus conducted a systematic review and meta-analysis to assess the association between mushrooms intake and risk of cancer at any site. METHODS: We searched MEDLINE, Web of Science, and Cochrane Library to identify relevant studies on mushrooms intake and cancer published from January 1, 1966 to October 1, 2019. Observational studies with relative risks (RRs) or hazard ratios (HRs) or odds ratios (ORs) and 95% confidence intervals (CIs) of cancer risk for two or more categories of mushroom intake were eligible for the present studies. Random-effects models were used to pool study results and to assess dose-response relationships between mushroom consumption and the risk of cancer. RESULTS: There were 17 studies (6 cohort and 11 case-control studies) for a total of 20,797 cancer cases. Mushroom consumption was associated with lower risk of cancer – the pooled RR was 0.66 (95% Confidence Intervals (CI): 0.55–0.78) for the highest vs lowest mushroom intakes groups. There was substantial heterogeneity between studies (I2 = 77%; p for heterogeneity

OBJECTIVES: Breast cancer remains the leading cause of malignancy-related death in females and continues to increase in prevalence worldwide. The lack of therapies for triple-negative breast cancer (TNBC) continues to be a challenge, owing to its highly metastatic and aggressive nature. Dietary flavonoids, found in fruits and vegetables, are attracting great interest in the prevention and treatment of TNBC due to their anti-carcinogenic, anti-oxidative, and anti-inflammatory properties. The goal of our project was to evaluate the structure-activity relationship and the mechanism by which flavonoids affect TNBC tumor growth and metastasis. METHODS: We investigated the effects of structurally related flavonoids on the migratory nature of human MDA-MB 231 TNBC cells by using a wound healing migration assay. To model the effects of flavonoids in tumor heterogeneity in vivo, 3-dimensional culture organoids from TNBC derived xenograft tumors were established. Small interfering RNA (siRNA) transfection of apigenin target heterogeneous nuclear ribonucleoproteins A2 (hnRNPA2), an oncogene overexpressed in cancer cells that leads to abnormal mRNA splicing, were employed to investigate how hnRNPA2 effects alternative mRNA splicing activity. RESULTS: We observed that the natural flavonoids apigenin and kaempferol inhibited migration in a dose-response manner. Conversely, the presence of a glucoside and/or the lack of double bonds within the flavonoid structure as in the case of apigenin-7-glucoside and flavanones exhibited no significant anti-metastatic effects. Analysis of hnRNPA2 knockdown revealed key insights into the interaction of apigenin with hnRNPA2 to regulate migratory behaviors. CONCLUSIONS: These novel insights showcase dietary flavonoids as practical functional foods that can benefit clinical applications in TNBC cancer prevention and treatment of tumor metastases and growth. FUNDING SOURCES: Through grants from United States Department of Agriculture, National Science Foundation, and MSU awarded to Dr. Andrea I. Doseff, NIH-T32 Plant Biotechnology for Health and Sustainability Fellowship to Meenakshi Sudhakaran, and the REPID Program funded by National Institute of Health and directed by Dr. Elahé Crockett.

OBJECTIVES: Consumption of a Western type diet is a known risk factor for colorectal cancer. Our group previously developed the total Western diet (TWD) for rodents with energy and nutrient profiles that emulate a typical Western diet. In prior studies, consumption of the TWD in C57BL6/J mice markedly enhanced gut inflammation and colon tumorigenesis. In this study, our objective was to assess the dynamics of immune and cancer pathway gene expression during the onset and resolution of DSS-induced colitis. METHODS: Male C57BL/6 J mice were fed the standard AIN93G diet or the TWD diet for 45 days; on day 21, mice were provided 1% (w/V) DSS in the drinking water for 10 days. On days 33 and 45, the colitis disease activity index was determined. Also, days 21, 33, and 45, colon mucosa was collected (n = 8 per group) and total mRNA was isolated for gene expression analysis using the NanoString nCounter Mouse PanCancer Immune Profiling Panel, which targets 750 cancer- and immune-related genes. RESULTS: Results of these targeted gene expression analyses point to striking up-regulation of hundreds of genes associated with interferon response, inflammation, innate immunity, adaptive immunity, and chemokines and receptor pathways in mice fed TWD as compared to the standard AIN diet during active colitis. In a pattern that mirrored the persistent elevation in inflammation and mucosal injury observed in our prior longitudinal studies with TWD and DSS exposure, dysregulation of many of these genes persisted through recovery from gut injury, in addition to the stimulation of other pathways, such as B-cell activation and antigen processing. CONCLUSIONS: This study is the first to assess the dynamics of immune and cancer pathway gene expression during the onset and resolution of DSS-induced colitis and the first to employ highly multiplexed, direct digital detection NanoString technology for analysis of a colitis transcriptome in mouse colon mucosa. Our observations indicate that consumption of the TWD markedly enhanced colitis, delayed recovery from gut injury, and enhanced colon tumorigenesis likely via extensive changes in expression of immune-related genes in the colon mucosa. FUNDING SOURCES: Supported by the Hatch Capacity Project from the USDA National Institute of Food and Agriculture and the Dr. Robert and Carol Deibel Family Endowment.

OBJECTIVES: Breast cancer is the most common type of cancer in women worldwide and is therefore a field of research that has gained particular relevance. Stimulation of insulin-like factor-1 (IGF-1) would increase breast cancer risk and promote relapse. Here we present a case study of a woman with HER2-positive breast cancer that, after chemotherapy and radiotherapy, followed a Healthful Predominantly Plant-based Diet. This work aimed to investigate IGF-1 plasma levels modulation through this eating pattern. METHODS: For 210 days, diet was based on regular consumption of whole grains, fruits, vegetables, nuts and seeds, legumes, and olive oil as a source of monounsaturated fat, while reducing intake of less healthy plant foods as well as other animal foods. Blood markers including IGF-1, Glycemia, Total Cholesterol, and also Body Mass Index were assessed at baseline and after 210 days. RESULTS: At baseline IGF-1 was 21 nmol/L and decreased to 16.3 nmol/L, Glycemia was 80 mg/dL and increased to 85 mg/dL, Total Cholesterol was 155 mg/dL and increased to 161 mg/dL, and BMI was 21.7 kg/m(2) decreased to 20.6 kg/m(2), after 210 days. A decrease of 22.4% in IGF-1 and an increase of 6.3% in Glycemia were noted in plasma levels of this 49 years old woman. CONCLUSIONS: Predominantly Healthful Plant-based Diet seems to modulate IGF-1 and Glycemia plasma levels in a woman diagnosed with HER2-positive breast cancer. Future research should explore mechanistic pathways through which plant-based diets may confirm these results on IGF-1 levels and to clear whether a Predominantly Healthful Plant-Based Diet might be clinically useful in HER2-positive breast cancer. FUNDING SOURCES: No funding sources.

OBJECTIVES: The objective of this study was to determine the extent to which diets with a higher inflammatory potential, as measured by the Dietary Inflammatory Index (DII), are associated with cancer development in a cohort of rural post-menopausal women. METHODS: This study was a secondary analysis of participants of a randomized control trial evaluating the effect of vitamin D and calcium supplementation on cancer development in rural, post-menopausal women in Nebraska. From this cohort, diets were evaluated via a 2005 Block Food Frequency Questionnaire (FFQ) at baseline and four years later (Visit 9). DII scores were calculated at both time points for each participant, including an unadjusted and energy-adjusted DII score. The relationship with DII scores and cancer development were evaluated using a chi-squared test and logistic regression, controlling for pertinent confounders. The difference in DII scores at baseline and Visit 9 for participants who developed cancer and non-cancer participants was examined via a repeated measure ANOVA test. RESULTS: There were 1977 participants with baseline and Visit 9 DII scores available for analysis. There was a significant difference in DII scores between baseline and Visit 9, with a significantly larger change in DII scores in the participants who developed cancer (p = 0.0194), shifting to higher pro-inflammatory scores at Visit 9. Cancer status was not associated with baseline DII scores, nor was DII score a predictor of cancer status, when controlling for confounders. CONCLUSIONS: These findings illustrate how dietary patterns in persons diagnosed with cancer had significant changes over time, increasing inflammatory diet potential. This increase in inflammatory potential in cancer patients may impact outcomes like treatment success, overall survival, and cancer recurrence, creating a need for more research to further analyze the impact of cancer diagnoses on diet changes, and if these changes are detrimental to cancer survivor outcomes. FUNDING SOURCES: None.

According to recent estimates, over one third of the human population will be diagnosed with cancer at some point in their lifetime. While genetic factors play a large part in cancer risk, as much as 50 % of cancers may be preventable through various lifestyle modifications. Nutrition is a major modifiable risk factor, both through its impacts on obesity as well as through dietary chemical exposures that can either increase or decrease cancer risk. However, specific associations and mechanistic links between diet and cancer risk are either inconsistent or elusive. New insights regarding the reciprocal interactions between diet and the gut microbiota, the trillions of organisms that reside in our intestines, may help clarify how diet impacts cancer. The gut microbiota is largely shaped by an individual's diet and has far-reaching effects on metabolism, the immune system, and inflammation- important factors in the development and progression of various cancers. Likewise, the microbiota modifies dietary components, and consequently, exposure to metabolites that can influence cancer. This review explores some of these diet-microbiota interactions in the context of their potential impacts on cancer prevention.

Between 30% to 50% of cancer cases are estimated to be preventable through reduced exposure to tobacco, occupational carcinogens, and infectious agents, and adoption of lifelong healthy eating and a physically active lifestyle. In the past, diet and cancer prevention research has aimed to understand the effects of specific foods and nutrients on cancer-related mechanisms. More recently, there has been a shift in emphasis toward a more holistic focus on patterns of diet, reflecting the goal to understand the impact of adhering to broader public health recommendations. It is increasingly apparent from observational studies that different patterns of diet and physical activity are manifest in a metabolic state that is more, or less, conducive to the acquisition of genetic and epigenetic alterations leading to carcinogenesis. Experimental studies in cell systems, animals and humans have expanded our understanding of the many mechanisms by which specific dietary constituents may modulate inflammation and immune function, carcinogen metabolism, hormone and growth-factor regulation, DNA repair capacity, cell-cycle control, and proliferation and apoptosis. However, few mechanistic studies in animal models have evaluated diets containing the complex mixtures that make up human diets. Overall, more studies are needed across the continuum of prevention research, from basic mechanistic research on the effects of diet patterns on fundamental biologic processes to studies testing the efficacy of implementing lifestyle-directed cancer prevention strategies.

Recently, Ioannidis questioned whether nutritional epidemiology could be reconciled with good scientific principles, and suggested that the field needs radical reform. One of the reforms he advocated was more randomized trials; though what diet would be tested and how it would be measured were unspecified, how adherence would be monitored was unclear or unimportant, and the length of time vaguely stated as "lifelong". The other reform was reanalysis of shared data, which actually already exists in a large number of cohort consortia of individual pooled data. The 2018 report analysis of diet and cancer from the World Cancer Fund/American Institute of Cancer Research presents a sharply different picture of our knowledge of nutrition and cancer, which has evolved immensely in the past 3 decades. Based on current knowledge, factors related to energy balance, encompassed by body mass anthropometric measures might account for about 10-15% of the U.S. cancer burden. This 10-15% encompasses physical activity and obesogenic effects of diet. About 5% may be attributable to alcohol, and another 5% to specific dietary factors combined (e.g., red and processed meat, whole grains, fiber, calcium, fruits, and vegetables). Surrogates such as attained height and age at menarche are influenced by nutrition and are consistent risk factors for cancer, supporting the importance of early nutrition. Recent data suggest that early life dietary patterns, which may be modifiable, may be important. Though important questions remain, our understanding of nutrition and cancer over the life course is coherent and has been informed by nutritional epidemiology and other data.

Background Nutrition is important for prostate cancer (PC) survivorship care to help achieve a healthy weight, reduce treatment side effects and reduce the risk of developing other chronic diseases. We aimed to advance the understanding of the nutritional needs of men with PC and services that could be potentially implemented to address them. Methods We conducted a needs assessment of nutrition services for men with PC drawing on four perspectives; 1) patient evaluation of a nutrition education session in British Columbia (BC), 2) survey of BC health professionals, 3) an environmental scan of existing nutrition services across Canada and 4) a scoping literature review. Results Patients expressed a need for more nutrition information and a desire for additional nutrition services. More than 60% of health professionals believed there is a need for more nutrition services for men with PC, and reported the focus should be on weight management or management of PC progression. The environmental scan revealed few existing services for men with PC across Canada, most were inclusive of multiple cancers and not tailored for men with PC. Eighteen completed studies were identified in the scoping literature review. The majority provided combined diet and exercise programs with various formats of delivery such as individual, group and home-based. Overall, 78% of studies reported improvements in one or more of the following measures: dietary intake/ diet quality, body composition, self-efficacy, quality of life, fatigue, practicing health behavior goals and physical function/ exercise. Four studies assessed feasibility, adherence or satisfaction with all reporting positive findings. Conclusion Despite the high prevalence of PC in Canada, and the perceived need for more support by patients and health professionals, there are limited nutrition services for men with PC. Evidence from the literature suggests nutrition services are effective and well-accepted by men with PC. Our findings define a need for standardized nutrition services for men with PC that assess and meet long term nutritional needs. Our findings also provide insight into the type and delivery of nutrition services that may help close the gap in care for men with PC.

This issue of the Journal focuses on issues in the intersection of nutritional science and cancer prevention research. In this commentary, we provide a high-level orientation for the reader to nutrition and cancer. We begin by reviewing the burden of cancer which has necessitated public policy recommending improvements to diet for the prevention of cancer in the U.S., although this is true of many other countries as well. These policy recommendations are based on the critical review of scientific evidence linking diet and cancer. We then discuss the inconsistencies in the nutrition-cancer scientific literature and the subsequent issues Registered Dietitian Nutritionists (RDNs) face when translating this literature in the clinic. We conclude with some resources for practitioners and general guidance.

One of the main challenges for cancer patients under treatment is to prevent and tackle malnutrition. The current clinical nutrition market offers different food supplements or oral nutritional support products (mainly milkshakes or modified texture products) for cancer patients under risk of malnutrition. However, it is worth mentioning that these products do not address the pleasure of eating, since they do not meet sensory requirements, such as taste and smell alterations, nor patients' food preferences, leading to a big impact on their quality of life (QOL). Still, controversy remains regarding the specific nutritional requirements for cancer patients during the disease. Several randomized controlled clinical trials yield opposite results when using different bioactive compounds such as omega-3 fatty acids or antioxidants in order to prevent malnutrition or improve QOL. The use of 'omics' technologies in oncology, such as membrane lipidomics, as a powerful tool to provide new insights for the understanding of diet and cancer and their interacting metabolic pathways, will be discussed. The better knowledge of specific requirements (nutrients, sensory parameters and food preferences) for cancer patients provides valuable information for the food industry in the design of customized food products capable of preventing malnutrition, alleviating symptoms and improving QOL. © 2017 Society of Chemical Industry.

Background High levels of blood glucose are thought to be associated with colorectal cancer (CRC) and hyperinsulinemia, an interstage in the development of CRC. The purpose of this study was to examine associations between incident CRC and blood glucose; plasma insulin; and the homeostasis model assessment for insulin resistance (HOMA2-IR), respectively, and to determine whether these associations were dependent on sex and cancer site. Methods The Malmö Diet and Cancer cardiovascular cohort comprises 6103 individuals. During 81,781 person-years of follow-up, 145 cases of CRC were identified. The hazard ratio of measured blood glucose and plasma insulin and calculated HOMA2-IR were estimated with Cox proportional hazard regression. Results An association was found between high levels of blood glucose and risk of CRC (HR: 1.72 for the highest compared with the lowest quartile; 95% CI: 1.05, 2.84; ptrend = 0.044), and colon cancer (HR: 1.70 for the highest compared with the lowest quartile; 95% CI: 0.87, 3.33; ptrend = 0.032). In men, an association was found between blood glucose and CRC (HR: 2.80 for the highest compared with the lowest quartile; 95% CI: 1.37, 5.70; ptrend = 0.001), and colon cancer (HR: 4.48 for the highest compared with the lowest quartile; 95% CI: 1.27, 15.84; ptrend = 0.007), but this was not found in women. No associations between plasma insulin, or HOMA2-IR, and CRC, were found. Conclusion High levels of blood glucose in men are associated with risk of colon cancer. The findings contribute to facilitating to identify those most in need of prevention and screening.

The number of cancer survivors is increasing and they are often highly motivated to search for information about nutrition and about physical activity in order to try to improve their treatment outcomes, quality of life and overall survival. In the light of these concerns, the World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) as well as the American Cancer Society recommend a largely plant-based diet with limited consumption of red and processed meat, and limited consumption of alcohol, as well as the maintenance of a healthy weight throughout life and regular engagement in physical activity. There is a need for well-designed large observational and intervention studies to shed more light on the association between diet and cancer survivorship, and to suggest additional means for the secondary prevention of cancer.