Dietary Cancer Risk Research Articles

Abstract 2212: Global cancers attributable to modifiable risk factors: Dietary factors of animal origin

Abstract Cancer is the leading cause of death worldwide. Modifiable risk factors including diet have been linked to a wide range of malignancies. We estimated the global cancer population-attributable fraction (PAF) to established and suspected dietary cancer risk factors according to the Human Development Index (HDI).Diet-cancer associations were selected from WCRF, GBD and IARC report. Dietary factors of animal origin include red meat, processed meat, fish and dairy products; cancers include nasopharynx, esophageal, stomach, colorectal, pancreatic, lung, prostate, breast cancer. Gender-specific PAF were calculated based on 1) the total and gender-specific 2022 country-specific population from World Bank; 2) the country-specific average daily dietary factors intake (g/day) for 2000-2005 from the Global Dietary Database; 3) relative risks from the meta-analyses and WCRF reports; 4) country-specific 2020 cancer incidence from WHO. Estimates were also stratified by Human Development Index (HDI).Table 1 provides the results. The PAF for red meat and processed meat was higher in high HDI countries, while that for low dairy product intake was higher in low HDI countries. According to results, changes in selected dietary factors can prevent cancer-related incidence, particularly depending on where development status of countries and access to the source of their intake. Table1: Population attributable fractions for incidence of cancer in 2020 by gender. Dietary factors and Related Cancers Relative risk (g/day) AF (N. global) – Both gender AF (N. global)- Female AF (N. global)- Male Red meat Nasopharynx(L) 1.35(100) 0.103(13750.2) 0.102(3734.9) 0.104(10015.3) Colorectal (S) 1.12(100) 0.040(78714.5) 0.040(33981.2) 0.041(44733.2) Pancreatic (L) 1.11(100) 0.037(27420.3) 0.036(8479.8) 0.037(18940.4) Lung (L) 1.22(100) 0.070(155986.9) 0.069(52442.6) 0.070(103544.4) Prostate(L) 1.04(100) 0.014(20665.6) - 0.014(20665.6) Effect on total cancers * 0.016(296537.5) 0.011(98638.5) 0.021 (197898.9) Processed meat Nasopharynx(L) 1.46(30) 0.164(22194.6) 0.154(5637.4) 0.173(16557.1) Esophagus(L) 1.3(100) 0.036(22654.9) 0.034(6345.8) 0.038(16309.2) Stomach(L) 1.21(50) 0.052(60325.8) 0.049(18161.7) 0.055(42164) Colorectal (S) 1.18(100) 0.023(45460.9) 0.021(18522.8) 0.024(26938.1) Pancreatic(L) 1.17(50) 0.043(21900.2) 0.040(9414.4) 0.046(12485.8) Lung (L) 1.14(50) 0.036(82762.9) 0.034(26023.9) 0.038(56739) Effect on total cancers * 0.014(255299.3) 0.010(84106) 0.018(171193.2) Dairy products Colorectal(S) 0.87(400) 0.092(180063.4) 0.091(77598.8) 0.093(102464.6) Breast (L) 0.95(200) 0.068(151960.9) 0.068(151960.9) - Prostate (L) 1.07(400) 0.016(24224.3) - 0.016(24224.3) Effect on total cancers * 0.019(356248.6) 0.026(229559.7) 0.013(126688.9) Fish Colorectal (L) 0.89(100) 0.022(44882.9) 0.022(18705.9) 0.024(26177) Effect on total cancers * 0.002(44882.9) 0.002(18705.9 0.003(26177) Mean (g/day) of global intake Processed meat (B=14.2/M=15.1/F=13.3), red meat (B=36.5/M=36.9/F=36), fish(B=23/M=22.1/F=23.8), dairy products(B=77/M=74.9/F=79)S=strong evidenceL=limited evidence*All cancers excl. non-melanoma skin cancer (B= 18094716/F=8751759/M=9342957) 1 Citation Format: Monireh Sadat Seyyedsalehi, Edward Giovannucci, Paolo Boffetta. Global cancers attributable to modifiable risk factors: Dietary factors of animal origin [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2212.

Translational and transdisciplinary research in energy balance and cancer: past is prologue.

Obesity, defined as a body mass index ≥ 30 kg/m2, is associated with an increased incidence of 13 cancers and increased mortality of 14 cancers (1,2). Obesity is strongly linked to poor diet and physical inactivity, which are also independent risk factors for cancer incidence and mortality (3-5). Estimates suggest that by 2030 obesity will overtake tobacco as the most common preventable risk factor for the development of cancer. Today, approximately 40% of US adults have a body mass index > 30 kg/m2, with rates significantly higher in Black and Hispanic individuals, especially women (6). Rising rates of obesity and associated factors threaten to slow advances in cancer prevention and treatment, underscoring the critical need for research on the causal role of body composition, physical activity, and diet in cancer risk and outcomes. Substantial gaps exist in our understanding of the relationship between energy balance and cancer. Much of the evidence to date has focused on breast cancer, generated from individuals of middle-to-higher socioeconomic status with early-stage malignancies (4). Research is needed to understand the role of obesity in influencing risk and outcomes of understudied obesity-associated cancers and in racial and ethnic minorities, patients undergoing active treatment or who have metastatic disease, cancer survivors with low income and who live in rural settings, as well as younger and geriatric populations. Mechanistic research is needed to elucidate associations of energy balance with the microbiome, epigenetics, immune function, immunotherapy, and cancer. Research is also needed on how to effectively implement and disseminate lifestyle interventions in oncology practice. In addition, research must focus on how to develop and assess successful multi-level intervention strategies at the individual and community levels. The National Cancer Institute Fiscal Year 2022 Annual Plan and Budget proposal featured obesity and cancer as a scientific topic and highlighted the importance of investing in training the next generation of cancer researchers (7). Transdisciplinary training is needed to prepare researchers to innovatively address these complex topics.

Monitoring residues of pesticides in food in Brazil: A multiscale analysis of the main contaminants, dietary cancer risk estimative and mechanisms associated.

Pesticides pose a risk for cancer development and progression. People are continuously exposed to such substances by several routes, including daily intake of contaminated food and water, especially in countries that are highly pesticide consumers and have very permissive legislation about pesticide contamination as Brazil. This work investigated the relationship among pesticides, food contamination, and dietary cancer risk. Analyzed two social reports from the Brazilian Government: the Program for Analysis of Residues of Pesticides in Food (PARA) and The National Program for Control of Waste and Contaminants (PNCRC). First, we characterized the main pesticide residues detected over the maximum limits allowed by legislation or those prohibited for use in food samples analyzed across the country. Based on this list, we estimated the dietary cancer risks for some of the selected pesticides. Finally, we searched for data about dietary cancer risks and carcinogenic mechanisms of each pesticide. We also provided a critical analysis concerning the pesticide scenario in Brazil, aiming to discuss the food contamination levels observed from a geographical, political, and public health perspective. Exposures to pesticides in Brazil violate a range of human rights when food and water for human consumption are contaminated.

Association Between Family/Neighborhood Cancer Risk Factors and Adolescent Dietary Behaviors: A Parent-Adolescent Dyadic Analysis.

Objective. This cross-sectional study examined associations between adolescent dietary behaviors and family/home environments with parent-adolescent dyadic analysis. Methods. Secondary data were analyzed for adolescents and their parents who participated in the 2014 Family Life, Activity, Sun, Health, and Eating (FLASHE) study. Relationships between adolescent and parent intake of convenience/fast-food, fruits/vegetables, and sugar, as well as family/community and mealtime environments, were examined using Pearson's correlations, 2-sample t tests, analysis of variance, and general linear model analyses. Results. Among this nationwide parent-adolescent dyad sample (N = 1890), a moderate relationship between parent and adolescent consumption of convenience/fast-foods (r = 0.426) and fruits/vegetables (r = 0.416) was found. Adolescent convenience/fast-foods intake differed by sex, neighborhood socioeconomic status, meals eaten with family, and meals eaten in front of the TV (P < .001 for all) as well as race/ethnicity (P = .004). Adolescent fruit/vegetable intake differed by home location (P = .029), school location (P = .032), meals eaten together with family, meals eaten in front of the TV, and body mass index category (P < .001 for all). Generalized linear models revealed multiple predictors of adolescent dietary behaviors. Conclusion. Findings suggest dynamic relationships between adolescent and parent dietary cancer risk factors and adolescent fruit/vegetable consumption disparities by multiple environmental factors. Interventions targeting adolescent-parent dyads may help reduce cancer risk associated with diet.

A Pilot Study to Assess Stool Sample Collection Methods for Gut Microbiome Research in Large Prospective Cohort Studies (FS07-01-19)

ObjectivesColonic microbiota can be modified by diet and other environmental exposures that are associated with risk of cancer and other diseases. In addition, the stool metabolome represents products formed by gut microbial utilization of foods, nutrients, and other compounds. The collection of stool samples for analyses of the microbiome and metabolome in prospective cohort studies may lead to a better understanding of diet and other factors in disease etiology.Most studies of the gut microbiome and metabolome have been small clinical studies and relied on the collection of stool samples that were quickly flash-frozen and stored with no preservative. However, this method of collection is not feasible in large epidemiologic studies in which participants would self-collect and ship samples to a central repository. Other methods may preclude metabolomic analyses or result in a limited amount of stool. MethodsWe designed a pilot study to inform stool collection procedures for participants enrolled in a nationwide prospective cohort study. In this pilot study, stool samples will be collected by 10 volunteers who will aliquot their sample into: 1) OMNIgene Gut collection kit, 2) 95% ethanol collection kit, (3) Fecal Occult Blood Test cards, and (4) a vial for fresh-frozen sample with no solution (i.e., the gold standard in this analysis). Fresh-frozen samples will be shipped overnight on dry ice to a central biorepository. The remaining samples will be: 1) shipped overnight on cold packs; 2) shipped overnight at ambient temperature; 3) shipped overnight after 4 days at ambient temperature; and 4) shipped overnight at ambient temperature, followed by 4-day incubation at 50 °C to mimic maximum shipment temperature. The reproducibility, stability, and accuracy of 16S sequencing and metabolomics in stool will be compared among the collection kits, and shipping and storage conditions. ResultsInitial results are anticipated by June 2019. ConclusionsThe findings of this pilot study will inform future stool collection among Cancer Prevention Study-3 (CPS-3) participants, which, when analyzed with food frequency questionnaire data, will broaden our understanding of the role of diet in cancer risk. Funding SourcesThe American Cancer Society funds the creation, maintenance, and updating of CPS-3.

Dietary pattern and oral cancer risk – a factor analysis study

The role of diet in cancer risk has mainly been investigated based on intake of individual food items. However, food consumption is made up of a combination of various food items. This study aims to determine the association of dietary patterns with oral cancer risk. A total of 306 matched cases and controls were recruited in this study. Data on dietary intake were obtained using food frequency questionnaire (FFQ). Factor analysis (FA) was performed to identify dietary patterns based on the intake of nine major food groups, resulting in four factors/components being retained. The odds ratio (OR) was computed for each component using conditional logistic regression. The first pattern labelled as 'modern' was loaded with processed foods and snacks, whereas the second pattern termed as 'prudent' was characterized by intake of fruits and vegetables. The third pattern labelled as 'traditional' consisted of beverages and starches, while the fourth pattern termed as 'combination' was loaded with intakes of dairy, fermented/salted and meat/by-products. A significant reduced risk was found for 'prudent' (OR 0.53, 95% CI=0.28-0.98), whereas an increased risk was found for both 'combination' (OR 2.43, 95% CI=1.33-4.45) and 'traditional' (OR 2.32, 95% CI=1.23-4.25) patterns. However, after adjusting for risk habits of tobacco smoking, alcohol consumption and betel quid chewing, only 'combination' (aOR 2.99, 95% CI=1.55-5.75) and 'traditional' (aOR 2.08, 95% CI=1.09-3.97) patterns remained significant. Consumption in the highest tertile of 'traditional' and 'combination' patterns may induce twice and thrice the risk of oral cancer, respectively.

The diet, prostate inflammation, and the development of prostate cancer.

Evidence that somatic inactivation of GSTP1, encoding the human pi-class glutathione S-transferase, may initiate prostatic carcinogenesis is reviewed along with epidemiological evidence implicating several environment and lifestyle factors, including the diet and sexually transmitted diseases, as prostate cancer risk factors. An integrated model is presented featuring GSTPI function as a 'caretaker' gene during the pathogenesis of prostate cancer, in which the early loss of GSTPI activity renders prostate cells vulnerable to genome damage associated with chronic prostatic inflammation and repeated exposure to carcinogens. The model predicts that the critical prostate carcinogens will be those that are substrates for GSTP1 detoxification and are associated with high prostate cancer risk diet and lifestyle habits.

Dietary cancer risk from conditional cancerogens (tumor promoters) in produce of livestock fed on species of spurge (Euphorbiaceae). IV. Toxicologic and pathophysiologic observations in lactating goats and their suckling kids fed on the irritant herbs Euphorbia nubica and Euphorbia helioscopia: an etiologic model for investigations on the putative risk of cancer by consumption of food p.

The feeding of lactating goats on usual green fodder, contaminated with Euphorbia helioscopia or E. nubica, results in poisoning of the dams as well as their suckling kids. General signs of toxicity were emaciation, depression, shedding of body hair, arching of back, and possible death. Post-mortem changes of dams and dead suckling kids included congestion and hemorrhage in cardiac muscle, lung, liver, and kidneys. Blood analyses of goats exposed to these contaminants showed an increased level of serum alanine amino transferase compared to control samples, indicating cellular destruction in the liver. The latter was confirmed by histopathological changes in the organ which include severe congestion, necrosis, and degenerative changes. The goats also suffered from deterioration of renal function as indicated by increased blood urea nitrogen and creatinine levels. In histopathologic inspections of kidney, severe congestion, hemorrhage in the cortex and medulla, as well as necrosis of epithelial cells of kidney tubules were noticed. Considerable degenerative changes were also observed in heart and lung. The pathophysiological appearances indicate that by feeding on the Euphorbia species mentioned above, the goats are poisoned in a way similar to the case of E. peplus reported previously. Such intoxication most likely is due to irritant and hyperplasiogenic diterpene ester (DTE) toxins, usually present in the aerial parts of Euphorbia species and well known as tumor promoters in mouse skin. After ingestion of the toxic plant parts by the goats, the DTE toxins might be metabolized and thereby partially detoxified. Yet, at least in part, they may show up in the milk of the goats, as indicated by severe poisoning of their suckling kids. As discussed previously in lactating goats fed on fodder contaminated with E. peplus, tumor promoters of the DTE type may enter the human food chain via this source of milk. Such milk may be considered a valuable etiologic model for the investigation of economic, ecologic, and public health problems raised by human diet polluted with tumor promoters, i.e., conditional (non-genotoxic) cancerogens.

Dietary cancer risk from conditional cancerogens (tumor promoters) in produce of livestock fed on species of spurge (Euphorbiaceae). V. Skin irriitant and tumor-promoting diterpene ester toxins of the tigliane and ingenane type in the herbs Euphorbia nubica and Euphorbia helioscopia contaminating fodder of livestock.

Irritant diterpene ester toxins were isolated from Euphorbia nubica and E. helioscopia, which are contaminants of the green fodder of livestock in Egypt. Fractionations of methanol extracts of aerial parts of both plants were monitored by the irritation unit on the mouse ear. Plant extracts were subjected to multiplicative distribution methods, yielding irritant hydrophilic fractions that were further purified by column chromatography. Final purification of the materials was achieved by TLC (silica gel) followed by HPLC, or by TLC alone. In this way, from E. nubica, five Euphorbia factors (Nu1-Nu5) were isolated and characterized as short-chain polyfunctional diterpene esters of tigliane-type parent alcohols. The two weak irritants Nul and Nu3 were triesters of 4-deoxy(4alpha)phorbol. Nu2 was shown to be a triester of the stereoisomeric tigliane-type parent alcohol 4-deoxyphorbol. Weak irritant Nu4 probably is a positional isomer of Nu2. Nu5 was characterized as a short-chain triester of 4,20-dideoxy-5xi-hydroxyphorbol. From E. helioscopia, six short- to medium-chain polyfunctional diterpene esters of the ingenane type, generally containing unsaturated acids were obtained, i.e., four irritant esters of ingenol (Euphorbia factors H1, H2, H5, and H6) and two esters of 20-deoxyingenol (non-irritant Euphorbia substance HS4, and irritant Euphorbia factor H8). All irritant Euphorbia factors of the tigliane and ingenane diterpene ester type described in this investigation are considered to be more or less active tumor promoters, i.e., conditional (non-genotoxic) cancerogens. The Euphorbia factors assayed exhibited moderate (H1) to low (H8) relative tumor-promoting potency in comparison to the ingenane prototype DTE tumor promoter 3-TI.

Dietary cancer risk from conditional cancerogens in produce of livestock fed on species of spurge (Euphorbiaceae). III. Milk of lactating goats fed on the skin irritant herb Euphorbia peplus is polluted by tumor promoters of the ingenane diterpene ester type.

Special procedures were developed to investigate poisonous milk of lactating goats fed experimentally on aerial parts of the herb Euphorbia peplus L. In extracts of the milk, weakly irritant in the mouse-ear assay, three diterpene ester toxins were detected by techniques of high-performance liquid chromatography. They are of the ingenane structural type: Euphorbia factor Pel (ingenol 20-acetate 3-angelate), Euphorbia factor Pe2 (20-deoxyingenol 3-angelate) and Euphorbia factor Pe4 (20-deoxyingenol-6alpha,7alpha-epoxide 3-angelate). From goats milk collected 15 days after cessation of the experimental feeding period, extracts were completely free of diterpene ester toxins. The toxins polluting the milk are identical to diterpene ester entities occurring in the aerial parts of E. peplus. Of these, Euphorbia factors Pel and Pe2 are known as promoters of tumors of mouse skin. Apart from the toxic Euphorbia factors, the non-toxic parent alcohol ingenol was also detected in the milk. It is absent in the plant, and may have been generated metabolically from a certain portion of the toxic diterpene esters picked up by the goats from their fodder. The results presented here provide, for the first time, data for a novel interpretation of the locally high incidence of esophageal cancer observed in certain areas in the Caspian littoral of Iran, associated with a greater consumption of goat's (and sheep's) milk.

Dietary cancer risk from conditional cancerogens in produce of livestock fed on species of spurge (Euphorbiaceae). II. Pathophysiological investigations in lactating goats fed on the skin irritant herb Euphorbia peplus and in their milk-raised kids.

Lactating goats were fed on aerial parts of the herb Euphorbia peplus L. admixed with their usual green fodder. During the experimental feeding period they showed symptoms of general poisoning. In necropsy the main toxic effects were seen in the heart, lung and liver. Histopathological examinations revealed that the primary toxic effects originated from degenerative changes in parenchymal and endothelial cells. Adverse symptoms in the liver and kidney were also reflected in an alteration of the levels of certain serum enzymes and of blood urea nitrogen. The milk of the goats fed on E. peplus, consumed by their young kids, caused poisoning and even death, with signs similar to those observed in the adult dams. These observations support the hypothesis that the poisoning observed in both milk-raised kids and mother goats is caused by diterpene ester type toxins present in the aerial parts of the herb contaminating the dams fodder. Generally, such skin irritant and hyperplasiogenic toxins are known to be highly active tumour promoters of skin and other organ, e.g. in mice. Lactating goats--as an important source of milk around the world--in a setting similar to that described, may provide a valid experimental etiological model for investigation of food polluted by tumour-promoting diterpene ester toxins.

Dietary cancer risk conditional cancerogens in produce of livestock fed on species of spurge (Euphorbiaceae). I. Skin irritant and tumor-promoting ingenane-type diterpene esters in E. peplus, one of several herbaceous Euphorbia species contaminating fodder of livestock.

The hypothesis was proposed that there is a risk of dietary cancer from conditional cancerogens in produce of livestock polluted with irritants of the diterpene ester type, picked up by feeding on species of Euphorbiaceae (spurge). To challenge this, several herbaceous plants of the genus Euphorbia, widespread as weeds and contaminants of livestock fodder, were identified botanically and extracts of their aerial parts were tested for irritancy on the mouse ear. As compared to a standard probe of croton oil, the extracts of E. peplus, E. nubica and E. helioscopia displayed irritancy. The most active extract (that from E. peplus) was investigated by a fractionation procedure monitored by the mouse ear assay, and five molecularly uniform irritant Euphorbia factors Pe1-Pe5 were identified as diterpene ester-type toxins. Together these factors comprise at least 11 ppm in the aerial parts. They were characterized individually to carry the diterpene parent alcohols ingenol, 20-deoxyingenol, and 20-deoxyingenol-6 alpha, 7alpha-epoxide. The irritancy of the aerial plant parts was shown to be caused mainly by the Euphorbia factors Pe1 and Pe2 together. Upon chronic administration of these irritants and hyperplasiogens as principal cancerogenic risk factors in the mouse skin initiation/promotion bioassay, Pe1 and Pe2 were established as tumor promoters. These findings together support the initial hypothesis and suggest the need for further investigations to determine whether there is a consequent risk of dietary cancer.

Dietary Cancer Risk of Low-Income Women and Change with Intervention

Dietary Cancer Risk of Low-Income Women and Change with Intervention

Improvement in dietary cancer risk factors of low-income, female homemakers as a result of an intervention program

Dietary risk factors for cancer (total fat, fiber, fruits, vegetables, and vitamins A and C) were assessed among 339 female homemakers before and after a 9-lesson, nutrition-based cancer prevention program. The objective of the study was to test the effectiveness of the program in improving diet-related cancer risk factors.

Dietary cancer and cardiovascular risk factors of low-income, female homemakers in the EFNEP program

Dietary risk factors for cancer and cardiovascular disease were examined among female homemakers in the Expanded Food and Nutrition Education Program (EFNEP) in Virginia, using frequency distributions and percentages. The objective of the study was to describe the dietary intake of EFNEP homemakers as to the prevalence of certain dietary risk factors for cancer and cardiovascular disease (CVD). Dietary risk factors assessed, which are associated both with cardiovascular disease and certain cancers, were daily intakes of the following: total fat in excess of 30% of calories, saturated fat in excess of 10% of calories, cholesterol in excess of 300 milligrams (mg), dietary fiber less than 20 grams (gm), and calcium less than 600 mg (75% RDA). Other factors which were assessed as risk factors for CVD were sodium intake in excess of 2400 mg, potassium intake less than 1600 mg, and mono-unsaturated and poly-unsaturated fats less than 10% of calories for each. Other dietary cancer risk factors assessed were deficient intakes (<75% of RDA) of vitamins A, C, and E.

Pesticides and food safety

This report reviews recent developments regarding the environmental, toxicological, and regulatory issues surrounding pesticide residues in food. Factors affecting the establishment of regulatory limits are discussed. Pesticides monitored by state and federal agencies are compiled and the need for improvements in analytical techniques and enforcement procedures in governmental monitoring programs is pointed out. Specific incidents of concern related to pesticides in food including EDB in grain and grain products, aldicarb in watermelon, demeton-methyl in wine, DDT in fish, S,S,S-tributylphosphorotrithioate in chili peppers, and daminozide in apples and processed apple products are described. The National Academy of Science's study on the Environmental Protection Agency's (EPA) method for setting tolerances for pesticide residues is discussed, especially the dietary cancer risk estimates from pesticides and the inconsistencies in regulating oncogenic pesticides in raw and processed foods existing under the Delaney Clause. The EPA's Tolerance Assessment System is identified to improve the quality of the tolerance establishment process. New California laws to ensure food safety include mandated activities in identifying the toxicological data gaps for pesticides and evaluating pesticide tolerances. Already initiated, tighter regulatory activities at both the federal and the state levels are expected to improve scientific information development, regulatory decisions, and public health protection.