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Abstract
Background:
Little is known about the etiology of pancreatic cancer. Epidemiological studies on tea consumption and pancreatic cancer risk have been inconclusive. The purpose of the present study was to investigate the association between green tea drinking and the risk of pancreatic cancer in urban Shanghai, China.
Methods:
In this population-based case-control study conducted in urban Shanghai, 908 cases of pancreatic cancer and 1067 healthy controls were recruited. Information on tea drinking, including type of tea, amount of tea consumption, temperature of tea, and the duration of regular tea drinking, were collected via interview questionnaire.
Results:
We examined the association of multiple tea drinking habits with the risk of pancreatic cancer. In women, regular green tea drinking was associated with 32% reduction of pancreatic cancer risk (OR 0.68, 95% CI 0.48-0.96), compared to those who did not drink tea regularly. Increased consumption and longer duration of tea drinking were both associated with reduced pancreatic cancer risk in women. Among regular tea drinkers, lower temperature of tea was associated with reduced risk of pancreatic cancer in both men and women, independent of amount or duration of tea drinking.
Conclusions:
Habits of green tea drinking, including regular drinking, amount of consumption, persistence of the habit, and tea temperature, may lower pancreatic cancer risk.
... However, limited epidemiologic evidence exists for the cancer of pancreas at the time of the review. To date, numerous case-control and cohort studies [9][10][11][12][13][14][15][16] have been performed to elucidate the role of green tea consumption with respect to its effect on pancreatic cancer development, with inconsistency remains. To further clarify this subject, a meta-analysis of observational studies was carried out. ...
... A dose-response analysis according to the method proposed by Greenland and Longnecker [18] and Orsini et al. [19] was also performed. For the studies [9,11] that assessed green tea consumption in terms of gram (g) of tea leaves, we rescaled tea intake to the number of cups per day by assuming 2.5 g tea leaves as approximately equivalent to one cup. For every study, the median or mean level of green tea for each category was assigned to each corresponding risk estimate. ...
... The search strategy yielded 288 citations ( Figure 1), of which 13 potentially relevant articles were retrieved and assessed in more detail. Finally, a total of 8 observational studies [9][10][11][12][13][14][15][16], including three case-control studies and five prospective studies that met our eligibility criteria were included. Agreement between reviewers was excellent (Kappa statistic = 0.79). ...
Emerging laboratory and animal studies indicate that green tea inhibits development and progression of pancreatic cancer, but evidence from epidemiologic studies appears inconsistent and inconclusive. A meta-analysis summarizing published case-control and cohort studies was performed to evaluate the association of green tea consumption with risk of pancreatic cancer. Pertinent studies were identified by a search of PubMed and EMBASE up to April 2014. A random-effects model was assigned to compute summary risk estimates. A total of three case-control studies and five prospective studies were included, comprising 2317 incident cases and 288209 subjects. Of them, three studies were from China and the reminders were conducted in Japan. Overall, neither high vs. low green consumption (odds ratio (OR) = 0.99, 95% confidence interval [CI] = 0.78-1.25), nor an increase in green tea consumption of two cups/day (OR = 0.95, 95% CI = 0.85-1.06) was associated with risk of pancreatic cancer. The null association persisted when the analysis was stratified by sex or restricted to non-smokers. In the stratification by study location, the summary OR for the studies from China and for those from Japan was 0.77 (95% CI = 0.60-0.99) and 1.21 (95% CI = 0.94-1.54), respectively (P for differences = 0.04). Cumulative epidemiologic evidence suggests that green tea consumption is not associated with pancreatic cancer.
... In recent years, several epidemiological studies have examined the effect of green tea intake on the risk of developing pancreatic cancer [73][74][75][76][77]. These studies have been largely inconclusive, as studies in China indicated a reduction in pancreatic cancer risk associated with green tea intake [73,76], while others in Japan found no association [74,75]. ...
... In recent years, several epidemiological studies have examined the effect of green tea intake on the risk of developing pancreatic cancer [73][74][75][76][77]. These studies have been largely inconclusive, as studies in China indicated a reduction in pancreatic cancer risk associated with green tea intake [73,76], while others in Japan found no association [74,75]. One major drawback to these epidemiological studies is that all the results were self-reported and therefore subject to bias. ...
Pancreatic ductal adenocarcinoma (PDAC) was the 12th and 11th most common cancer in men and women worldwide in 2012, with the highest incidence in North America and Europe and the lowest in Africa and Asia. Due to the lack of efficient early diagnosis and rapid disease progression, PDAC patients have a 5-year survival rate of just 5. Epidemiological studies suggest that smoking, obesity, type II diabetes, and pancreatitis are common risk factors for PDAC development. By contrast, high intake of fresh fruit, vegetables, and nuts rich in phytochemicals could reduce PDAC risk. This review summarizes the human clinical studies that have used berries or other natural products for chemoprevention of PDAC. Developing chemopreventive agents against PDAC would be tremendously valuable for the high-risk population and patients with premalignant lesions. Although some clinical trials of these agents have been completed, most are in early phases, and the results are not promising, which may be due to administration of the natural products at advanced stages of PDAC. Thus, further mechanistic studies using genetic animal models that recapitulate the tumor microenvironment and immunology of human PDAC would be informative for selecting an effective window for intervention with berries or other natural compounds.
... The population-based case-control study carried out in urban Shanghai, including 908 cases of PC and 1067 healthy controls, reported a 32 % reduction of PC risk (OR adj 0.68; 95 % CI 0.48-0.96; p = 0.03) in regular green tea drinking women, compared to those who did not drink tea regularly (Wang et al. 2012a). ...
... p = 0.18, respectively). These authors analyzed also the combinations HBsAg−/HBcAb+/HBsAb− and HBsAg−/ HBcAb+/HBsAb+ (considered as markers of a complete recovery from a HBV infections) and concluded that these viral antigen/antibody patterns are not associated with the risk of PC (Hassan et al. 2008;Ben et al. 2012;Wang et al. 2012a). ...
Pancreatic cancer (PC) is one of the most aggressive diseases. Only 10 % of all PC cases are thought to be due to genetic factors. Here, we analyzed the most recently published case–control association studies, meta-analyses, and cohort studies with the aim to summarize the main environmental factors that could have a role in PC. Among the most dangerous agents involved in the initiation phase, there are the inhalation of cigarette smoke, and the exposure to mutagenic nitrosamines, organ-chlorinated compounds, heavy metals, and ionizing radiations. Moreover, pancreatitis, high doses of alcohol drinking, the body microbial infections, obesity, diabetes, gallstones and/or cholecystectomy, and the accumulation of asbestos fibers seem to play a crucial role in the progression of the disease. However, some of these agents act both as initiators and promoters in pancreatic acinar cells. Protective agents include dietary flavonoids, marine omega-3, vitamin D, fruit, vegetables, and the habit of regular physical activity. The identification of the factors involved in PC initiation and progression could be of help in establishing novel therapeutic approaches by targeting the molecular signaling pathways responsive to these stimuli. Moreover, the identification of these factors could facilitate the development of strategies for an early diagnosis or measures of risk reduction for high-risk people.
... 36 In a large-scale, population-based case-control study in urban Shanghai, it was demonstrated that regular green tea consumption was associated with a reduction in the risk for pancreatic cancer in women. 37 Drinking low-temperature green tea led to reduced risk of this cancer in both men and women, suggesting that the temperature of the tea is an important factor for such an effect. 37 The results of a prospective cohort study with 100,507 individuals aged 40-69 years indicated that high green tea consumption may be positively associated with premenopausal thyroid cancer risk, but inversely associated with postmenopausal thyroid cancer risk. ...
... 37 Drinking low-temperature green tea led to reduced risk of this cancer in both men and women, suggesting that the temperature of the tea is an important factor for such an effect. 37 The results of a prospective cohort study with 100,507 individuals aged 40-69 years indicated that high green tea consumption may be positively associated with premenopausal thyroid cancer risk, but inversely associated with postmenopausal thyroid cancer risk. 38 Diabetes Several epidemiological studies have described the antidiabetic effects of green tea. ...
Noriyuki Miyoshi,1 Monira Pervin,1 Takuji Suzuki,2 Keiko Unno,3 Mamoru Isemura,1 Yoriyuki Nakamura1 1School of Food and Nutritional Sciences, University of Shizuoka, Yada, Shizuoka, Japan; 2Faculty of Education, Art and Science, Yamagata University, Yamagata, Japan; 3School of Pharmaceutical Sciences, University of Shizuoka, Yada, Shizuoka, Japan Abstract: Tea is derived from the leaves and buds of Camellia sinensis (Theaceae) plant, and is consumed worldwide. Green tea was discovered in the People's Republic of China approximately 3,000 BC. Lu Yu (733–803) published a book that describes the history of tea, the techniques, and utensils used for manufacturing, the method of preparation, and drinking of tea in the People's Republic of China. Green tea contains various components with specific health-promoting effects and is believed to exert protective effects against diseases such as cancer, obesity, diabetes, hepatitis, and neurodegenerative diseases. Of the various tea components, the polyphenol catechins have been the subject of extensive investigation. Among the catechins, (-)-epigallocatechin gallate has the strongest bioactivity in most cases. Caffeine induces alertness, decreases the sensation of fatigue, and has a diuretic effect. Theanine and -aminobutyric acid can lower the blood pressure and regulate brain function. Vitamin C exhibits antiscorbutic activity, prevents cataracts, and may boost the immune system. Majority of the scientific evidence based on cellular and animal experiments as well as a number of human epidemiological and intervention studies indicate that green tea and (-)-epigallocatechin gallate have beneficial health effects against various diseases. However, conflicting results have also been reported. Since confounding factors could affect the results, future studies should be designed to eliminate such factors for better understanding of the benefits of green tea on human health. Genetic and environmental factors such as race, sex, age, and lifestyle may also influence the results of human studies. Although care should be taken to avoid the consumption of green tea and supplements with very high catechin content, recent findings suggest that habitual drinking of green tea promotes longevity. Keywords: green tea, catechin, epigallocatechin gallate, EGCG, health promotion, epidemiology, clinical trials
... Red meat is possibly associated to an increased risk of pancreatic cancer, whereas a protective effect of vegetable, fruit and tea is suggested (Zatonski et al., 1993;Polesel et al., 2010). In China, few studies have examined the association of dietary habits with pancreatic cancer risk, and all of them carried out in Shanghai (Ji et al., 1995a;Ji et al., 1995b;Ji et al., 1997;Wang et al., 2012;Wang et al., 2013). ...
... One explanation for the contrary results is the possible impact and role of confounding factors such as geography and race (Lin et al., 2008). A recent population-based casecontrol study in urban Shanghai has drawn the similar result with our study (Wang et al., 2012). ...
Background:
Pancreatic cancer is the sixth leading cause of cancer death with an increasing trend in China. Dietary intake is believed to play an important role in pancreatic cancer carcinogenesis. The aim of this paper was to evaluate associations between some dietary factors and risk of pancreatic cancer in a multi-centre case-control study conducted in China.
Materials and methods:
Cases (n=323) were ascertained from four provincial cancer hospitals. Controls (n=323) were randomly selected from the family members of patients without pancreatic cancer in the same hospitals, 1:1 matched to cases by gender, age and study center. Data were collected with a questionnaire by personal interview. Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated using conditional logistic regression.
Results:
Tea intake (OR =0.49; 95%CI: 0.30-0.80) was associated with a half reduction in risk of pancreatic cancer. Reduced vegetable consumption (P trend: 0.04) was significant related to pancreatic cancer. Although no significant association was found for meat and fruit, ORs were all above or below the reference group. A protective effect was found for fruit (OR=1.73 for consumption of 1-2 times/week vs more than 3 times/week; 95%CI: 1.05-2.86). A high intake of meat was associated to a higher risk of pancreatic cancer (OR=0.59 for consumption of 1-2 times /week vs. more than 3 times /week; 95%CI: 0.35-0.97).
Conclusions:
The present study supports fruit consumption to reduce pancreatic cancer risk and indicates that high consumption of meat is related to an elevated risk. Direct inverse relations with tea and vegetable intake were also confirmed.
... [14] In a recent large-scale, population-based case-control study in urban Shanghai, regular green tea drinking was associated with a 32% reduction of pancreatic cancer risk (compared to those who did not drink tea regularly) in women who were mostly nonsmokers. [15] Such a beneficial effect of tea drinking, however, was not observed in men who were mostly smokers and former smokers; however, among men who never smoked, a trend of decreased risk was observed. [15] Similarly, a recent systematic review of epidemiological studies in Japan on green tea consumption and gastric cancer indicated no overall preventive effect of green tea in cohort studies; however, a small consistent risk reduction was found in women (but not in males because many men were smokers). ...
... [15] Such a beneficial effect of tea drinking, however, was not observed in men who were mostly smokers and former smokers; however, among men who never smoked, a trend of decreased risk was observed. [15] Similarly, a recent systematic review of epidemiological studies in Japan on green tea consumption and gastric cancer indicated no overall preventive effect of green tea in cohort studies; however, a small consistent risk reduction was found in women (but not in males because many men were smokers). When the results of all six studies were combined, there was a significant protective effect of tea drinking against stomach cancer in women who did not smoke cigarettes or drink alcohol. ...
Green tea ( Lǜ Chá), made from the leaves of the plant Camellia sinensis, has traditionally been used as a medicine in China for thousands of years. According to the classical work of Li Shizhen ( Lǐ Shí Zhēn) of the Ming Dynasty, "tea is cold and lowers the fire." Since fire (inflammation) causes many diseases, could tea be effective in the prevention of many diseases? The possible prevention of chronic diseases such as cancer, metabolic syndrome, obesity, diabetes, and cardiovascular diseases has been studied with contemporary scientific methods, and the results are promising. The molecular mechanisms underlining these observations will be discussed in this presentation. One of the reasons for the failure to demonstrate a disease-preventive effect of tea in some epidemiological studies is the lower quantities of tea consumption in humans. Can we increase the quantity of tea consumption to harness its health benefits without causing gastrointestinal irritation? This is a topic for further research.
... Similarly, in the Shanghai Men's Health Study, green tea drinking was found to reduce the risk of colorectal cancer among nonsmoking men but not among men in general (98). In a recent large-scale, population-based case-control study in urban Shanghai, regular green tea drinking was associated with a 32% reduction of pancreatic cancer risk (compared to those who did not drink tea regularly) in women, who were mostly nonsmokers (91). Such a beneficial effect of tea drinking, however, was not observed in men, who were mostly smokers and former smokers; among men who never smoked, a trend of decreased risk was observed (91). ...
... In a recent large-scale, population-based case-control study in urban Shanghai, regular green tea drinking was associated with a 32% reduction of pancreatic cancer risk (compared to those who did not drink tea regularly) in women, who were mostly nonsmokers (91). Such a beneficial effect of tea drinking, however, was not observed in men, who were mostly smokers and former smokers; among men who never smoked, a trend of decreased risk was observed (91). A similar smoking pattern in Japan, where women were mostly nonsmokers and more men were smokers, may explain the gender difference in the effects of tea consumption on gastric cancer. ...
Tea, made from leaves of the plant Camellia sinensis, Theaceae, has been used by humans for thousands of years, first as a medicinal herb and then as a beverage that is consumed widely. For the past 25 years, tea has been studied extensively for its beneficial health effects, including prevention of cancer, reduction of body weight, alleviation of metabolic syndrome, prevention of cardiovascular diseases, and protection against neurodegenerative diseases. Whether these effects can be produced by tea at the levels commonly consumed by humans is an open question. This review examines these topics and elucidates the common mechanisms for these beneficial health effects. It also discusses other health effects and possible side effects of tea consumption. This article provides a critical assessment of the health effects of tea consumption and suggests new directions for research in this area. Expected final online publication date for the Annual Review of Nutrition Volume 33 is July 17, 2013. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
... In this study, we found that in genetic prediction, increased tea consumption was associated with a decreased risk of pancreatic adenocarcinoma by the results of two-sample MR analysis based on genome-wide association studies data. The conclusion was consistent with the findings of case-control studies of Wang et al. and Liu et al. (34,35) Our results underscore the significance of tea consumption in the prevention of pancreatic adenocarcinoma and mediating effects of VEGF-D in this process, which provides novel insights for future investigations. Then, we selected fifteen representative targeted genes (ACADM, AZGP1, CCNE1, GAN, NAT1, NR3C2, PDK2, PRKD2, RARG, RUVBL1, SPEN, SUOX, USP19, VEGFA and VEGFB) by pharmacological analysis. ...
Tea is one of the most widely consumed beverages in the world. However, the association between tea and risk of pancreatic adenocarcinoma remains controversial. This study aimed to investigate the causal relationship between tea consumption and risk of pancreatic adenocarcinoma and to explore their mediating effects. The two-sample Mendelian randomisation (MR) analysis showed an inverse causal relationship between tea intake and pancreatic adenocarcinoma (OR: 0·111 (0·02, 0·85), P < 0·04). To examine the mediating effects, we explored the potential mechanisms by which tea intake reduces the risk of pancreatic adenocarcinoma. Based on the oral bioavailability and drug-like properties in Traditional Chinese Medicine Systems Pharmacology database, we selected the main active ingredients of tea. We screened out the fifteen representative targeted genes by Pharmmapper database, and the gene ontology enrichment analysis showed that these targeted genes were related to vascular endothelial growth factor (VEGF) pathway. The two-step MR analysis of results showed that only VEGF-D played a mediating role, with a mediation ratio of 0·230 (0·066, 0·394). In conclusion, the findings suggest that VEGF-D mediates the effect of tea intake on the risk of pancreatic adenocarcinoma.
... No deaths or obvious clinical signs decrease in body weight with higher doses change in organ weight change in hematological and blood chemistry liver dysfunction NOAEL: 2,500 mg/kg/day (J. Wang, Zhang, et al., 2012) Lipid-soluble green tea extract Rat, 0.58, 1.17, and 2.33 g/kg/day for 30 days, gavage ...
Many scientific articles proved that green tea (GT), Camellia sinensis, has a great potential to manage central nervous system, cardiovascular, and metabolic diseases and treat cancer and inflammatory disorders. However, it is important to consider that “natural” is not always “safe.” Some relevant articles reported side effects of GT, detrimental effects on health. The aim of this study is to provide a classified report about the toxicity of GT and its main constituents in acute, subacute, subchronic, and chronic states. Furthermore, it discusses on the cytotoxicity, genotoxicity, mutagenicity, carcinogenicity, and developmental toxicity of GT and its main constituents. The most important side effects have been reported hepatotoxicity and gastrointestinal disorders specially while consumed on an empty stomach. GT and its main components are not major teratogen, mutagen, or carcinogen substances. However, there is limited data in using them during pregnancy, and they should be used with caution in pregnancy, breast-feeding, and susceptible people. Because GT and its main components have a wide variety of drug interactions, consideration should be taken in coadministration of them with narrow therapeutic indexed drugs. Furthermore, they evoke selective cytotoxicity on cancerous cells that could engage them as an adjuvant substance in cancer therapy.
... In a study, it was reported that the copper content was in the range of 9.6-20.9 Lg/g in three brands of Chinese tea [27]. ...
... Drinking tea three times a week for more than six months was associated with a reduced likelihood of pancreatic cancer in women. Regardless of the amount or frequency of tea intake, men and women who frequently consume tea have a reduced likelihood of developing pancreatic cancer [48]. ...
This narrative review summarizes the principal findings of observational studies, systematic reviews, and meta-analyses on diet and dietary patterns' role in the risk of pancreatic cancer. Etiologically pancreatic cancer is multifactorial. Evidence exists of an association between nutrients, dietary patterns, and pancreatic cancer. An extensive literature search was conducted on PubMed, Cochrane, and Google Scholar. A thorough search of articles published in English till May 2023 and related to the review was performed. The relationship between all macronutrients, micronutrients, and various dietary patterns with the risk of pancreatic cancer was assessed. It is concluded that a diet high in nutrients like red and processed meat, refined sugars, saturated and monounsaturated fats, alcohol, copper, and a Western dietary pattern can increase the likelihood of pancreatic cancer. Contrary to this, a diet consisting of fruits, vegetables, appropriate quantities of vitamins and minerals, and a Mediterranean dietary pattern is associated with a decreased risk of pancreatic cancer.
... There are three major types of tea based on their processing and harvested leaf development, namely black, green, and oolong [9]. Various studies have reported different beneficial effects in reducing the risk of developing chronic diseases such as cancer, diabetes, arthritis, and cardiovascular diseases [10][11][12][13][14]. Tea leaves consist of different chemical compositions, including catechins, flavonols, oxy-aromatic acids, theaflavins, thearubigins, pigments, teagallins, alkaloids, amino acids, sugars, vitamins, dibasic acids, cations, lignans, metals, and triterpenoid saponins [15]. ...
Using biodegradable wastes represents a viable alternative to creating a sustainable economy that benefits all humans. The present study aimed to use daily used waste products, tea (TE) and eggshell (ES) wastes, to synthesize silver (AgNPs) and titanium oxide (TiO2NPs) nanoparticles, respectively. Firstly, the green-synthesized nanoparticles were characterized using an ultraviolet-visible spectrophotometer (UV-VIS), Scanning (SEM), transmission electron microscope (TEM), Dynamic light scattering (DLS), zeta potential analysis, X-ray diffraction (XRD), and Fourier transform infrared (FTIR) spectroscopy. Then, followed by their cytotoxic assessment against normal human skin fibroblast (HSF) cells using sulforhodamine B (SRB) assay, AgNPs_TE (300 and 470 nm) and TiO2NPs_ESE (320 nm) formation was confirmed using UV-vis spectra. SEM and XRD showed their crystalline shape. TEM images determined the nano-size of AgNPs_TE (25 nm) and TiO2NPs_ESE (120 nm), which appeared smaller in comparison with DLS analysis (299.8 and 742.9 nm), with zeta potentials of −20.5 mV and −12.6 mV, respectively. There was a great difference in both NPs’ sizes using TEM and DLS measurements because DLS is known to be more sensitive to larger particles due to their light scattering. FTIR detected the functional groups found in TE and ESE that were responsible for the synthesis, capping, and stabilization of the synthesized AgNPs and TiO2NPs. The SRB assay reveals the safety of TiO2NPs on normal HSF cells with an IC50 > 100, while AgNPs have a high cytotoxic effect with an IC50 = 54.99 μg/mL.
... Men who drank more tea were 37% less likely to develop pancreatic cancer. However, it is not clear from this population-based study whether green tea is solely responsible for lowering pancreatic cancer risk [43]. More studies are needed before researchers can recommend green tea for the prevention of pancreatic cancer. ...
The most consumed beverage in the world is tea after water. Till today the consumption of black tea is 70% while that of green tea is only 20%. One reason for this percentage is lack of awareness about green tea and invested research. Green tea along with caffeine which imparts characteristic taste, bitterness and stimulating effect, is also rich in a group of chemicals, called Catechin Polyphenols (Commonly known as Tannins, which contribute to bitter taste and astringency) and deliver antioxidant properties. Furthermore, green tea also comprises of amino acids such as Theanine along with alkaloids such as Adenine, Dimethylxanthine, Theobromine, Theophylline and Xanthine. Some vitamins, like vitamin A, vitamin B1, vitamin B2, vitamin B3, vitamin C and vitamin E are also found in green tea. The present review gives the study of various constituents of green tea and their impact on human health. Studies provide strong evidence that owing to antioxidant properties daily intake of green tea may be used as a preventive measure for different types of cancer and other diseases. This review gives a detailed analysis of constituents of green tea and highlighting it's potential as a natural nutraceutical. However, although much of the documented literature mentions positive effect yet much had to be explored on correlation between concentration of green tea and toxicity.
... Most meta-analyses concluded (i) that green tea consumption was not associated with PDAC risk and (ii) that high consumption was associated with slightly lower risk (41). This seemed more pronounced among Chinese populations (42,43). Abe et al. recently evaluated the available epidemiological evidence for green tea consumption and showed that whilst PDAC risk was not affected, several other cancers were associated significantly with reduced risk (44). ...
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease. The standard first-line treatment for PDAC is gemcitabine chemotherapy which, unfortunately, offers only limited chance of a lasting cure. This review further evaluates the hypothesis that the effectiveness of gemcitabine can be improved by combining it with evidence-based complementary measures. Previously, supported by clinical trial data, we suggested that a number of dietary factors and nutraceuticals can be integrated with gemcitabine therapy. Here, we evaluate a further 10 agents for which no clinical trials have (yet) been carried out but there are promising data from in vivo and/or in vitro studies including experiments involving combined treatments with gemcitabine. Two groups of complementary agents are considered: Dietary factors (resveratrol, epigallocatechin gallate, vitamin B9, capsaicin, quercetin and sulforaphane) and nutraceutical agents (artemisinin, garcinol, thymoquinone and emodin). In addition, we identified seven promising agents for which there is currently only basic (mostly in vitro) data. Finally, as a special case of combination therapy, we highlighted synergistic drug combinations involving gemcitabine with “repurposed” aspirin or metformin. We conclude overall that integrated management of PDAC currently is likely to produce the best outcome for patients and for this a wide range of complementary measures is available.
... Wang et al., 2012 [301] Case-control (908-1067) study conducted in urban Shanghai, China. ...
... Green tea is one of the most beverages with antioxidants and nutrients that have powerful effects on the body which include improving brain function [31][32][33], fat loss [34], lower risk of cancer [35,36], and many other impressive benefits [37,38]. There are many reports that green tea or its extract has protective effects on ischemia-reperfusion injury of the brain [39,40], heart [41,42], kidney [43], liver [44,45], and intestine [46]. ...
Green tea is one of the most beverages with antioxidants and nutrients. As one of the major components of green tea, (-)-epicatechin gallate (ECG) was evaluated for its antioxidative properties in the present study. Cell proliferation assay, tube formation, cell migration, apoptosis, and autophagy were performed in human brain microvascular endothelial cells (HBMVECs) after oxygen-glucose deprivation/reoxygenation (OGD/R) to investigate potential anti-ischemia/reperfusion injury properties of ECG in vitro. Markers of oxidative stress as ROS, LDH, MDA, and SOD were further assayed in our study. Data indicated that ECG could affect neovascularization and promote cell proliferation, tube formation, and cell migration while inhibiting apoptosis and autophagy through affecting VEGF, Bcl-2, BAX, LC3B, caspase 3, mTOR, and Beclin-1 expression. All the data suggested that ECG may be protective for the brain against ischemia/reperfusion injury by promoting neovascularization, alleviating apoptosis and autophagy, and promoting cell proliferation in HBMVECs of OGD/R.
... No deaths or obvious clinical signs decrease in body weight with higher doses change in organ weight change in hematological and blood chemistry liver dysfunction NOAEL: 2,500 mg/kg/day (J. Wang, Zhang, et al., 2012) Lipid-soluble green tea extract Rat, 0.58, 1.17, and 2.33 g/kg/day for 30 days, gavage ...
Many scientific articles proved that green tea (GT), Camellia sinensis, has a great potential to manage central nervous system, cardiovascular, and metabolic diseases and treat cancer and inflammatory disorders. However, it is important to consider that “natural” is not always “safe.” Some relevant articles reported side effects of GT, detrimental effects on health. The aim of this study is to provide a classified report about the toxicity of GT and its main constituents in acute, subacute, subchronic, and chronic states. Furthermore, it discusses on the cytotoxicity, genotoxicity, mutagenicity, carcinogenicity, and developmental toxicity of GT and its main constituents. The most important side effects have been reported hepatotoxicity and gastrointestinal disorders specially while consumed on an empty stomach. GT and its main components are not major teratogen, mutagen, or carcinogen substances. However, there is limited data in using them during pregnancy, and they should be used with caution in pregnancy, breast‐feeding, and susceptible people. Because GT and its main components have a wide variety of drug interactions, consideration should be taken in coadministration of them with narrow therapeutic indexed drugs. Furthermore, they evoke selective cytotoxicity on cancerous cells that could engage them as an adjuvant substance in cancer therapy.
... In case-control studies conducted in China and Japan, investigating the relationship between gastric cancer and tea consumption, a significant inverse relationship was found in four studies while an insignificant inverse relationship was observed in two studies [75]. Regular tea consumption was associated with 32% reduction of pancreatic cancer risk in both men and women, irrespective of the amount or duration of tea consumption among regular tea drinkers [76]. It has been reported in a study that consumption of black tea reduces colon cancer risk in both men and women [77]. ...
Medicinal plants are essential parts of traditional medicine due to their phytochemical constituents having pharmacological values and therapeutic properties. Black tea have thousands of various biological compounds such as flavanols (Thearubigins (TRs) and theaflavins (TFs) and catechins), amino acids (L.theanine), vitamins (A, C, K), flavonols (Quercetin, kaempferol, myricitin), lipids, proteins, volatile compounds carbohydrates, β-carotene and fluoride that illustrated many promising pharmacological effects regarded as growth promoter, cardioprotector, potent cholesterol-lowering effect, antioxidant and antimicrobial, etc inhuman. Although there is an exponential growth in molecular evidence of cholesterol-lowering and antioxidant effect in human, there is still a lack of information of the pharmacological effects of black tea. To fill this information gap, therefore, this review article underscores broadening the new insight pertaining to black tea that could be used as safe food additive. This article also illuminates the interesting role of black tea as an herbal medicine that is the future demand to get rid of synthetic health promoters in the human health practice. Moreover, this information would be useful in terms of the low-cost practice of natural medicines with no residual effects, and a natural protection of the human being. In addition, further studies at a molecular level are needed to reveal its mechanism of action particularly for the hypocholesterolemic effect of black tea to overcome the heart-related diseases, fewer side effects and being a natural safeguard of human health.
... In addition to the examples discussed above, a caseecontrol study on the effect of green tea consumption on esophageal cancer in Shanghai showed a protective effect only in women, who were mostly non-smokers, but not in men who were mostly smokers [112]. Similarly, in a large-scale, population-based caseecontrol study in urban Shanghai, regular green tea drinking was associated with a significant reduction of pancreatic cancer risk in women but not in men [113]. A systematic review of cohort studies in Japan on green tea consumption and gastric cancer also indicated a small consistent risk reduction in nonsmoking, nondrinking women, but not in the general cohort population [114]. ...
Tea, a popular beverage made from leaves of the plant Camellia sinensis, has been studied extensively in recent decades for its beneficial health effects in the prevention of obesity, metabolic syndrome, diabetes, cancer, and other diseases. Whereas these beneficial effects have been convincingly demonstrated in most laboratory studies, results from human studies have not been consistent. Some studies demonstrated that weight reduction, alleviation of metabolic syndrome and risk reduction in diabetes were only observed in individuals who consume 3-4 cups of tea (600-900 mg tea catechins) or more daily. This chapter reviews some of these studies, the possible mechanisms of actions of tea constituents, and the challenges in extrapolating laboratory studies to human situations.
... Epidemiological surveys (16,17) and in vivo studies (18)(19)(20) have confirmed that green tea and its extracts have antitumor effects, although the underlying molecular mechanisms remain unclear. A previous study observed that EGCG, the primary component of polyphenols in green tea, increased the methylation of the estrogen receptor-α (ERα) gene, which promoted ERα protein expression and improved the sensitivity of ERα-negative breast cancer cells to chemotherapeutic drugs (13). ...
The present study aimed to investigate the effect of treatment with epigallocatechin-3-gallate (EGCG) on the human esophageal cancer cell line ECa109 and elucidate the associated underlying mechanisms. ECa109 cells were cultured and treated with increasing concentrations of EGCG for various durations. Cell viability was evaluated using the MTT assay and apoptosis was detected using flow cytometry. The methylation status of the cyclin-dependent kinase inhibitor 2A (p16) gene was analyzed using the methylation-specific polymerase chain reaction (PCR). p16 mRNA and protein expression was measured using reverse transcription-quantitative PCR and western blot analysis, respectively. The results of the present study demonstrated that, following treatment with EGCG, ECa109 cell viability was significantly decreased, while the rate of apoptosis was significantly increased (P<0.01), in a dose-and time-dependent manner. Following treatment of ECa109 cells with EGCG, p16 gene demethylation, and its mRNA and protein expression, were significantly increased compared with the untreated cells (P<0.01). EGCG may induce ECa109 cell apoptosis and inhibit cell growth through p16 gene demethylation, which restores its expression.
... In a large-scale population-based cohort study in Japan, the results showed a decreased risk for pancreatic cancer when comparing the highest versus lowest intakes of coffee [16]. Besides, a population based case-control study conducted in Shanghai, China, showed a statistically significant inverse association with increased tea consumption and pancreatic cancer risk [17]. A previous meta-analysis [18] also reported an overall significant inverse association of low to moderate alcohol consumption (<3 drinks/day) and pancreatic cancer risk, compared with non-drinking. ...
A number of studies have examined the associations between dietary patterns and pancreatic cancer risk, but the findings have been inconclusive. Herein, we conducted this meta-analysis to assess the associations between dietary patterns and the risk of pancreatic cancer. MEDLINE (provided by the National Library of Medicine) and EBSCO (Elton B. Stephens Company) databases were searched for relevant articles published up to May 2016 that identified common dietary patterns. Thirty-two studies met the inclusion criteria and were finally included in this meta-analysis. A reduced risk of pancreatic cancer was shown for the highest compared with the lowest categories of healthy patterns (odds ratio, OR = 0.86; 95% confidence interval, CI: 0.77-0.95; p = 0.004) and light-moderate drinking patterns (OR = 0.90; 95% CI: 0.83-0.98; p = 0.02). There was evidence of an increased risk for pancreatic cancer in the highest compared with the lowest categories of western-type pattern (OR = 1.24; 95% CI: 1.06-1.45; p = 0.008) and heavy drinking pattern (OR = 1.29; 95% CI: 1.10-1.48; p = 0.002). The results of this meta-analysis demonstrate that healthy and light-moderate drinking patterns may decrease the risk of pancreatic cancer, whereas western-type and heavy drinking patterns may increase the risk of pancreatic cancer. Additional prospective studies are needed to confirm these findings.
... Increased consumption of tea, regular consumption for long periods, and lower temperature of tea were the main factors related to reduction of pancreatic cancer risk for women and nonsmoking men. Particularly for regular consumption habits, the risk of pancreatic cancer is reduced by 32% in women [67] . The study performed by Hsu et al. [68] reported the inverse association of green tea consumption and the risk of nasopharyngeal carcinoma among Taiwan population. ...
Green tea has been an important beverage for humans since ancient times, widely consumed and considered to have health benefits by traditional medicine in Asian countries. Green tea phenolic compounds are predominately composed of catechin derivatives, although other compounds such as flavonols and phenolic acids are also present in lower proportion. The bioactivity exerted by these compounds has been associated with reduced risk of severe illnesses such as cancer, cardiovascular and neurodegenerative diseases. Particularly, epigallocatechin gallate has been implicated in alteration mechanisms with protective effect in these diseases as indicated by several studies about the effect of green tea consumption and mechanistic explanation through in vitro and in vivo experiments. The biological activity of green tea phenolic compounds also promotes a protective effect by antioxidant mechanisms in biological and food systems, preventing the oxidative damage by acting over either precursors or reactive species. Extraction of phenolic compounds influences the antioxidant activity and promotes adequate separation from green tea leaves to enhance the yield and/or antioxidant activity. Application of green tea phenolic compounds is of great interest because the antioxidant status of the products is enhanced and provides the product with additional antioxidant activity or reduces the undesirable changes of oxidative reactions while processing or storing food. In this scenario, meat and meat products are greatly influenced by oxidative deterioration and microbial spoilage, leading to reduced shelf-life. Green tea extracts rich in phenolic compounds have been applied to increase shelf-life with comparable effect to synthetic compounds, commoly used by food industry. Green tea has great importance in general health in technological application, however more studies are necessary to elucidate the impact in pathways related to other diseases and food applications.
... A reduced PC risk was seen in the women who consumed tea for longer durations. These results show that the habit of green tea drinking, including regular drinking, amount of consumption, and persistence of the habit, may lower PC risk [150]. In a placebo-controlled, double-blind clinical trial involving patients undergoing pancreatic duodenectomy, the impact of a preconditioning oral nutritional supplement enriched with glutamine, green tea extract, and antioxidants was evaluated on post-operative oxidative stress. ...
Pancreatic cancer (PC) remains one of the worst cancers, with almost uniform lethality. PC risk is associated with westernized diet, tobacco, alcohol, obesity, chronic pancreatitis, and family history of pancreatic cancer. New targeted agents and the use of various therapeutic combinations have yet to provide adequate treatments for patients with advanced cancer. To design better preventive and/or treatment strategies against PC, knowledge of PC pathogenesis at the molecular level is vital. With the advent of genetically modified animals, significant advances have been made in understanding the molecular biology and pathogenesis of PC. Currently, several clinical trials and preclinical evaluations are underway to investigate novel agents that target signaling defects in PC. An important consideration in evaluating novel drugs is determining whether an agent can reach the target in concentrations effective to treat the disease. Recently, we have reported evidence for chemoprevention of PC. Here, we provide a comprehensive review of current updates on molecularly targeted interventions, as well as dietary, phytochemical, immunoregulatory, and microenvironment-based approaches for the development of novel therapeutic and preventive regimens. Special attention is given to prevention and treatment in preclinical genetically engineered mouse studies and human clinical studies.
... 24,25 However, several studies, including the present study, have shown that increased tea consumption is associated with a reduced risk of pancreatic cancer. 26 A recent population-based case-control study in urban Shanghai drew similar conclusion. 27 Tea contains biologically active compounds, such as catechins, which are believed to influence cancer risk. ...
Background:
Despite having one of the highest mortality rates of all cancers, the risk factors of pancreatic cancer remain unclear. We assessed risk factors of pancreatic cancer in China.
Methods:
A case-control study design was conducted using data from four hospital-based cancer registries (Henan Provincial Cancer Hospital, Beijing Cancer Hospital, Hebei Provincial Cancer Hospital, and Cancer Hospital of Chinese Academy of Medical Sciences). Controls were equally matched and selected from family members of non-pancreatic cancer patients in the same hospitals. Face-to-face interviews were conducted by trained staff using questionnaires. Conditional logistic regression models were used to assess odd ratios (ORs) and 95% confident intervals (CIs).
Results:
Among 646 recruited participants, 323 were pancreatic cancer patients and 323 were controls. Multivariate logistic analysis suggested that pancreatic cancer family history (adjusted OR 1.23; 95% CI, 1.11-3.70), obesity (adjusted OR 1.77; 95% CI, 1.22-2.57), diabetes (adjusted OR 2.96; 95% CI, 1.48-5.92) and smoking (adjusted OR 1.78; 95% CI, 1.02-3.10) were risk factors for pancreatic cancer, but that drinking tea (adjusted OR 0.49; 95% CI, 0.25-0.84) was associated with reduced risk of pancreatic cancer.
Conclusions:
Cigarette smoking, family history, obesity, and diabetes are risk factors of pancreatic cancer, which is important information for designing early intervention and preventive strategies for pancreatic cancer and may be beneficial to pancreatic cancer control in China.
... The current study was conducted within an existing case-control study of pancreatic cancer that has been described previously [24,25] . Briefly, the parent case-control study was performed from December 2006 to January 2011 in urban Shanghai. ...
Pancreatic cancer has been increasing in importance in Shanghai over the last four decades. The etiology of the disease is still unclear. Evidence suggests that the COX-2 pathway, an important component of inflammation, may be involved in the disease. We aimed to evaluate the association between urinary prostaglandin E2 metabolite (PGE-M) level and risk of pancreatic cancer. From a recent population-based case-control study in Shanghai, 200 pancreatic ductal adenocarcinoma cases and 200 gender- and age- frequency matched controls were selected for the present analysis. Urinary PGE-M was measured with a liquid chromatography/mass spectrometric assay. Adjusted unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). A positive association was observed between PGE-M leve and pancreatic cancer risk: OR = 1.63 (95% CI 1.01-2.63) for the third tertile compared to the first. Though the interactions were not statistically significant, the associations tended to be stronger among subjects with diabetes history (OR = 3.32; 95% CI 1.20-9.19) and higher meat intake (OR = 2.12; 95% CI 1.10-4.06). The result suggests that higher urinary PGE-M level may be associated with increased risk of pancreatic ductal adenocarcinoma.
... Another prospective epidemiological study found that the high consumption of cruciferous vegetables and especially of broccoli and cauliflower was associated with a 50 % reduction of the relative risk of developing metastasis in patients with prostate cancer (9). Similarly, a population-based case-control study conducted in urban Shanghai, China, found that regular green tea drinking was associated with a 32% reduction of pancreatic cancer risk in women (10). Well examined bioactive substances from broccoli, cauliflower and green tea involve the isothiocyanate sulforaphane (11), the polyphenol family of catechins (12) and the polyphenol quercetin, which is one of the most abundant flavonoids found in many fruits and vegetables, such as broccoli, apples, onions and berries (13). ...
Pancreatic ductal adenocarcinoma (PDA) has the worst prognosis of all malignancies, and current therapeutic options do not target cancer stem cells (CSCs), which may be the reason for the extreme aggressiveness. The dietary agents sulforaphane and quercetin enriched e.g., in broccoli, and the main and best studied green tea catechin EGCG hold promise as anti-CSC agents in PDA. We examined the efficacy of additional catechins and the combination of these bioactive agents to stem cell features and miRNA signaling. Two established and one primary PDA cell line and non-malignant pancreatic ductal cells were used. Whereas each agent strongly inhibited colony formation, the catechins ECG and CG were more effective than EGCG. A mixture of green tea catechins (GTCs) significantly inhibited viability, migration, expression of MMP-2 and -9, ALDH1 activity, colony and spheroid formation and induced apoptosis, but the combination of GTCs with sulforaphane or quercetin was superior. Following treatment with bioactive agents, the expression of miR-let7-a was specifically induced in cancer cells but not in normal cells and it was associated with K-ras inhibition. These data demonstrate that sulforaphane, quercetin and GTC complement each other in inhibition of PDA progression by induction of miR-let7-a and inhibition of K-ras.
... It can be seen that antineoplastic and antihypertensive are the most common predicted activities of the four polyphenols, which agree well with the health benefits of their dietary sources. For instance, accumulating evidence indicated that high soybean intake and regular green tea drinking are associated with low incidence rates of human cancers and hypertension [23][24][25][26][27][28]. In addition, a large part (50%) of the predicted targets of these polyphenols are validated by experiments, most (92.3%) of which are direct targets (Tables 1-4). ...
Due to the diverse medicinal effects, polyphenols are among the most intensively studied natural products. However, it is a great challenge to elucidate the polypharmacological mechanisms of polyphenols. To address this challenge, we establish a method for identifying multiple targets of chemical agents through analyzing the module profiles of gene expression upon chemical treatments. By using FABIA algorithm, we have performed a biclustering analysis of gene expression profiles derived from Connectivity Map (cMap), and clustered the profiles into 49 gene modules. This allowed us to define a 49 dimensional binary vector to characterize the gene module profiles, by which we can compare the expression profiles for each pair of chemical agents with Tanimoto coefficient. For the agent pairs with similar gene expression profiles, we can predict the target of one agent from the other. Drug target enrichment analysis indicated that this method is efficient to predict the multiple targets of chemical agents. By using this method, we identify 148 targets for 20 polyphenols derived from cMap. A large part of the targets are validated by experimental observations. The results show that the medicinal effects of polyphenols are far beyond their well-known antioxidant activities. This method is also applicable to dissect the polypharmacology of other natural products.
... Over the past decades, intensive research brought forth a deeper understanding of pancreatic carcinoma formation and outgrowth, giving rise to sophisticated therapies of suffering patients. However, the overall prognosis of pancreatic cancer is still very poor, with the 1-year survival rate of less than 20% and a 5-year survival rate of less than 5% [19][20][21]. Accumulating data support the concept that the capability of the tumor to grow and propagate is dependent on a small subset of cells within a tumor, termed cancer stem cells and/or progenitor cells. CSCs represent a small population of cancer cells that exhibit self-renewal and differentiation characteristics. ...
Cancer stem cells (CSCs) or cancer-initiating cells (CICs) play an important role in tumor initiation, progression, metastasis, chemoresistance, and recurrence. It is important to construct an effective method to identify and isolate CSCs for biotherapy of cancer. During the past years, many researchers had paid more attention to it; however, this method was still on seeking. Therefore, compared to the former methods that were used to isolate the cancer stem cell, in the present study, we tried to use modified transwell system to isolate and enrich CSCs from human pancreatic cancer cell lines (Panc-1). Our results clearly showed that the lower chamber cells in modified transwell system were easily forming spheres; furthermore, these spheres expressed high levels of stem cell markers (CD133/CD44/CD24/Oct-4/ESA) and exhibited chemoresistance, underwent epithelial-to-mesenchymal transition (EMT), and possessed the properties of self-renewal in vitro and tumorigenicity in vivo. Therefore, we speculated that modified transwell assay system, as a rapid and effective method, can be used to isolate and enrich CSCs.
... The preventive and inhibitory activities of Camellia sinensis and its chemical constituents against carcinogenesis at different organs have been demonstrated in many animal models and cell culture systems [21,[84][85][86][87]. On the other hand, although several studies suggest a reduction of cancer risk in humans induced by tea consumption, especially green tea [88][89][90], the results have not been consistent [88,91]. ...
... All participants were long-term residents of Shanghai and between 35 and 79 y of age. Details of the study design and participant recruitment have been described elsewhere (11). Briefly, 908 incident cases were recruited via an ''instant case reporting system'' in 37 urban Shanghai hospitals. ...
Regular consumption of energy-dense foods predisposes to obesity and type 2 diabetes, both of which are suggested risk factors for pancreatic cancer. The aim of this study was to investigate whether energy density of foods is an independent risk factor for pancreatic cancer. In this population-based case-control study in urban Shanghai, 908 patients with pancreatic cancer and 1067 normal controls, aged 35-79 y, were recruited. The energy density for overall diet was calculated from food-frequency questionnaire data. Energy density (adjusted for age, sex, and total energy intake) was significantly higher in cases (6.08 ± 0.04 kJ/g) than in controls (5.91 ± 0.04 kJ/g) (P = 0.003). Energy density was positively associated with pancreatic cancer risk (OR: 1.16 per unit increase; 95% CI: 1.07, 1.27; P < 0.001). In adjusted analysis, the risk of pancreatic cancer was 72% greater (OR: 1.72; 95% CI: 1.25, 2.35; P = 0.001) in the highest quintile of energy density compared with the lowest quintile. In this case-control study, dietary energy density is positively associated with risk of pancreatic cancer. This association should be further investigated in prospective studies.
... Between December 2006 and January 2011, subjects were enrolled in a population-based case-control study of pancreatic cancer in urban Shanghai, China as described in a previous report [11] . All participants were Shanghai residents between 35 and 79 years of age. ...
Pancreatic cancer is a fatal malignancy with an increasing incidence in Shanghai, China. A genome-wide association study (GWAS) and other work have shown that ABO alleles are associated with pancreatic cancer risk. We conducted a population-based case-control study involving 256 patients with pathologically confirmed pancreatic ductal adenocarcinoma (PDAC) and 548 healthy controls in Shanghai, China, to assess the relationships between GWAS-identified ABO alleles and risk of PDAC. Carriers of the C allele of rs505922 had an increased cancer risk [adjusted odds ratio (OR) = 1.42, 95% confidence interval (CI): 1.02-1.98] compared to TT carriers. The T alleles of rs495828 and rs657152 were also significantly associated with an elevated cancer risk (adjusted OR = 1.58, 95% CI: 1.17-2.14; OR = 1.51, 95% CI: 1.09-2.10). The rs630014 variant was not associated with risk. We did not find any significant gene-environment interactions with cancer risk using a multifactor dimensionality reduction (MDR) method. Haplotype analysis also showed that the haplotype CTTC was associated with an increased risk of PDAC (adjusted OR = 1.46, 95% CI: 1.12-1.91) compared with haplotype TGGT. GWAS-identified ABO variants are thus also associated with risk of PDAC in the Chinese population.
... Regular green tea drinking was associated with 32% reduction of pancreatic cancer risk as compared to those who did not drink tea regularly in women with increased consumption and longer duration of tea drinking associated with reduced pancreatic cancer risk. Lower temperature of tea was associated with reduced risk of pancreatic cancer in both men and women, irrespective of the amount or duration of tea drinking among regular tea drinkers [43]. In case control studies on the relationship between gastric cancer and tea consumption conducted in China and Japan, a significant inverse relationship was found in four studies and an insignificant inverse relationship was found in two studies [44]. ...
Tea, next to water is the cheapest beverage humans consume. Drinking the beverage tea has been considered a health-promoting habit since ancient times. The modern medicinal research is providing a scientific basis for this belief. The evidence supporting the health benefits of tea drinking grows stronger with each new study that is published in the scientific literature. Tea plant Camellia sinensis has been cultivated for thousands of years and its leaves have been used for medicinal purposes. Tea is used as a popular beverage worldwide and its ingredients are now finding medicinal benefits. Encouraging data showing cancer-preventive effects of green tea from cell-culture, animal and human studies have emerged. Evidence is accumulating that black tea may have similar beneficial effects. Tea consumption has also been shown to be useful for prevention of many debilitating human diseases that include maintenance of cardiovascular and metabolic health. Various studies suggest that polyphenolic compounds present in green and black tea are associated with beneficial effects in prevention of cardiovascular diseases, particularly of atherosclerosis and coronary heart disease. In addition, anti-aging, antidiabetic and many other health beneficial effects associated with tea consumption are described. Evidence is accumulating that catechins and theaflavins, which are the main polyphenolic compounds of green and black tea, respectively, are responsible for most of the physiological effects of tea. This article describes the evidences from clinical and epidemiological studies in the prevention of chronic diseases like cancer and cardiovascular diseases and general health promotion associated with tea consumption.
Brown seaweeds have been used in phytotherapy since ancient times [Hoppe et al. 1979; Liu et al. 2012]. In recent years, a multitude of medical effects have been reported for this group of algae and
for their isolated substances that also cover anti-tumor activities [Gupta and Abu-Ghannam 2011]. Though being the most common and most conspicuous brown seaweed species in the Baltic Sea [Kautsky et al. 1992], nothing was known, so far, about the anti-cancer potential of the Bladderwrack, Fucus vesiculosus L., grown in this particular habitat with low salinity and non-tidal shores [Rheinheimer 1996].
With the present work which was part of the national research project “Algae against Cancer (AAC)” this knowledge gap should be closed. The AAC-project, funded by the Federal Ministry of Education and Research (BMBF) from 2010 to 2013, was in one of its two parts dedicated to the examination of the anti-cancer potential of the Baltic Sea F. vesiculosus [Zenthoefer et al. 2017] followed by the
elucidation of the cellular mechanisms of the anti-cancer effect that one verifiably active F. vesiculosus extract induced in pancreatic cancer cell lines [Geisen et al. 2015].
In detail, the objectives of the present work were to provide a systematic analysis of the cytotoxic activity of F. vesiculosus against the two pancreatic ductal adenocarcinoma cell lines Panc89 and
PancTU1 and for a detected anti-cancer activity, a tailor-made extraction and purification procedure should be developed and implemented. To come closer to these objectives, a bioassay-guided
fractionation approach was used in which all initial crude extracts and successively produced fractions were examined for their activity in a 72 h viability assay (XTT assay) and monitored for their ingredients using 1H-NMR spectroscopy.
Six different crude extracts were prepared from freshly frozen algae material collected from the Kiel Fjord, Western Baltic Sea, at late springtime. Four out of these six crude extracts showed considerable cytotoxic activity against the Panc89 cells and three out of them were active against the PancTU1 cells. The most active crude extract, FvT_A, prepared from central parts of the thallus of the alga by the use of acetone at the rate of 1:2 (w/v) revealed a half maximal effective concentration (IC50) of 72 and 77 µg/ml, respectively, against the Panc89 and PancTU1 cells in the standard XTT assay. For FvT_A, a multistep fractionation and purification procedure was implemented consisting of the processes precipitation, normal-Phase chromatography on a Pharmprep60CC SiO2 and reversed
phase chromatography on Amberlite® XAD7HP. This purification scheme resulted in a fourfold reduction of the IC50 from the crude extract to the most active fractions F15/F16. Evaluation of all 1H
NMR spectra revealed a characteristic fingerprint which significantly correlated with the anti-cancer activity. Structural analysis using different methods of NMR spectroscopy as well as IR and UV
spectroscopy revealed for the active compounds in F15/F16 two similar molecules with a molecular weight of 1331 (±5 %) and 1173 (±5 %) g/mol which belong to the group of polyphenols and are most probably phlorotannins. However, further separation of F15/F16 and further structural analysis is needed in order to present the chemical structure in all details. In summary, the results show that F. vesiculosus from the Baltic Sea holds potent anti-cancer substances. The findings are promising as they are not only technically but also biologically reproducible and the isolated active substances
seem to be as yet unknown.
Background:
This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (2009, Issue 3).Tea is one of the most commonly consumed beverages worldwide. Teas from the plant Camellia sinensis can be grouped into green, black and oolong tea, and drinking habits vary cross-culturally. C sinensis contains polyphenols, one subgroup being catechins. Catechins are powerful antioxidants, and laboratory studies have suggested that these compounds may inhibit cancer cell proliferation. Some experimental and nonexperimental epidemiological studies have suggested that green tea may have cancer-preventative effects.
Objectives:
To assess possible associations between green tea consumption and the risk of cancer incidence and mortality as primary outcomes, and safety data and quality of life as secondary outcomes.
Search methods:
We searched eligible studies up to January 2019 in CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and reference lists of previous reviews and included studies.
Selection criteria:
We included all epidemiological studies, experimental (i.e. randomised controlled trials (RCTs)) and nonexperimental (non-randomised studies, i.e. observational studies with both cohort and case-control design) that investigated the association of green tea consumption with cancer risk or quality of life, or both.
Data collection and analysis:
Two or more review authors independently applied the study criteria, extracted data and assessed methodological quality of studies. We summarised the results according to diagnosis of cancer type.
Main results:
In this review update, we included in total 142 completed studies (11 experimental and 131 nonexperimental) and two ongoing studies. This is an additional 10 experimental and 85 nonexperimental studies from those included in the previous version of the review. Eleven experimental studies allocated a total of 1795 participants to either green tea extract or placebo, all demonstrating an overall high methodological quality based on 'Risk of bias' assessment. For incident prostate cancer, the summary risk ratio (RR) in the green tea-supplemented participants was 0.50 (95% confidence interval (CI) 0.18 to 1.36), based on three studies and involving 201 participants (low-certainty evidence). The summary RR for gynaecological cancer was 1.50 (95% CI 0.41 to 5.48; 2 studies, 1157 participants; low-certainty evidence). No evidence of effect of non-melanoma skin cancer emerged (summary RR 1.00, 95% CI 0.06 to 15.92; 1 study, 1075 participants; low-certainty evidence). In addition, adverse effects of green tea extract intake were reported, including gastrointestinal disorders, elevation of liver enzymes, and, more rarely, insomnia, raised blood pressure and skin/subcutaneous reactions. Consumption of green tea extracts induced a slight improvement in quality of life, compared with placebo, based on three experimental studies. In nonexperimental studies, we included over 1,100,000 participants from 46 cohort studies and 85 case-control studies, which were on average of intermediate to high methodological quality based on Newcastle-Ottawa Scale 'Risk of bias' assessment. When comparing the highest intake of green tea with the lowest, we found a lower overall cancer incidence (summary RR 0.83, 95% CI 0.65 to 1.07), based on three studies, involving 52,479 participants (low-certainty evidence). Conversely, we found no association between green tea consumption and cancer-related mortality (summary RR 0.99, 95% CI 0.91 to 1.07), based on eight studies and 504,366 participants (low-certainty evidence). For most of the site-specific cancers we observed a decreased RR in the highest category of green tea consumption compared with the lowest one. After stratifying the analysis according to study design, we found strongly conflicting results for some cancer sites: oesophageal, prostate and urinary tract cancer, and leukaemia showed an increased RR in cohort studies and a decreased RR or no difference in case-control studies.
Authors' conclusions:
Overall, findings from experimental and nonexperimental epidemiological studies yielded inconsistent results, thus providing limited evidence for the beneficial effect of green tea consumption on the overall risk of cancer or on specific cancer sites. Some evidence of a beneficial effect of green tea at some cancer sites emerged from the RCTs and from case-control studies, but their methodological limitations, such as the low number and size of the studies, and the inconsistencies with the results of cohort studies, limit the interpretability of the RR estimates. The studies also indicated the occurrence of several side effects associated with high intakes of green tea. In addition, the majority of included studies were carried out in Asian populations characterised by a high intake of green tea, thus limiting the generalisability of the findings to other populations. Well conducted and adequately powered RCTs would be needed to draw conclusions on the possible beneficial effects of green tea consumption on cancer risk.
Background/Aims: Dietary patterns have been used to explore the association between dietary factors and risk of pancreatic (PC) and renal cancer (RC); however, the association remains unclear. This meta-analysis was performed to comprehensively analyze these associations.
Methods: Pertinent studies published prior to March 2016 were systematically searched and retrieved through PubMed and Scopus databases. Adjusted risk estimates were derived by comparing the highest with the lowest categories of dietary pattern scores and were combined by usaing the fixed-effects model when no substantial heterogeneity was observed; otherwise, the random-effects model was employed.
Results: A total of 9 studies, 5 for pancreatic cancer (including 2059 cases and 41774 participants/controls) and 4 for renal cancer (with 1327 cases and 53007 participants/controls) were included in this meta-analysis. A decreased risk of PC was shown for the highest compared with the lowest categories of the healthy dietary pattern (OR=0.72, 95%CI= 0.51–0.94, random effects (P-value for heterogeneity = 0.004)), whereas no significant association with Western pattern was observed (OR=1.16, 95% CI=0.87-1.44, fixed effects). In the overall analysis, a significant association was found between the healthy dietary pattern and reduced risk of RC (OR=0.59, 95%CI=0.48-0.71, fixed effects (P-value for heterogeneity = 0.459)), while the Western pattern was positively associated with risk of RC (OR=1.42, 95%CI=1.14-1.69, fixed effects). For both cancers, the reduced risk accociated with the healthy pattern was restricted to case-control, but not cohort, studies. Furthermore, drinking pattern was significantly related to reduced risk of RC (OR=0.68, 95%CI=0.42-0.94).
Conclusion: A healthy dietary pattern might be associated with a lower risk of pancreatic and renal cancer.
Abstract Neoplastic conditions associated with gastrointestinal (GI) tract are common worldwide with colorectal cancer alone accounting for the third leading rate of cancer incidence. Other GI malignancies such as esophageal carcinoma have shown an increasing trend in the last few years. The poor survival statistics of these fatal cancer diseases highlight the need for multiple alternative treatment options along with effective prophylactic strategies. Worldwide geographical variation in cancer incidence indicates a correlation between dietary habits and cancer risk. Epidemiological studies have suggested that populations with high intake of certain dietary agents in their regular meals have lower cancer rates. Thus an impressive embodiment of evidence supports the concept that dietary factors are key modulators of cancer including those of GI origin. Preclinical studies on animal models of carcinogenesis have reflected the pharmacological significance of certain dietary agents called as nutraceuticals in the chemoprevention of GI neoplasia. These include stilbenes (from red grapes and red wine), isoflavones (from soy), carotenoids (from tomatoes), curcuminoids (from spice turmeric), catechins (from green tea) and various other small plant metabolites (from fruits, vegetables and cereals). Pleiotropic action mechanisms have been reported for these diet-derived chemopreventive agents to retard, block or reverse carcinogenesis. This review presents a prophylactic approach to primary prevention of GI cancers by highlighting the translational potential of plant-derived nutraceuticals from epidemiological, laboratory and clinical studies, for the better management of these cancers through consumption of nutraceutical rich diets and their intervention in cancer therapeutics.
Background:
Epidemiologic studies have reported inconsistent results regarding tea consumption and the risk of pancreatic cancer. This study aimed to investigate whether tea consumption is related to the risk of pancreatic cancer.
Methods:
We searched Medline, EMBASE, ISI Web of Science, and the Cochrane library for studies published up to November 2013. We used a meta-analytic approach to estimate overall odds ratio (OR) and 95% confidence interval (CI) for the highest versus the lowest tea consumption categories.
Results:
The summary OR for high versus no/almost never tea drinkers was 1.04 (95% CI: 0.91-1.20), with no significant heterogeneity across studies (P = 0.751; I(2) = 0.0%). The OR was 0.99 (95% CI: 0.77-1.28) in males and 1.01 (95% CI: 0.79-1.29) in females. The OR was 1.07 (95% CI: 0.85-1.34) in Asian studies, 1.05 (95% CI: 0.84-1.31) in European studies, and 0.98 (95% CI: 0.72-1.34) in the US studies. The OR was 0.87 (95% CI: 0.69-1.10) without adjustment for a history of diabetes and 1.16 (95% CI: 0.97-0.39) after adjustment for a history of diabetes. The OR was 0.90 (95% CI: 0.72-1.12) without adjustment for alcohol drinking and 1.16 (95% CI: 0.96-1.39) after adjustment for alcohol drinking. The OR was 0.97 (95% CI: 0.76-1.25) without adjustment for BMI and 1.07 (95% CI: 0.87-1.31) after adjustment for BMI.
Conclusion:
This systematic meta-analysis of cohort studies dose not provide quantitative evidence that tea consumption is appreciably related to the risk of pancreatic cancer, even at high doses.
Epidemiologic studies on the relationship between tea consumption and pancreatic cancer are inconsistent. Therefore, we conducted a systematic search of databases and performed a meta-analysis to analyze the association between tea consumption and risk of pancreatic cancer. We searched Medline, EMBASE, ISI Web of Science, and the Cochrane library for studies of tea consumption and pancreatic cancer published up to December 2012. Subgroup analysis was conducted by study type, study region, sex, type of tea, without or with adjustment for smoking, and body mass index. We performed a meta-analysis of 8 case-control studies and 6 cohort studies. For pancreatic cancer, the summary odds ratio (OR) for highest vs. lowest was 0.95 (95% confidence interval (CI), 0.84-1.08). The summary OR for moderate vs. lowest was 1.07 (95% CI, 0.86-1.35). The summary OR for ever vs. lowest was 1.00 (95% CI, 0.86-1.16). The results of this meta-analysis suggested tea consumption is not related to pancreatic cancer risk, even at high doses. Because of the small number of studies, further prospective studies are needed.
Pancreatic cancer has a poor prognosis with a 5-year survival rate of <5%. It does not respond well to either chemotherapy or radiotherapy, due partly to cancer cell apoptotic resistance (AR). AR has been attributed to certain genetic abnormalities or defects in apoptotic signaling pathways. In pancreatic cancer, significant mutations of K-ras and p53, constitutive activation of NFκB, over-expression of heat shock proteins (Hsp90, Hsp70), histone deacetylase (HDACs) and the activities of other proteins (COX-2, Nrf2 and bcl-2 family members) are closely linked with resistance to apoptosis and invasion. AR has also been associated with aberrant signaling of MAPK, PI3K-AKT, JAK/STAT, SHH, Notch, and Wnt/β-catenin pathways. Strategies targeting these signaling molecules and pathways provide an alternative for overcoming pancreatic cancer AR. The use of herbal medicines or natural products (HM/NPs) alone or in combination with conventional anti-cancer agents has been shown to produce beneficial effects through actions upon multiple molecular pathways involved in AR. The current standard first-line chemotherapeutic agents for pancreatic cancer are gemcitabine (Gem) or Gem-containing combinations; however, the efficacy is dissatisfied and this limitation is largely attributed to resistance to apoptosis. Meanwhile, emerging data have pointed to a combination of HM/NPs that may augment the sensitivity of pancreatic cancer cells to Gem. Greater understanding of how these compounds affect the molecular mechanisms of apoptosis may propel development of HM/NPs as anti-cancer agents and/or adjuvant therapies forward. In this review, we give a critical appraisal of the use of HM/NPs alone and in combination with anti-cancer drugs. We also discuss the potential regulatory mechanisms whereby AR is involved in these protective pathways.
The aim of this study was to evaluate the relationship between regular tea consumption and the risk of pancreatic cancer by a meta-analysis. Two investigators independently performed a computer retrieve on the electronic databases of Embase, PubMed, and Ovidsp for prospective cohort studies and case-control studies on regular tea consumption and the risk of pancreatic cancer incidence. The keywords using for search were ('Pancreas' OR 'pancreatic') AND ('neoplasms' OR 'carcinoma' OR 'cancer') AND 'tea'. Risk ratios (RRs) and 95% confidence interval (CI) were used to determine the effect of tea consumption on pancreatic cancer. A total of 14 studies were included (8078 pancreatic cancer patients, with a total of 859 783 patients) in the present meta-analysis. The pooled results of effect size indicated that tea consumption has no significant relationship with risk of pancreatic cancer (RR=0.99, 95% CI: 0.89-1.11, P=0.922). However, the subgroup analysis of different countries showed a statistical decrease in pancreatic cancer risk by high consumption of tea in a Chinese population (RR=0.76, 95% CI: 0.59-0.98, P=0.036). Similar results were found in the elderly (>60 years old) (RR=0.76, 95% CI: 0.60-0.96, P=0.023). In conclusion, the present meta-analysis of 14 studies suggests that the correlation between tea consumption and the risk of pancreatic cancer in the general population is not significant, but an increase in tea consumption can reduce the risk of pancreatic cancer disease in Chinese populations and in individuals older than 60 years of age. It is necessary to formulate more rigorous designs of regional studies to further confirm the relationship between tea consumption and pancreatic cancer.
A multi-center population-based study in Shanghai, China was performed to explore the implications for the management of pancreatic cancer by comparing diagnosis and survival rates. Novel imaging modalities including MRI (13.9%), PET/CT (1.8%), and EUS (5.6%) were not widely used in our population. Only 39.7% of cases were histologically verified (surgery with histologic diagnosis 31.0%, cytological diagnosis 8.7%, surgery without histologic diagnosis 12.1%, and clinical diagnosis 48.2%). Overall, 30.0% of patients underwent curative-intent operation, and only 9.8% of patients received comprehensive treatment. The prognosis of pancreatic cancer patients was significantly better for patients who were treated in high-volume centers than in low-volume centers. We propose that more effort should be put on novel diagnostic modalities, histological confirmation, and comprehensive treatment in China. Multidisciplinary teams specialized in pancreatic cancer therapy in high-volume centers are urgently needed.
Pancreatic cancer is the fourth leading cause of cancer death in men and women. Prognosis is poor with a 5-year survival rate of less than 5%. As there is no effective screening modality, the best way to reduce morbidity and mortality due to pancreatic cancer is by effective primary prevention. Aim: To evaluate the role of dietary components in pancreatic cancer.
Bibliographical searches were performed in PubMed using the terms "pancreatic cancer", together with "nutrition", "diet", "dietary factors", "lifestyle", "smoking", "alcohol" and "epidemiology".
Fruits (particularly citrus) and vegetable consumption may be beneficial. The consumption of whole grains has been shown to reduce pancreatic cancer risk and fortification of whole grains with folate may confer further protection. Red meat, cooked at high temperatures, should be avoided, and replaced with poultry or fish. Total fat should be reduced. The use of curcumin and other flavonoids should be encouraged in the diet. There is no evidence for benefit from vitamin D supplementation. There may be benefit for dietary folate. Smoking and high Body Mass Index have both been inversely associated with pancreatic cancer risk.
The lack of randomized trials and the presence of confounding factors including smoking status, physical activity, distance of habitat from the equator, obesity, and diabetes may often result in inconclusive results. There is evidence to encourage the use of whole grain in the staple diet and supplementation within the diet of folate, curcumin and other flavanoids. Carefully designed randomized trials are required to further elucidate these important matters.
Tea and its constituents have demonstrated anticarcinogenic activity in both in vitro and in vivo animal studies. Results from epidemiologic studies, however, have been inconsistent. Some factors that coexist with tea consumption, such as cigarette smoking, may confound or modify the association between tea consumption and cancer risk. The objective of this study was to comprehensively evaluate the association between green tea consumption and colorectal cancer risk in a population-based prospective cohort study, the Shanghai Men's Health Study. The analysis included 60,567 Chinese men aged 40-74 years at baseline. During ∼5 years of follow-up, 243 incident cases of colorectal cancer were identified. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of developing colorectal cancer. Regular green tea consumption (ever drank green tea at least three times per week for more than six consecutive months) was associated with reduced risk of colorectal cancer in non-smokers (multivariable-adjusted HR = 0.54, 95% CI: 0.34-0.86). The risk decreased as the amount of green tea consumption increased (P(trend) = 0.01). Each 2 g increment of intake of dry green tea leaves per day (approximately equivalent to the amount of tea in a tea bag) was associated with a 12% reduction in risk (HR = 0.88, 95% CI: 0.78-0.99). No significant association was found among smokers (HR = 0.94, 95% CI: 0.66-1.34). This study suggests that regular consumption of green tea may reduce colorectal cancer risk among non-smokers.
Smoking is an established risk factor for pancreatic cancer; however, detailed examination of the association of smoking intensity, smoking duration, and cumulative smoking dose with pancreatic cancer is limited. The authors analyzed pooled data from the international Pancreatic Cancer Cohort Consortium nested case-control study (1,481 cases, 1,539 controls). Odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression. Smoking intensity effects were examined with an excess odds ratio model that was linear in pack-years and exponential in cigarettes smoked per day and its square. When compared with never smokers, current smokers had a significantly elevated risk (odds ratio (OR) = 1.77, 95% confidence interval (CI): 1.38, 2.26). Risk increased significantly with greater intensity (> or =30 cigarettes/day: OR = 1.75, 95% CI: 1.27, 2.42), duration (> or =50 years: OR = 2.13, 95% CI: 1.25, 3.62), and cumulative smoking dose (> or =40 pack-years: OR = 1.78, 95% CI: 1.35, 2.34). Risk more than 15 years after smoking cessation was similar to that for never smokers. Estimates of excess odds ratio per pack-year declined with increasing intensity, suggesting greater risk for total exposure delivered at lower intensity for longer duration than for higher intensity for shorter duration. This finding and the decline in risk after smoking cessation suggest that smoking has a late-stage effect on pancreatic carcinogenesis.
To evaluate the validity and reliability of the food frequency questionnaire (FFQ) used in the Shanghai Women's Health Study (SWHS), 200 SWHS participants were recruited for a dietary calibration study. Study participants completed an FFQ at baseline and 24-h dietary recalls (24-HDR) twice per month consecutively for 12 months. At the end of the study, a second FFQ was administered. Of the 200 study participants, 196 completed 24 or more days of 24-h dietary recalls, 191 completed two FFQs from whom the results of this report were based. The FFQ included the foods that accounted for 86% of the foods recorded in the 24-HDR surveys. Validity of the FFQ was evaluated by comparing intake levels of major nutrients and foods obtained from the second FFQ with those derived from the multiple 24-HDR. The median intake for major nutrients, rice, poultry and meat derived from the second FFQ and the 24-HDR was similar, with the differences ranging from 1.3 to 12.1%. The FFQ tended to overestimate the intake level of total vegetables and total fruits, and the differences were explained mainly by over-reporting seasonal vegetables and fruits consumption in the FFQ. Nutrient and food intake assessed by the FFQ and the multiple 24-HDR correlated very well, with the correlation coefficients being 0.59-0.66 for macronutrients, 0.41-0.59 for micronutrients, and 0.41-0.66 for major food groups. The reliability of the FFQ was assessed by comparing the correlation and median intake of nutrients and food groups obtained from the two FFQs that were administered approximately 2 y apart. The median intake levels for selected nutrients and food groups derived from the two FFQs were similar with differences below 10%. At the individual level, the intake levels of these dietary variables obtained from two FFQs also correlated well. When nutrient and food group intakes were categorized into quartiles, FFQ and 24-HDR produced exact agreement rates between 33 and 50%. Misclassification to adjacent quartile was common, ranging from 34-48%, while misclassification to an extreme quartile was rare (1-6%). These data indicate that the SWHS FFQ can reliably and accurately measure usual intake of major nutrients and food groups among women in Shanghai.
The effect of green tea drinking in reducing human cancer risk is unclear, though a protective effect has been reported in numerous animal studies and several epidemiologic investigations. Herein the hypothesis that green tea consumption may reduce the risk of cancers of the colon, rectum and pancreas is examined in a large population-based case-control study conducted in Shanghai, China. Newly diagnosed cancer cases (931 colon, 884 rectum and 451 pancreas) during 1990–1993 among residents 30–74 years of age were included. Controls (n = 1,552) were selected among Shanghai residents and frequency-matched to cases by gender and age. Multivariate odds ratios (ORs) and 95% confidence intervals (Cls) of each cancer associated with green tea consumption were derived after adjustment for age, income, education and cigarette smoking. Additional adjustment for dietary items and body size was found to have minimal impact. An inverse association with each cancer was observed with increasing amount of green tea consumption, with the strongest trends for rectal and pancreatic cancers. For men, compared with non-regular tea drinkers, ORs among those in the highest tea consumption category (≥300 g/month) were 0.82 for colon cancer, 0.72 for rectal cancer and 0.63 for pancreatic cancer, with p values for trend being 0.38, 0.04 and 0.04, respectively. For women, the respective ORs for the highest consumption category (≥200 g/month) were 0.67, 0.57 and 0.53, with the respective p values for trend being 0.07, 0.001 and 0.008. Our findings provide further evidence that green tea drinking may lower the risk of colorectal and pancreatic cancers. Int. J. Cancer, 70:255–258, 1997. © 1997 Wiley-Liss, Inc.†
Green tea catechins are considered as possible cancer preventive agents for several cancer types but little is known regarding their effects on pancreatic cancer cells. The best studied catechin and the major polyphenol present in green tea is epigallocatechin gallate (EGCG). In the present study, we investigated the in vitro anti-tumoral properties of EGCG on human pancreatic ductal adenocarcinoma (PDAC) cells PancTu-I, Panc1, Panc89 and BxPC3 in comparison with the effects of two minor components of green tea catechins, catechin gallate (CG) and epicatechin gallate (ECG). We found that all three catechins inhibited proliferation of PDAC cells in a dose- and time-dependent manner. Interestingly, CG and ECG exerted much stronger anti-proliferative effects than EGCG. Western blot analyses performed with PancTu-I cells revealed catechin-mediated modulation of cell cycle regulatory proteins (cyclins, cyclin-dependent kinases [CDK], CDK inhibitors). Again, these effects were clearly more pronounced in CG or ECG than in EGCG-treated cells. Importantly, catechins, in particular ECG, inhibited TNFα-induced activation of NF-κB and consequently secretion of pro-inflammatory and invasion promoting proteins like IL-8 and uPA. Overall, our data show that green tea catechins ECG and CG exhibit potent and much stronger anti-proliferative and anti-inflammatory activities on PDAC cells than the most studied catechin EGCG.
Background:
Studies in laboratory animals have suggested inhibitory effects of green tea on the induction of some cancers, notably, esophageal cancer. However, only a few epidemiologic studies have evaluated green tea as a potential inhibitor of human esophageal cancer.
Purpose:
Our purpose was to evaluate the relationship between green tea consumption and the risk of esophageal cancer.
Methods:
This esophageal cancer study was part of a larger multicenter, case-control study that included three other gastrointestinal sites (pancreas, colon, and rectum). Medical records of patients aged 30-74 years old who were diagnosed with esophageal cancer from October 1, 1990, through January 31, 1993, were identified from the Shanghai Cancer Registry, which covers 6.8 million people in the urban area of Shanghai, People's Republic of China. During the ascertainment period, records of 1016 eligible cases of esophageal cancer were identified. Control subject records were selected by frequency matching in accordance with the age-sex distribution of the four gastrointestinal cancers ascertained by the cancer registry during 1986-1987. Patient interviews were then conducted using a structured, standardized questionnaire to obtain information on demographic characteristics, residential history, height and weight, diet, smoking, alcohol and tea drinking, medical history, family history of cancer, occupation, physical activity, and reproductive history.
Results:
Of the 902 patients interviewed, 734 (81.4%) had their disease pathologically confirmed. There were 1552 control subjects interviewed, including 240 alternates. All analyses of tea effects were conducted separately among men and women and all were adjusted for age. After further adjustment for other known confounders, a protective effect of green tea drinking on esophageal cancer was observed among women (odds ratio [OR] = 0.50; 95% confidence interval [CI] = 0.30-0.83), and this risk decreased (P for trend < or = .01) as tea consumption increased. Among men, the ORs were also below 1.00, although not statistically significant. ORs for green tea intake were estimated among those persons who neither smoked nor drank alcohol. In this subset, statistically significant decreases in risk among tea drinkers were observed for both men (OR = 0.43; 95% CI = 0.22-0.86; P for trend = .05) and women (OR = 0.40; 95% CI = 0.20-0.77; P for trend < .001).
Conclusions:
This population-based, case-control study of esophageal cancer in urban Shanghai suggests a protective effect of green tea consumption. Although these findings are consistent with studies in laboratory animals, indicating that green tea can inhibit esophageal carcinogenesis, further investigations are definitely needed.
Each year, the American Cancer Society estimates the number of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. Incidence and death rates are standardized by age to the 2000 United States standard million population. A total of 1,479,350 new cancer cases and 562,340 deaths from cancer are projected to occur in the United States in 2009. Overall cancer incidence rates decreased in the most recent time period in both men (1.8% per year from 2001 to 2005) and women (0.6% per year from 1998 to 2005), largely because of decreases in the three major cancer sites in men (lung, prostate, and colon and rectum [colorectum]) and in two major cancer sites in women (breast and colorectum). Overall cancer death rates decreased in men by 19.2% between 1990 and 2005, with decreases in lung (37%), prostate (24%), and colorectal (17%) cancer rates accounting for nearly 80% of the total decrease. Among women, overall cancer death rates between 1991 and 2005 decreased by 11.4%, with decreases in breast (37%) and colorectal (24%) cancer rates accounting for 60% of the total decrease. The reduction in the overall cancer death rates has resulted in the avoidance of about 650,000 deaths from cancer over the 15-year period. This report also examines cancer incidence, mortality, and survival by site, sex, race/ethnicity, education, geographic area, and calendar year. Although progress has been made in reducing incidence and mortality rates and improving survival, cancer still accounts for more deaths than heart disease in persons younger than 85 years of age. Further progress can be accelerated by applying existing cancer control knowledge across all segments of the population and by supporting new discoveries in cancer prevention, early detection, and treatment.
Extracts of tea, especially green tea, and tea polyphenols have been shown to inhibit the formation and development of tumours at different organ sites in animal models. There is considerable evidence that tea polyphenols, in particular (-)-epigallocatechin-3-gallate, inhibit enzyme activities and signal transduction pathways, resulting in the suppression of cell proliferation and enhancement of apoptosis, as well as the inhibition of cell invasion,angiogenesis and metastasis. Here, we review these biological activities and existing data relating tea consumption to human cancer risk in an attempt to understand the potential use of tea for cancer prevention.
Four hundred and ninety pancreas cancer patients representative of confirmed cases in Los Angeles County residents of working age were compared to healthy controls individually matched by age, sex, race, and neighborhood. Home interviews were conducted on occupation, smoking, food and beverage consumption, and medical history. Cigarette smoking was a strong and consistent predictor of pancreas cancer occurrence; the effect disappeared after a decade of nonsmoking, and there was no increase in risk among current smokers as daily dose increased. There was no link between pancreas cancer and past consumption of tea, carbonated beverages, beer, or spirits; and an association with coffee consumption was inconsistent. A strong association between pancreas cancer and history of subtotal gastrectomy at any past time could not be explained by chance or any other factor. Pancreas cancer patients had experienced fewer allergies of any kind.
From college data on 50,000 male former students, the records of 126 men who died of pancreatic cancer in a 16-50 yr follow-up period were compared with those of 504 surviving classmates with respect to physical and social characteristics. Return mail questionnaires received from 30,000 surviving alumni in 1962 or 1966 also were reviewed for characteristics that might predict altered risk of pancreatic cancer. Strong positive associations were found for cigarette smoking as reported both during college (p less than 0.001) and at time of questionnaire return (p = 0.03). Smoking 10 or more cigarettes per day during college corresponded to a relative risk of 2.6 with 95% confidence limits 1.5 to 4.6, and a positive smoking history at questionnaire return yielded a relative risk of 2.4 (1.1-5.1). No association was found for collegiate coffee drinking, either before or after adjustment for cigarette smoking. The relative risk for coffee drinking adjusted for smoking was 1.1 (0.7-1.8). In contrast, collegiate tea consumption was associated with a reduction in pancreatic cancer risk. The relative risk for tea drinking adjusted for smoking was 0.5 (0.3-0.9). Men who at college physical examination complained of occasional abdominal pain or discomfort had increased relative risk of pancreatic cancer (3.1 : 1.1-9.0) in the follow-up period.
Risk factors for pancreatic cancer were examined in a cohort study of 13,979 residents of a retirement community. After 9 years of follow-up, 65 incident cases of pancreatic cancer were identified. An increased risk of pancreatic cancer was associated with a history of diabetes and cholecystectomy. Higher intake of vegetables, fruits, dietary beta-carotene, and vitamin C were each associated with a reduced risk of pancreatic cancer, although none of these associations was statistically significant. Risk of pancreatic cancer decreased with increasing tea consumption but was unrelated to coffee consumption. No strong or consistent association was seen between either smoking or alcohol consumption and risk of pancreatic cancer, but a consistent and significant increase in risk followed cholecystectomy.
A population-based, case-control study of pancreas cancer was undertaken in Opole, Poland, within the framework of the SEARCH Programme of the International Agency for Research on Cancer: this is the first aetiological study of pancreas cancer reported from Poland where the reported mortality rate has doubled since 1963. This study of pancreas cancer has provided some further supporting evidence of an association between increased pancreas risk with increasing levels of cigarette smoking. The risk rose with increasing lifetime cigarette consumption with a trend which was weakly significant (p = 0.061). Findings regarding lifetime tea and coffee consumption were not consistent with intake of either beverage increasing the risk of this disease. There was a strongly significant trend of decreasing risk with increasing lifetime consumption of tea (p < 0.001), which was also apparent when the analysis was restricted to subjects who were interviewed directly. For coffee consumption, which is low in Poland, there was also a negative association apparent in the data which was not statistically significant among the sub-set of subjects who were directly interviewed. The findings regarding alcoholic beverages were overall null, although the weakly positive trend in risk with spirits consumption (p = 0.71) may deserve further investigation in view of the special nature of the source of spirits (vodka) in Poland.
The effect of green tea drinking in reducing human cancer risk is unclear, though a protective effect has been reported in numerous animal studies and several epidemiologic investigations. Herein the hypothesis that green tea consumption may reduce the risk of cancers of the colon, rectum and pancreas is examined in a large population-based case-control study conducted in Shanghai, China. Newly diagnosed cancer cases (931 colon, 884 rectum and 451 pancreas) during 1990-1993 among residents 30-74 years of age were included. Controls (n = 1,552) were selected among Shanghai residents and frequency-matched to cases by gender and age. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) of each cancer associated with green tea consumption were derived after adjustment for age, income, education and cigarette smoking. Additional adjustment for dietary items and body size was found to have minimal impact. An inverse association with each cancer was observed with increasing amount of green tea consumption, with the strongest trends for rectal and pancreatic cancers. For men, compared with non-regular tea drinkers, ORs among those in the highest tea consumption category (> or = 300 g/month) were 0.82 for colon cancer, 0.72 for rectal cancer and 0.63 for pancreatic cancer, with p values for trend being 0.38, 0.04 and 0.04, respectively. For women, the respective ORs for the highest consumption category (> or = 200 g/month) were 0.67, 0.57 and 0.53, with the respective p values for trend being 0.07, 0.001 and 0.008. Our findings provide further evidence that green tea drinking may lower the risk of colorectal and pancreatic cancers.
Epidemiologic studies have shown a lower risk of gastrointestinal cancer in green tea drinkers. In the present study, the inhibitory effect of green tea extract (GTE) on the process of pancreatic carcinogenesis induced by N-nitrosobis-(2-oxypropyl)amine (BOP) and on tumor promotion after transplantation of N-nitrosobis-(2-hydroxypropyl)amine (BHP)-induced pancreatic cancer were investigated in hamsters. In the first experiment, shortly after the initiation of pancreatic carcinogenesis by BOP, the animals in the GTE group were given GTE (0.5 mg/L) in their drinking water and the control group was given tap water. All animals were sacrificed 24 weeks later. There were no significant differences in body weight, water intake, or food consumption between the two groups during the experiments. GTE consumption was approximately 1.25 mg/day/100 g body weight during this experiment. Seven of the 13 hamsters (54%) in the control group were found to have pancreatic tumors, versus six of the 18 hamsters (33%) in the GTE group. The average number of tumors in the control group was 1.0/hamster, compared with 0.5/hamster in the GTE group. The overall incidence of macroscopic pancreatic tumors in the GTE group was about half that in the control group. The incidence of pancreatic cancer was 54% (12/13) in the control group and 44% (8/18) in the GTE group. The number of pancreatic cancers, including invasive carcinoma and carcinoma in situ, in the GTE group was 0.88/hamster, significantly lower than in the control group (1.68/hamster) (p < 0.05). The incidence of atypical ductal hyperplasia, which is thought to be an early pancreatic cancer, was also significantly lower in the GTE group than in the control group (1.50/hamster vs. 4.65/hamster) (p < 0.05). In the second experiment, 1-mm3 pieces of BHP-induced pancreatic cancer were transplanted into the back of hamsters. The control group (N = 16) was maintained on the basal diet and tap water throughout the experiment, and the GTE group (N = 16) was also maintained on the basal diet and tap water for the first 3 weeks after transplantation, when successful transplantation was confirmed and, thereafter, given tap water containing GTE (0.5 mg/L) for an additional 12 weeks. Tumor growth was similar in both groups until 11 weeks after transplantation, but inhibition of tumor growth became apparent after 11 weeks in the GTE group. At 13 weeks, the average tumor volume in the GTE group was 1.01 +/- 0.11 x 104 mm3, significantly smaller than that in the control group (1.98 +/- 0.37 x 104 mm3) (p < 0.05). The results demonstrated that GTE has an inhibitory effect on the process of pancreatic carcinogenesis and on tumor promotion of transplanted pancreatic cancer. These results suggest that GTE may come to serve as a chemopreventive and chemotherapeutic agent for pancreatic cancer.
To assess the relationship of smoking and coffee, tea, and alcohol intake to the risk of cancer of the exocrine pancreas, analyses were performed using data from a prospective cohort study of 33,976 postmenopausal Iowa women who responded to a mailed questionnaire in 1986 and were followed through 1994 for cancer incidence and total mortality. At baseline, information on cigarette smoking, consumption of tea, coffee, and alcoholic beverages, and other dietary and lifestyle factors was obtained. Age-adjusted relative risks of pancreatic cancer (n = 66 cases) showed a dose-response association with smoking. Those with fewer than 20 pack-years and those with 20 or more pack-years of smoking exposure were 1.14 (95% confidence interval, 0.53-2.45) and 1.92 (95% confidence interval, 1.12-2.30) times more likely, respectively, to develop pancreatic cancer than were nonsmokers. Current smokers were twice as likely as were nonsmokers to develop pancreatic cancer. Relative risks of pancreatic cancer increased with the amount of alcohol consumed (Ptrend = 0.11) after adjustment for age, smoking status, and pack-years of smoking. Relative risks of pancreatic cancer according to alcoholic beverage intake were as strong among never-smokers as they were in the total cohort. After the data were adjusted for age, smoking status, and pack-years of smoking, there was a statistically significant 2-fold (95% confidence interval, 1.08-4.30) elevated risk of pancreatic cancer for those who drank > 17.5 cups of coffee per week, compared to those who consumed < 7 cups/week; among never-smokers, the relative risks across coffee intake categories were still positive but were attenuated somewhat (P trend = 0.17). Tea intake was not related to cancer incidence. In summary, these findings provide evidence of an association of both alcoholic beverage and coffee consumption with pancreatic cancer incidence that is independent of age and cigarette smoking.
The effects of alpha-carotene, beta-carotene, palm carotene, and green tea polyphenols (GTP) on the progression stage of pancreatic carcinogenesis after rapid production of ductal lesions were studied in Syrian hamsters. Dose threshold inhibitory effects were noted for beta-carotene, 25 ppm, and palm carotene, 40 ppm, which includes 24 ppm beta-carotene reducing the numbers of putative preneoplastic lesions of duct epithelial hyperplasia and atypical hyperplasia, as well as carcinoma in situ and invasive carcinomas. GTP at doses of 500 and 5000 ppm, but not 100 ppm, also significantly decreased the numbers of hyperplasia and total duct lesions. Combined administration of 40 ppm palm carotene, and 50 ppm GTP similarly inhibited the lesion development. Alpha-carotene, however, did not affect pancreatic carcinogenesis. The results suggest that chemopreventive effects are exerted by beta-carotene and GTP above critical doses and that combined administration of palm carotene and GTP might be a candidate chemoprevention strategy for pancreatic cancer in humans.
We conducted a systematic meta-analysis of observational studies on cigarette smoking and cancer from 1961 to 2003. The aim was to quantify the risk for 13 cancer sites, recognized to be related to tobacco smoking by the International Agency for Research on Cancer (IARC), and to analyze the risk variation for each site in a systematic manner. We extracted data from 254 reports published between 1961 and 2003 (177 case-control studies, 75 cohorts and 2 nested case-control studies) included in the 2004 IARC Monograph on Tobacco Smoke and Involuntary Smoking. The analyses were carried out on 216 studies with reported estimates for 'current' and/or 'former' smokers. We performed sensitivity analysis, and looked for publication and other types of bias. Lung (RR = 8.96; 95% CI: 6.73-12.11), laryngeal (RR = 6.98; 95% CI: 3.14-15.52) and pharyngeal (RR = 6.76; 95% CI: 2.86-15.98) cancers presented the highest relative risks (RRs) for current smokers, followed by upper digestive tract (RR = 3.57; 95% CI: 2.63-4.84) and oral (RR = 3.43; 95% CI: 2.37-4.94) cancers. As expected, pooled RRs for respiratory cancers were greater than the pooled estimates for other sites. The analysis of heterogeneity showed that study type, gender and adjustment for confounding factors significantly influence the RRs estimates and the reliability of the studies.
Pancreatic cancer is one of the most aggressive and treatment-refractory malignancies in humans. The most effective means of reducing pancreatic cancer mortality may be primary prevention. Although laboratory studies have demonstrated that green tea possesses anticancer activities, results from epidemiological studies have failed to show a consistent cancer-preventive effect. In addition, there is a lingering concern that coffee mighty increase the risk of pancreatic cancer although the most recent epidemiological studies showed no overall association between coffee and risk. Here, we examined the association between the drinking of green tea or coffee and the risk of pancreatic cancer in a large population-based cohort study in Japan (JPHC study). In total, 102 137 participants were followed for an average of 11 years through to the end of 2003. A total of 233 incident cases of pancreatic cancer were identified among 1 116 945 person-years of follow-up. Overall, the risk of pancreatic cancer was not associated with either green tea or coffee intake in our population, although a reduced risk was apparent among men who drank at least three cups of coffee per day compared with those who did not drink any or only rarely drank coffee. In conclusion, our findings support the idea that green tea or coffee consumption does not have a substantial impact on pancreatic cancer risk in general.
Green tea polyphenols have been shown to inhibit tumor growth in animal and in vitro studies. We examined the relationship between green tea consumption and the risk of death from pancreatic cancer in a large Japanese cohort.
At baseline (1988-1990), study participants reported the frequency and amount of green tea consumption during the past year. They were followed-up for mortality until December 31, 2003. Relative risk and 95% confidence intervals were calculated from Cox proportional hazard models.
During an average follow-up of 13 years, we observed 292 pancreatic cancer deaths. In men and women combined, the relative risk was 1.23 (95% confidence interval, 0.84-1.80) for participants who consumed 7 or more cups of green tea per day as compared with those who consumed less than 1 cup per day, after adjustment for potential confounding factors. No significant trend in risk reduction was noted, with increasing consumption of green tea. We found no inverse association between cups of green tea consumed per day and the risk of pancreatic cancer in either men or women.
Our findings do not support the hypothesis that green tea consumption is associated with decreased risk of pancreatic cancer in humans.
Cancer incidence, mortality and survival rates in urban Shanghai 1973-2000. Shanghai: Second Military Medical University Press
- Y-T Gao
- W Lu
Gao, Y-T.; Lu, W., editors. Cancer incidence, mortality and survival rates in urban Shanghai 1973-2000. Shanghai: Second Military Medical University Press; 2007. p. 69-124.(Chinese)