The scientific literature has reported an inverse association between broccoli consumption and the risk of suffering from several types of cancer; however, the results were not entirely consistent across studies. A systematic review and meta-analysis of observational studies were conducted to determine the association between broccoli consumption and cancer risk with the aim of clarifying the beneficial biological effects of broccoli consumption on cancer.

PubMed/MEDLINE, Web of Science, Scopus, Cochrane Library (CENTRAL), and Epistemonikos databases were searched to identify all published papers that evaluate the impact of broccoli consumption on the risk of cancer. Citation chasing of included studies was conducted as a complementary search strategy. The risk of bias in individual studies was assessed using the Newcastle-Ottawa Scale. A random-effects model meta-analysis was employed to quantitatively synthesize results, with the I2 index used to assess heterogeneity.

Twenty-three case-control studies (n = 12,929 cases and 18,363 controls; n = 31,292 individuals) and 12 cohort studies (n = 699,482 individuals) were included in the meta-analysis. The results suggest an inverse association between broccoli consumption and the risk of cancer both in case-control studies (OR: 0.64, 95% CI from 0.58 to 0.70, p < 0.001; Q = 35.97, p = 0.072, I2 = 30.49%-moderate heterogeneity; τ2 = 0.016) and cohort studies (RR: 0.89, 95% CI from 0.82 to 0.96, p = 0.003; Q = 13.51, p = 0.333, I2 = 11.21%-low heterogeneity; τ2 = 0.002). Subgroup analysis suggested a potential benefit of broccoli consumption in site-specific cancers only in case-control studies.

In summary, the findings indicate that individuals suffering from some type of cancer consumed less broccoli, suggesting a protective biological effect of broccoli on cancer. More studies, especially cohort studies, are necessary to clarify the possible beneficial effect of broccoli on several types of cancer.

Colon cancer incidence is associated with a high-fat diet. Such a diet is linked to elevated levels of bile acids in the gastrointestinal system and the circulation. Secondary bile acids are produced by microorganisms present at high concentrations in the colon. Recent prospective studies and a retrospective study in humans associate high circulating blood levels of secondary bile acids with increased risk of colon cancer. Feeding mice a diet containing a secondary bile acid, so their feces have the bile acid at a level comparable to that in the feces of humans on a high-fat diet, also causes colon cancer in the mice. Studies using human cells grown in culture illuminate some mechanisms by which bile acids cause cancer. In human cells, bile acids cause oxidative stress leading to oxidative DNA damage. Increased DNA damage increases the occurrence of mutations and epimutations, some of which provide a cellular growth advantage such as apoptosis resistance. Cells with such mutations/epimutations increase by natural selection. Apoptosis, or programmed cell death, is a beneficial process that eliminates cells with unrepaired DNA damage, whereas apoptosis-resistant cells are able to survive DNA damage using inaccurate repair processes. This results in apoptosis-resistant cells having more frequent mutations/epimutations, some of which are carcinogenic. The experiments on cultured human cells have provided a basis for understanding at the molecular level the human studies that recently reported an association of bile acids with colon cancer, and the mouse studies showing directly that bile acids cause colon cancer. Similar, but more limited, findings of an association of dietary bile acids with other cancers of the gastrointestinal system suggest that understanding the role of bile acids in colon carcinogenesis may contribute to understanding carcinogenesis in other organs.

Essential elements in serum are related to specific changes in food groups intake.

To address the effect of 2-year food intake changes in an intervention study on serum concentrations of magnesium, zinc, copper, and selenium.

Two hundred thirty-one participants, a subgroup of the Dietary Intervention Randomized Control Trial (DIRECT) study (age = 52 years; body mass index = 32.8 kg/m(2); 85% males) randomized to low-fat, Mediterranean, or low-carbohydrate diets in a 2-year dietary intervention trial were followed for serum concentrations determined using inductively coupled plasma-mass spectrometry. Changes in the intake of 11 food groups were evaluated by food frequency questionnaires.

Using multivariate regression models, adjusted for age, sex, baseline body weight (kg), and changes in intakes of 11 food groups (g/d), at 12 months, serum element elevations were observed mainly in the low-carbohydrate group: selenium, by increasing consumption of fats and oils (β = 0.415, p = 0.009) and legumes (β = 0.183, p = 0.010) and decreasing fruit intake (β = -0.438, p = 0.030); copper, by increasing consumption of legumes (β = 0.453, p = 0.018) and dairy products (β = 0.320, p = 0.039); magnesium by increasing fish consumption (β = 0.374, p = 0.042) in the low-carbohydrate group and in the entire study population (β = 0.237, p = 0.016); and zinc exclusively in the low-fat group by decreasing consumption of fats and oils (β = -0.575, p = 0.022). At 24 months, serum elements were elevated mainly in the low-fat diet group, mostly by decreasing intake of snacks, sweets, and cakes: zinc (β = -0.570, p = 0.027), copper (β = -0.649, p = 0.012), and selenium (β = -0.943, p < 0.001). Also in this group, magnesium levels were elevated by increasing vegetable intake (β = 0.395, p = 0.041), copper by increasing fruit intake (β = 0.375, p = 0.025), and selenium by increasing consumption of bread, pasta, and cereals (β = 0.751, p = 0.011). The entire group, further adjusted to assigned diet type, increased selenium (β = 0.294, p = 0.004) and copper (β = 0.220, p = 0.038) by increasing consumption of bread, pasta, and cereals; selenium level was also predicted by decreasing consumption of snacks, sweets, and cakes (β = -0.256, p = 0.014). Introducing energy expenditure, expressed in metabolic equivalents (MET = 1 kcal·kg(-1)·h(-1)), as an additional variable emphasized the negative effect of sweets and cakes on increasing serum concentrations of zinc, copper, and selenium after 24 months (β = -0.549, p = 0.021; β = -0.669, p = 0.012; β = -0.982, p < 0.001, respectively), especially in the low-fat diet group. No significant associations between changes in food groups intake and the 4 elements were found in the Mediterranean diet group.

During this 2-year intervention, serum concentrations of 4 essential elements were associated with a diversity of food group intake patterns. Comprehensive predictors for elevating zinc, copper, and selenium in serum included decreasing consumption of sweets and cakes while increasing consumption of bread, cereals, and pasta.

Allyl isothiocyanate (AITC) is a dietary component with possible anticancer effects, though much information about AITC and cancer has been obtained from cell studies. To investigate the effect of AITC on DNA integrity in vivo, a crossover study was conducted. Adults (n=46) consumed AITC, AITC-rich vegetables [mustard and cabbage (M/C)] or a control treatment with a controlled diet for 10 days each. On day 11, volunteers provided blood and urine before and after consuming treatments. Volunteers were characterized for genotype for GSTM1 and GSTT1 (glutathione S-transferases) and XPD (DNA repair). DNA integrity in peripheral blood mononuclear cells was assessed by single-cell gel electrophoresis. Urine was analyzed for 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and creatinine. Ten-day intake of neither AITC nor M/C resulted in statistically significant differences in DNA strand breaks [least squares mean (LSmean) % DNA in tail±S.E.M.: 4.8±0.6 for control, 5.7±0.7 for AITC, 5.3±0.6 for M/C] or urinary 8-oxodG (LSmean μg 8-oxodG/g creatinine±S.E.M.: 2.95±0.09 for control, 2.88±0.09 for AITC, 3.06±0.09 for M/C). Both AITC and M/C increased DNA strand breaks 3 h postconsumption (LSmean % DNA in tail±S.E.M.: 3.2±0.7 for control, 8.3±1.7 for AITC, 8.0±1.7 for M/C), and this difference disappeared at 6 h (4.2±0.9 for control, 5.7±1.2 for AITC, 5.5±1.2 for M/C). Genotypes for GSTM1, GSTT1 and XPD were not associated with treatment effects. In summary, DNA damage appeared to be induced in the short term by AITC and AITC-rich products, but that damage disappeared quickly, and neither AITC nor AITC-rich products affected DNA base excision repair.

Distinct weight loss dietary strategies are associated with changes in specific food groups.

To address the effect of changes in specific weight of food groups on weight loss in a 2-year low-fat, Mediterranean, low-carbohydrate intervention trial (DIRECT).

We assessed changes in the intake of 12 food groups among 322 participants (body mass index [BMI] = 31 kg/m(2); age = 52 years; 86% men), using a validated electronic food frequency questionnaire.

The weight of the 3592.9 ± 1558 (g/d ± SD) of baseline food consumed consisted mainly of liquids, excluding water (32.6% of total weight of food); vegetables (18.8%), fruits (17.7%), dairy (9.0%), meat (7.7%), and bread/cereal/pasta/potatoes (7.1%). Participants significantly reduced food intake by 283.73 ± 1342 (g/d ± SD) at 6 months and by 963.36 ± 1869 (g/d ± SD) at 24 months (p < 0.05 as compared with baseline). Food weight changes were similar across diet groups (p = 0.366), whereas 6-month body weight loss was -4.6 ± 4.4 kg, -4.7 ± 4.9 kg, and -6.4 ± 6.6 kg for low-fat, Mediterranean, and low-carbohydrate groups, respectively; p < 0.026). In multivariate regression models, adjusted for age, sex, baseline body weight, and changes in weight intake of 12 food groups (g/d), independent dietary predictors (standardized-β) at 6 months (rapid weight loss phase) were as follows: decreased consumption of sweets and cakes (β = 0.493; p = 0.008) in the low-fat group, tendency toward increased crude legumes (β = -0.196; p = 0.061) in the Mediterranean group, and increased vegetable intake (β = -0.249; p = 0.018) in the low-carbohydrate diet group. In the entire group, in models further adjusted for diet type, leading predictors for rapid weight loss phase were as follows: increased vegetables by ~140 g/d (β = -0.116; p = 0.045) and decreased intake of sweets and cakes by ~30 g/d (β = 0.162; p = 0.010). Universal predictors for 2-year successful weight loss in the entire group were as follows: increased intake of vegetables (β = -0.192; p = 0.007) and meat (β = -0.146; p = 0.026) and decreased intake of eggs (β = 0.187; p = 0.003), processed legumes (β = 0.195; p = 0.002), and beverages (β = 0.135; p = 0.032).

Two-year weight loss is associated with a decrease of ~1 kg of total food consumed and may be achieved by a variety of changes in specific food groups within different diet strategies. Universal predictors of successful weight loss in the rapid weight loss phase across all diet strategies are increasing the weight of intake of vegetables and decreasing the weight of intake of sweets and cakes.

The modifying potential on tumor development of arachidonate-enriched triglyceride oil (ARA-oil) containing approximately 40% arachidonic acid was investigated in a medium-term multi-organ carcinogenesis bioassay using male and female F344 rats. The animals were sequentially given five carcinogens with different target sites in the first 4 weeks, and then administered ARA-oil for 24 weeks at dietary levels of 0% (control), 1.25%, 2.5% or 5.0%. No statistically significant differences in incidences and multiplicities of hyperplastic and neoplastic lesions were showed in the large intestine in either sex. In the liver, kidney, and lung in both sexes, and the mammary gland and uterus in females, tumor promoting potential was not evident with ARA-oil treatment. ARA-oil did not affect the quantitative data for glutathione S-transferase placental form positive foci of the liver. Increased induction of hyperplastic or neoplastic lesions in the urinary bladder and thyroid in ARA-oil-treated groups was without dose dependence. In addition, a second experiment with ARA-oil only administration for 8-week revealed no effects on cellular proliferation in the urinary bladder or thyroid in either sex. These results indicate that ARA-oil has no tumor promoting potential in any organs or tissues initiated with the five carcinogens applied in the present study.

Although traditionally cancer has been fought with the usual armamentarium of chemotherapy and high doses of directed radiation, lately there has been more attention devoted to combating cancer through nutritive means. In particular, certain phytochemicals including some vitamins, some minerals and a wide range of other bioactive nutrients have been found useful in the physiological battle against cancer.

The objective of this article is to determine which vitamins, minerals and bioactive nutrients may be useful in combating cancer and to give therapeutic dosages of such when known.

The scientific literature is replete with research documenting the link between certain nutritional protocols and inhibition or protection against the disease of cancer. From the landmark article entitled The Causes of Cancer by Richard Doll and Richard Peto which was first commissioned as a report to the Office of Technology Assessment of the United States Congress to the American Cancer Societys Advisory Committee Guidelines on Diet, Nutrition and Cancer Prevention: Reducing the Risk of Cancer with Health Food Choices and Physical Activity, the nutritional literature continues to provide the necessary link for the clinician to justifiably advise patients regarding proper dietary habits in order reduce the patients risk of cancer.

Although there has been much research regarding the relationship between vitamins, minerals and other bioactive phytonutrients and cancer and protection against cancer, not all of the literature supports a strong and convincing link between the nutrient and cancer protection. This article differentiates the convincing evidence vs. the probable and the possible evidence of the link between the nutrient and its inhibitive effect on cancer.

Certain vitamins, minerals and bioactive phytonutrients can be used as a first line of therapeutic defense against cancer before chemotherapy and radiation treatment is commenced.

High dietary fat causes increased bile acid secretion into the gastrointestinal tract and is associated with colon cancer. Since the bile acid deoxycholic acid (DOC) is suggested to be important in colon cancer etiology, this study investigated whether DOC, at a high physiologic level, could be a colon carcinogen. Addition of 0.2% DOC for 8-10 months to the diet of 18 wild-type mice induced colonic tumors in 17 mice, including 10 with cancers. Addition of the antioxidant chlorogenic acid at 0.007% to the DOC-supplemented diet significantly reduced tumor formation. These results indicate that a high fat diet in humans, associated with increased risk of colon cancer, may have its carcinogenic potential mediated through the action of bile acids, and that some dietary anti-oxidants may ameliorate this carcinogenicity.

Colorectal cancer has been strongly associated with a Western lifestyle. In the past several decades, much has been learned about the dietary, lifestyle, and medication risk factors for this malignancy. Although there is controversy about the role of specific nutritional factors, consideration of dietary pattern as a whole appears useful for formulating recommendations. For example, several studies have shown that high intake of red and processed meats, highly refined grains and starches, and sugars is related to increased risk of colorectal cancer. Replacing these factors with poultry, fish, and plant sources as the primary source of protein; unsaturated fats as the primary source of fat; and unrefined grains, legumes and fruits as the primary source of carbohydrates is likely to lower risk of colorectal cancer. Although a role for supplements, including vitamin D, folate, and vitamin B6, remains uncertain, calcium supplementation is likely to be at least modestly beneficial. With respect to lifestyle, compelling evidence indicates that avoidance of smoking and heavy alcohol use, prevention of weight gain, and maintenance of a reasonable level of physical activity are associated with markedly lower risks of colorectal cancer. Medications such as aspirin and nonsteroidal anti-inflammatory drugs and postmenopausal hormones for women are associated with substantial reductions in colorectal cancer risk, though their utility is affected by associated risks. Taken together, modifications in diet and lifestyle should substantially reduce the risk of colorectal cancer and could complement screening in reducing colorectal cancer incidence.

Enviromental factors have been consistently associated with colon cancer risk. In particular, consumption of Western-style diet including red meat is the most widely accepted etiologic risk factor. It has been reported that dietary factors change the proportion of intestinal flora, and it also affects the composition of fecal bile acids and the intestinal activity of some mutagens. In addition, it was suggested that modulating the composition of intestinal flora may reduce the occurrence of colorectal cancer. In this review, we present the clinical studies on the association between intestinal flora and the risk of colorectal cancer that have been carried out to date. The clinical studies of intestinal bacteria related to colorectal cancer risk have not shown consistent results so far, compared with the accomplishments of some basic studies. On the other hand, it was suggested in some clinical studies that lactic acid bacteria reduce the occurrence of colorectal cancer.

We consider some of the earlier work and some recent results on diet and cancer (since the 2007 WCRF/AICR report on Diet and Cancer), discuss challenges facing nutritional cancer epidemiology, and consider the field from the perspective of the need to apply what we know in cancer control. We highlight 2 current difficulties; first, we are uncertain on the stage of carcinogenesis on which many nutritional factors act, second, we often do not know what dose of a nutritional factor is needed to achieve its expected protective effect in humans. Part of the difficulty is the measurement error associated with food frequency questionnaires. Calibration studies (as in the European Prospective Investigation on diet and Cancer) have helped to reduce this, and pooled studies have helped to clarify associations. However, there is too little work on new biomarkers of nutrition; with the new techniques available (especially proteomics, and metabolomics) it should be possible to identify more and better biomarkers that could be used in repeated blood or urine samples and give very good information on diet. In cancer control we need to determine how to reduce the prevalence of obesity and increase physical activity in populations, not whether they are causal factors. This could be achieved by community-based interventions linked to some of the new cohort studies being initiated. We conclude we have reached the stage in nutritional cancer epidemiology where we need to concentrate more on applying the lessons we have learnt, than in seeking new aetiological associations.

The modifying potential of diacylglycerol (DAG) oil on tumor development was investigated in a medium-term multi-organ carcinogenesis bioassay. DAG oil is a cooking oil that contains >80% diglycerides, <20% triglycerides and <5% monoglycerides. Male 6-week-old F344 rats (20 in each group) were sequentially treated with five carcinogens for initiation in different organ target sites for 4 weeks (DMBDD treatment), and then administered DAG oil at dietary levels of 0% (control), 1.375%, 2.75% or 5.5% [triacylglycerol (TGs), with the same fatty acid composition as DAG oil were also added at dietary levels of 5.5%, 4.125%, 2.75% and 0%, respectively, to maintain the same lipid level], or 5.5% high linoleic acid TG (HLTG), 5.5% high oleic acid TG (HOTG), or 5.5% medium-chain TG (MCTG) (as reference substances, mostly consisting of triacylglycerols) admixed into AIN-93G semi-synthetic diet, for an additional 24 weeks. Controls received standard diet without any supplementation as non-treated control. All animals were killed at the end of week 28, and the major organs were carefully examined for preneoplastic and neoplastic lesions. No DAG oil treatment-related changes were noted in survival, general conditions, body weights, food consumption and organ weights. Upon quantitative analysis of glutathione S-transferase placental form (GST-P) positive foci of the liver, DAG oil was not found to exert any effects. The incidence of colon adenomas was significantly increased in rats given 1.375% DAG oil, but not 2.75% and 5.5% DAG oil, when compared to the control (5.5% TG group) value. Furthermore, incidences and multiplicity of hyperplasias and adenomas and/or adenocarcinomas were comparable across all DAG oil-treated groups. In contrast, incidences of colon adenomas and/or adenocarcinomas were significantly increased in rats given 5.5% HOTG, and adenomas with MCTG, but not 5.5% HLTG, as compared to the 5.5% TG value. Preneoplastic and neoplastic lesions induced by DMBDD treatment in various organs other than the large intestine were comparable in all cases. Thus, the current results indicate that DAG oil may not exert modifying potential on tumor development, even in the colon because of the lack of dose-dependence. DAG oil was equivalent to HOTG (standard cocking oil composed of naturally occurring fatty acids), with regard to colon tumor development. Further dose-response study concerning HOTG may be needed to confirm whether the enhancing effect of large intestine carcinogenesis exert or not.

Dietary peroxisome proliferator-activated receptor (PPAR)gamma ligands, linoleic acid (LA) and conjugated linoleic acid (CLA), showed anticancer effects in colorectal carcinoma cells. LA is metabolized by two pathways. Cyclooxygenase (COX)-2 produces procarcinogenic prostaglandin E2, whereas 15-lipoxygenase (LOX)-1 produces PPARgamma ligands. The 15LOX-1 pathway, which is dominant in colorectal adenomas, was downregulated and inversely COX-2 was upregulated in colorectal cancer. LA and CLA inhibited peritoneal metastasis of colorectal cancer cells in nude mice. The inhibitory effect was abrogated by PPARgamma antisense treatment. A continuous LA treatment provided cancer cells quiescence. These quiescent cells formed dormant nests in nude mice administrated LA. The quiescent and dormant cells showed downregulated PPARgamma and upregulated nucleostemin. Thus, short-term exposure to dietary PPARgamma ligands inhibits cancer metastasis, whereas consistent exposure to LA provides quiescent/dormant status with possible induction of cancer stem and/or progenitor phenotype. The complicated roles of dietary PPARgamma ligands are needed to examine further.

The association between diet and colorectal cancer has been studied in depth for many decades, with equivocal results. It has been hypothesized that cancers arising in the distal and proximal colon have different pathologies, and therefore different risk factors. As such, it is possible that diet-related factors might influence colorectal neoplasia differently depending on the subsite. Recent evidence indicates that women may be more likely to develop proximal cancers than men. Additionally, the link between certain dietary factors and colorectal neoplasia in women seems to vary by menopausal status. Given these observations, women may be affected differently than men by diet-related factors. The objective of this article was therefore to review the data for diet and colorectal adenomas and cancer, and then attempt to address the potential differences in the association of diet-related factors and colorectal neoplasia in men and women. For total energy intake, selenium, and fiber, it seems that there may be slightly stronger effects in men as compared with women, whereas calcium and folate seem to affect both sexes similarly. With regard to vitamin D and colorectal cancer, women may exhibit stronger associations than men. Perhaps the most evidence for a sex-specific effect is observed for obesity, where more substantial direct relationships between body size and colorectal neoplasia have been reported for men than for women. However, this observation may be influenced by the differential effects in women by menopausal status. Further research on sex-specific dietary effects is warranted.

Dairy food consumption has been inconsistently shown to protect against colorectal cancer (CRC) in case-based studies, and no clear benefits against recurrent colonic polyps (CRP) have been reported. Based on population-based studies we have hypothesized that dairy food intake may have anti-CRC effects at both low intake lactase non-persistent (LNP) populations and at high intake lactase persistent (LP) subjects. We separately analyse existing case-based studies and divide origins into high LNP (>or= 80% LNP prevalence), low LNP (prevalence <or= 20%) and mid LNP countries (21-79% prevalence), which coincide with low, high, and mid quantity dairy food intake regions, respectively. Odds ratios and relative risks (RR) of highest versus lowest dairy intake within each group are analyzed together for assessment of protection against CRC and CRP. Eighty studies met stipulated criteria. Thirteen analyzed the effect on recurrent polyps. Forest plots from 2 regions, high LNP (low dairy food intake) RR = 0.84 [95% confidence interval (CI) = 0.73-0.97) and low LNP (high dairy food intake) RR = 0.80 (95% CI = 0.73-0.88) demonstrated significant protection against CRC. In mixed LNP/LP populations (mid dairy food intake) nonsignificant protection was found RR = 0.92 (95% CI = 0.79-1.06). Similar regional analysis for CRP failed to show significant protective effect in any region. This meta-analysis supports that the highest level of dairy food consumption protects subjects in both high and low LNP regions but not in areas with significant mixed LNP/LP populations. In both groups, dairy foods had no effect on polyp formation, suggesting it may only protect against CRC at late stages of promotion. These results raise the possibility that LNP/LP status may be partly responsible for the discrepant results with respect to the relationship between dairy food consumption and CRC.

Alcohol consumption may be associated with risk of colorectal cancer (CRC), but the epidemiological evidence for an association with specific anatomical subsites, types of alcoholic beverages and current vs. lifetime alcohol intake is inconsistent. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 478,732 study subjects free of cancer at enrolment between 1992 and 2000 were followed up for an average of 6.2 years, during which 1,833 CRC cases were observed. Detailed information on consumption of alcoholic beverages at baseline (all cases) and during lifetime (1,447 CRC cases, 69% of the cohort) was collected from questionnaires. Cox proportional hazard models were used to examine the alcohol-CRC association. After adjustment for potential confounding factors, lifetime alcohol intake was significantly positively associated to CRC risk (hazard ratio, HR=1.08, 95%CI=1.04-1.12 for 15 g/day increase), with higher cancer risks observed in the rectum (HR=1.12, 95%CI=1.06-1.18) than distal colon (HR=1.08, 95%CI=1.01-1.16), and proximal colon (HR=1.02, 95%CI=0.92-1.12). Similar results were observed for baseline alcohol intake. When assessed by alcoholic beverages at baseline, the CRC risk for beer (HR=1.38, 95%CI=1.08-1.77 for 20-39.9 vs. 0.1-2.9 g/day) was higher than wine (HR=1.21, 95%CI=1.02-1.44), although the two risk estimates were not significantly different from each other. Higher HRs for baseline alcohol were observed for low levels of folate intake (1.13, 95%CI=1.06-1.20 for 15 g/day increase) compared to high folate intake (1.03, 95%CI=0.98-1.09). In this large European cohort, both lifetime and baseline alcohol consumption increase colon and rectum cancer risk, with more apparent risk increases for alcohol intakes greater than 30 g/day.

To evaluate the antioxidant and phase II detoxification enzyme inducing ability of green leaf vegetables consumed in Asia.

The antioxidant properties of six commonly consumed Asian vegetables were determined using the ABTS, DPPH, deoxyribose, PR bleaching and iron- ascorbate induced lipid peroxidation assay. Induce of phase II detoxification enzymes was also determined for each respective vegetable extract. Protection against authentic ONOO- and HOCl mediated cytotoxicity in human colon HCT116 cells was determined using the MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide) viability assay.

All of the extracts derived from green leaf vegetables exhibited antioxidant properties, while also having cytoprotective effects against ONOO- and HOCl mediated cytotoxicity. In addition, evaluation of the phase II enzyme inducing ability of each extract, as assessed by quinone reductase and glutathione-S-transferase activities, showed significant variation between the vegetables analyzed.

Green leaf vegetables are potential sources of antioxidants and phase II detoxification enzyme inducers in the Asian diet. It is likely that consumption of such vegetables is a major source of beneficial phytochemical constituents that may protect against colonic damage.

The effect of linoleic acid (LA) on growth and transformation of IEC6 intestinal cells was examined. IEC6 cells expressed mRNAs of 15-lipooxygenase (LOX15) and peroxisome proliferator-activated receptor (PPAR)gamma but not COX-2. Cell growth was suppressed by LA in a dose-dependent manner in IEC6 cells. Three-week treatment with LA provided IEC6 cells a quiescent state. LA-induced growth inhibition was abrogated by exposure to antisense S-oligodeoxynucleotides (S-ODNs) for LOX15 and/or PPARgamma. In an in vitro carcinogenesis model, IEC6 cells, which had confirmed CYP2E1 expression and activity, were continuously treated with AOM and/or LA for 40 weeks. DNA injury in AOM-treated cells was suppressed to the control level by concurrent LA treatment. Colony formation of AOM-treated cells in soft agar was suppressed by treatment with LA, which was reversed by exposure to antisense S-ODNs for LOX15 and/or PPARgamma. AOM-treated IEC6 cells formed s.c. tumors in 9 of 12 mice, whereas AOM+LA-treated cells formed no tumor. IEC6 cells showed no remarkable alteration of protein production by AOM treatment, whereas cells treated with AOM+LA showed decreased epidermal growth factor receptor (EGFR) and phospho-EGFR and increased BAX. These findings suggest that LA inhibited AOM-induced transformation of COX-2-negative IEC6 cells, which was possibly mediated with PPARgamma ligands generated by LOX15 from LA.

Bile acids were first proposed to be carcinogens in 1939 and 1940. On the basis of later work with rodent models, bile acids came to be regarded as cancer promoters rather than carcinogens. However, considerable indirect evidence, obtained more recently, supports the view that bile acids are carcinogens in humans. At least 15 reports, from 1980 through 2003, indicate that bile acids cause DNA damage. The mechanism is probably indirect, involving induction of oxidative stress and production of reactive oxygen species that then damage DNA. Repeated DNA damage likely increases the mutation rate, including the mutation rate of tumor suppressor genes and oncogenes. Additional reports, from 1994 through 2002, indicate that bile acids, at the increased concentrations accompanying a high fat diet, induce frequent apoptosis. Those cells within the exposed population with reduced apoptosis capability tend to survive and selectively proliferate. That bile acids cause DNA damage and may select for apoptosis-resistant cells (both leading to increased mutation), indicates that bile acids are likely carcinogens. In humans, an increased incidence of cancer of the laryngopharyngeal tract, esophagus, stomach, pancreas, the small intestine (near the Ampulla of Vater) and the colon are associated with high levels of bile acids. The much larger number of cell generations in the colonic (and, likely, other gastrointestinal) epithelia of humans compared to rodents may allow time for induction and selection of mutations leading to cancer in humans, although not in rodents.

The past two decades have provided a vast amount of literature related to the primary prevention of colorectal cancer. Large international variation in colorectal cancer incidence and mortality rates and the prominent increases in the incidence of colorectal cancer in groups that migrated from low- to high-incidence areas provided important evidence that lifestyle factors influence the development of this malignancy. Moreover, there is convincing evidence from epidemiological and experimental studies that dietary intake is an important etiological factor in colorectal neoplasia. Although the precise mechanisms have not been clarified, several lifestyle factors are likely to have a major impact on colorectal cancer development. Physical inactivity and to a lesser extent, excess body weight, are consistent risk factors for colon cancer. Exposure to tobacco products early in life is associated with a higher risk of developing colorectal neoplasia. Diet and nutritional factors are also clearly important. Diets high in red and processed meat increase risk. Excess alcohol consumption, probably in combination with a diet low in some micronutrients such as folate and methionine, appear to increase risk. There is also recent evidence supporting a protective effect of calcium and vitamin D in the etiology of colorectal neoplasia. The relationship between intake of dietary fiber and risk of colon cancer has been studied for three decades but the results are still inconclusive. However, some micronutrients or phytochemicals in fiber-rich foods may be important; folic acid is one such micronutrient that has been shown to protect against the development of colorectal neoplasia and is currently being studied in intervention trials of adenoma recurrence. The overwhelming evidence indicates that primary prevention of colon cancer is feasible. Continued focus on primary prevention of colorectal cancer, in combination with efforts aimed at screening and surveillance, will be vital in attaining the greatest possible progress against this complex, yet highly preventable disease.

Meat consumption, particularly of red and processed meat, is one of the most thoroughly studied dietary factors in relation to colon cancer. However, it is not clear whether meat, red meat, heterocyclic amines (HCA), or polycyclic aromatic hydrocarbons (PAH) are associated with the risk for rectal cancer. Rectal cancer cases (n = 952) and controls (n = 1205) from Utah and Northern California were recruited from a population-based case-control study between September 1997 and February 2002. Detailed in-person interviews regarding lifestyle, medical history, and diet were conducted. DNA was extracted from peripheral lymphocytes obtained from whole-blood samples, and glutathione S-transferase (GST)M1 enzyme and N-acetyl transferase (NAT)2 enzyme genotypes were assessed. Although energy and cholesterol intakes were higher among cases than controls, adjustment for confounders accounted for the differences. Increased consumption of well-done red meat [odds ratio (OR) 1.33 95% CI 0.98, 1.79] was associated with an (P = 0.04) increase in risk for rectal cancer among men. The mutagen index, calculated on the bases of reported amount, doneness, and method of cooking meat, was also positively but not significantly (P = 0.24) associated with risk of rectal cancer for men (OR 1.37 95% CI 0.98, 1.92). NAT2-imputed phenotype and GSTM1 did not consistently modify rectal cancer risk associated with meat intake. These data suggest that mutagens such as HCA that form when meat is cooked may be culpable substances in rectal cancer risk, not red meat itself.

Gastrointestinal cancer is one of the leading causes of cancer mortality in the world. Therefore, numerous efforts are being made to find chemoprotective substances able to reduce its incidence. Amongst these, green tea, one of the most popular beverages world-wide, has been reported to provide protective effects against gastrointestinal cancer.

To critically evaluate all epidemiological studies reporting an association between green tea consumption and a reduced risk of gastrointestinal cancer.

Epidemiological studies of green tea consumption in relation to gastrointestinal cancer or preneoplastic lesions were identified through computerized literature searches using the following databases: Medline (Pubmed), Embase, Amed, CISCOM, Phytobase and Cochrane Library. Only epidemiological studies indicating the type of tea (green tea) and the site of either cancer or precancerous lesions (stomach or intestine) were included. No language restrictions were imposed.

Twenty-one epidemiological investigations met our inclusion/exclusion criteria.

These studies seemed to suggest a protective effect of green tea on adenomatous polyps and chronic atrophic gastritis formations. By contrast, there was no clear epidemiological evidence to support the suggestion that green tea plays a role in the prevention of stomach and intestinal cancer.

Bromodichloromethane (BDCM) and tribromomethane given by corn oil gavage were previously found to induce neoplasia in the large intestine of rats. Our chronic bioassay of BDCM administered in drinking water failed to produce colon neoplasia in male F344/N rats. We recently reported that BDCM induces aberrant crypt foci (ACF), putative precursor lesions in the development of colon cancer, when included in the drinking water of male rats. To investigate whether ACF induced by BDCM could be promoted by corn oil (CO), male F344/N rats were exposed to 0.7 g BDCM/L in drinking water or 50 mg BDCM/kg body weight by oral gavage in CO. Animals exposed to drinking water, CO, or 15 mg/kg azoxymethane (AOM) (ip) constituted the negative, vehicle, and positive controls. After 26 wk, colons were examined for ACF. A significant decrease in water consumption was observed in both the positive controls and BDCM-treated animals; however, no difference was noted in final body weight. The administration of CO to AOM-exposed animals produced a significant increase in total ACF when compared to AOM alone. BDCM produced a significant increase in ACF when compared to control, but no difference was noticed between BDCM exposure by oral CO gavage and control. Additionally, no difference was noted between BDCM exposure by drinking water and by oral CO gavage. This study demonstrates that the formation of ACF is independent of the route of BDCM exposure (drinking water vs. oral corn oil gavage), with both routes producing similar ACF values of 1.33 +/- 0.49 and 1.5 +/- 0.51 ACF/colon.

Dietary energy restriction (DER) has long been known to strikingly inhibit carcinogenesis in many animal models. The animal data has been corroborated by recent and ongoing epidemiological studies demonstrating the importance of energy balance, physical exercise and obesity in human cancer. Dr. Edward Bresnick provided key insights into this important area of research and pivotal direction for the author's research while he served as Director of the Eppley Institute for Research in Cancer, Omaha, NE. These insights moved this research toward demonstrating that DER reduced the expression of key protein kinase C isoforms in mouse skin. More recent studies have uncovered downstream events that are inhibited by DER including blockage of tumor promoter activation of Raf-1, ERK 1,2 and AP-1 expression. Parallel studies have demonstrated the DER inhibition of these key cellular signaling events in mouse skin carcinogenesis are dependent upon an intact adrenal gland because adrenalectomized mice fed DER diet did not have reduced tumor burden or inhibited signaling and blocked AP-1 activation as was observed in DER mice with intact adrenal glands. In addition, the DER inhibition of tumorigenesis and AP-1 signaling was restored in adrenalectomized mice that were given corticosterone in the drinking water. This showed that in mice in the chemical carcinogenesis protocol glucocorticoid hormone plays a major role in mediating DER prevention of cancer. Studies are ongoing to further assess the mechanism of DER modulation of skin cancer by assessing impacts on transcriptional regulation and expression of genes that are critical in skin carcinogenesis.

This review presents a comprehensive, evenhanded evaluation of the evidence from experimental, in vitro and human studies associating environmental and therapeutic factors with risk of colorectal cancer. Life styles correlated with the greatest increase in colorectal cancer risk are the ones that typify a diet rich in fat and calories, alcohol drinking and tobacco smoking, and low intake of vegetable, fruits and fibers, referred to as a "western diet," as well as sedentary style (i.e., no- or low-exercise). This kind of life style has also been associated with other chronic diseases (other cancers, obesity, dyslipedemia, diabetes, hypertension cardiovascular, and hypertension). The evidence does not implicated red meat as a risk factor, and fiber has been shown to protect against colorectal adenomas and carcinomas. Calcium, vitamin D, folate, and some antioxidant vitamins and minerals (gamma-tocopherol and selenium) have protective effects, and daily exercise for > or =30 min results in a significant decrease in risk. Estrogen use (hormone replacement therapy) substantially reduces colorectal cancer risk in postmenopausal women. Nonsteroidal anti-inflammatory drugs (e.g., aspirin) in excessive doses is protective, especially in high risk populations, but the side effects of its use and cost incurred due to its continued intake over long periods must be carefully scrutinized before any recommendations are made for the general public.

Dietary heterocyclic aromatic amines (HCA) and polyunsaturated fatty acids (PUFA) are both believed to play a role in colon carcinogenesis, and are both substrate for the enzyme cyclooxygenase (COX). In HCA-7 cells, highly expressing isoform COX-2, we investigated the effects of PUFA on prostaglandin synthesis and DNA adduct formation by the HCA 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). Furthermore, we studied the role of COX, COX-2 in particular, and cytochrome P4501A2 (CYP1A2) by using the enzyme inhibitors indomethacin (IM), NS-398, and phenethyl isothiocyanate (PEITC), respectively. COX-mediated formation of prostaglandin E2 (PGE2) from linoleic acid (LA) showed that HCA-7 cells can convert LA into arachidonic acid (AA). Alternatively, eicosapentaenoic acid (EPA) was found to compete with AA for COX. Strongly decreased PGE2 levels by addition of IM demonstrated involvement of COX in PUFA metabolism. Both IM and NS-398 inhibited adduct formation by HCA to nearly the same extent, indicating involvement of COX-2 rather than COX-1, while CYP1A2 activity in HCA-7 cells was demonstrated by addition of PEITC. Overall, inhibiting effects were stronger for PhIP than for IQ. HCA-DNA adduct formation was stimulated by addition of PUFA, although high PUFA concentrations partly reduced this stimulating effect. Finally, similar effects for n-3 and n-6 fatty acids suggested that adduct formation may not be the crucial mechanism behind the differential effects of PUFA on colon carcinogenesis that have been described. These results show that COX, and COX-2 in particular, can play a substantial role in HCA activation, especially in extrahepatic tissues like the colon. Furthermore, the obvious interactions between PUFA and HCA in COX-2 expressing cancer cells may be important in modulating colorectal cancer risk.

Diets rich in fruit and vegetables have been recommended for preventing cancer. The evidence supporting this recommendation is based on observational studies, although results of several prospective studies have cast some doubts on whether fruit and vegetables are associated with cancer risk reduction.

We sought to summarize evidence from case-control and prospective studies on fruit and vegetable intake and cancer risk with a meta-analytic approach.

Published case-control and cohort studies that reported on total vegetable and fruit intake and risk of cancer of several sites were included. Relative risks were estimated by using linear logistic regression models.

Case-control studies overall support a significant reduction in the risks of cancers of the esophagus, lung, stomach, and colorectum associated with both fruit and vegetables; breast cancer is associated with vegetables but not with fruit; and bladder cancer is associated with fruit but not with vegetables. The overall relative risk estimates from cohort studies suggest a protective effect of both fruit and vegetables for most cancer sites considered, but the risk reduction is significant only for cancers of the lung and bladder and only for fruit.

Prospective studies provide weaker evidence than do case-control studies of the association of fruit and vegetable consumption with reduced cancer risk. The discrepancies may be related to recall and selection biases in case-control studies. In contrast, the association may have been underestimated in prospective studies because of the combined effects of imprecise dietary measurements and limited variability of dietary intakes within each cohort.

The relation between egg consumption and mortality from colon and rectal cancers remains unclear and was investigated in this study. Colon and rectal cancer mortality data, mostly around 1993-94 and egg consumption data in nine time periods (1964-94) in 34 countries were derived from World Health Organization and Food and Agriculture Organization, respectively. Egg consumption was significantly and positively correlated with mortality from colon and rectal cancers in both sexes in most of the nine time periods. The correlations were generally stronger for colon cancer (r = 0.39 to 0.63 in men and r = 0.33 to 0.65 in women) than for rectal cancer (r = 0.18 to 0.49 in men and r = 0.08 to 0.45 in women). After adjustment for confounding factors, egg consumption was still significantly and positively associated with mortality from colon cancer in the earliest five time periods (1964-84) (P = 0.046 to 0.017 in men and P = 0.034 to 0.014 in women) and rectal cancer in the latest five time periods except for the last time period (1982-91) (P = 0.046 to 0.024 in men and P = 0.045 to 0.026 in women). This study suggested that egg consumption was associated with an increased risk of colon and rectal cancers at the population level

Colorectal cancer is the second leading cause of cancer death in the United States, and the number of new cases annually is approximately equal for men and women. Several nutritional factors are likely to have a major influence on risk of this cancer. Physical inactivity and excessive adiposity, especially if centrally distributed, clearly increase the risk of colon cancer. Hyperinsulinemia may be an important underlying risk factor. In conjunction with obesity and physical inactivity, which induce a state of insulin resistance, certain dietary patterns that stimulate insulin secretion, including high intakes of red and processed meats, saturated and trans-fats, and highly processed carbohydrates and sugars, may increase the risk of colon cancer. There is evidence suggesting that some component of red meat may independently increase the risk of colorectal cancer, and some micronutrients may be important as protective agents. Currently, the evidence is strongest for folate and calcium. Folate may be especially important in alcohol drinkers because alcohol appears to increase the risk, particularly when folate intake is low. This interaction may be related to the antifolate properties of alcohol. In contrast to earlier studies, more recent epidemiologic studies have generally not supported a strong influence of dietary fiber or fruits and vegetables, although these have other health benefits, and their consumption should be encouraged. The majority of colon cancers, as well as many other conditions, may be prevented by lifestyle alterations in the intake of these nutritional factors, in addition to other factors, such as smoking.

This review provides an overview of the principal hypotheses and epidemiological evidence of the possible links between colorectal cancer and intake of milk and/or dairy products.

The first section outlines the main hypotheses about the possible effect of calcium, vitamin D, fats and other milk components. The possible role of acid lactic bacteria in fermented products is also discussed. The second section is a summary of the published epidemiological evidence. The results on milk, cheese and yoghurt are summarized using a meta-analytical approach. The results of studies on calcium and vitamin D are briefly described.

Case-control studies are heterogeneous and, on average, do not provide evidence of association between total intake of total dairy products, milk, cheese or yoghurt and colorectal cancer risk. The average result from cohort studies support the hypothesis of a protective effect of total dairy products (odds ratio (OR): 0.62; 95% confidence interval (CI): 0.52-0.74; P heterogeneity test: 0.93) and for milk (OR: 0.80; 95% CI: 0.68-0.95; P heterogeneity: 0.77). No association was found between cheese (OR: 1.10; 95% CI: 0.88-1.36; P heterogeneity: 0.55) or yoghurt (OR: 1.03; 95% CI: 0.83-1.28; P heterogeneity: 0.69) in cohort studies.

Cohort studies consistently found a protective effect of total dairy products and milk intake, but the evidence is not supported by case-control studies. No relationship was found with cheese or yoghurt intake. As the number of cohort studies is still limited, their results need to be confirmed by other prospective studies.

Based on current epidemiologic knowledge, public health recommendations to decrease total fat intake for the prevention of cancer appear largely unwarranted. Recommendations to decrease red meat intake, particularly processed meat or beef intake, may, on the other hand, decrease the risk of colorectal cancer and prostate cancer; it may have a beneficial effect on breast cancer as well, although the evidence is much less compelling in this regard. There appears to be no particular benefit regarding cancer prevention that would accrue from reducing fat intake from vegetable sources, and in the case of breast cancer, there is some suggestive but preliminary evidence that olive oil or other sources of monounsaturated fatty acids may modestly decrease risk. Overall, recommendations focused on controlling weight by regular physical activity and avoidance of excessive energy intake from all sources; increasing plant food intake; consuming a variety of whole grains, vegetables, and fruits; and decreasing red meat intake are likely to be more effective in decreasing risk of breast, colorectal, and prostate cancer than decreasing total fat intake. This conclusion is consistent with current recommendations for cancer prevention as promulgated by the American Cancer Society.

Although many mechanisms remain unclear, a large body of evidence indicates that several dietary and lifestyle factors are likely to have a major influence on the risk of colon cancer. Physical inactivity, excess body weight, and a central deposition of adiposity are consistent risk factors. Overconsumption of energy is likely to be one of the major contributors to the high rates of colon cancer in Western countries. Beyond their influence on energy balance, the independent role of specific macronutrients remain controversial. Red meat, processed meats, and perhaps refined carbohydrates contribute to risk. Recent evidence indicate that chronic hyperinsulinemia may increase risk of colon cancer. As insulin resistance and subsequent hyperinsulinemia is induced by excess energy intake and some aspects of the Western diet (e.g., saturated fats and refined carbohydrates), insulin may be a focus of factors influencing colon cancer risk. Recent evidence also points to a role of IGF-1, but our understanding of modifiable factors that influence levels of these is poor at present. Of note is that hyperinsulinemia increases free IGF-1 exposure [25]. High alcohol consumption, probably in combination with a diet low in some micronutrients such as folate and methionine, and smoking early in life are likely to increase risk of colon cancer. Recent epidemiologic studies have tended not to support a strong influence of fiber; instead, some micronutrients or phytochemicals in fiber-rich foods may be important. Folate is one such nutrient that has received attention lately and is being studied in randomized intervention trials. Agents with chemopreventive properties, such as aspirin and postmenopausal estrogens, have potential adverse effects so a careful consideration of the risk-benefit ratio is required before general recommendations can be made. Other NSAIDs with a potential for reduced toxicity, such as celecoxib, are currently being evaluated for efficacy and toxicity. The overwhelming evidence indicates that primary prevention of colon cancer is feasible. At least 70% of colon cancers may be preventable by moderate changes in diet and lifestyle [197]. Secondary prevention, through screening by sigmoidoscopy and colonoscopy, is also critically important to prevent mortality from colon cancer; however, many of the diet and lifestyle risk factors for colon cancers are the same for cardiovascular disease and for some other cancers, so focusing on the modifiable risk factors for colon cancer is likely to have many additional benefits beyond this cancer.

Steroid-hormone dependent cancers, including those of the breast, prostate and colon, are leading causes of morbidity and mortality in western countries. In rural Asian areas, these diseases are relatively uncommon. Dietary factors, including low consumption of fruit, vegetables and soy in the west have been shown in various epidemiologic studies as reasons for these differences. This review discusses flavonoids, one component of these plant foods that is being investigated for their role in chemoprevention. Epidemiological, in vitro, animal and human studies shall be explored to look at mechanisms involved, including steroid hormone activity, effects on cell growth, antioxidant activities, inhibition of chemical carcinogenesis and influences on modulators of cancer risk. Although the in vitro and animal models point to several pathways by which flavonoids may reduce incidence of these cancers, the clinical data are still relatively lacking. More research is needed to determine how best to use foods containing these compounds to reduce steroid hormone-dependent cancer risk.

The intent of this review is to critically analyze the scientific evidence on the role of the glycemic index in chronic Western disease and to discuss the utility of the glycemic index in the prevention and management of these disease states.

The glycemic index ranks foods based on their postprandial blood glucose response. Hyperinsulinemia and insulin resistance, as well as their determinants (eg high energy intake, obesity, lack of physical activity) have been implicated in the etiology of diabetes, coronary heart disease and cancer. Recently, among dietary factors, carbohydrates have attracted much attention as a significant culprit, however, different types of carbohydrate produce varying glycemic and insulinemic responses. Low glycemic index foods, characterized by slowly absorbed carbohydrates, have been shown in some studies to produce beneficial effects on glucose control, hyperinsulinemia, insulin resistance, blood lipids and satiety.

Studies on the short and long-term metabolic effects of diets with different glycemic indices will be presented and discussed. The review will focus primarily on clinical and epidemiological data, and will briefly discuss in vitro and animal studies related to possible mechanisms by which the glycemic index may influence chronic disease.

To investigate the relative risk factor of food items for colorectal cancer in four time periods through a case-control study in a Chinese rural area.

Colorectal cancer patients diagnosed at a county cancer center, Hebei Province, China, and non-cancer outpatients with similar age, sex, and place of residence were selected for cases and controls, respectively. There were 102 (93.6%) colorectal cancer patients and 99 (90.8%) outpatients being the cases and controls, respectively in the present investigation, who agreed to be interviewed about their food intake, during a 20-year period, through a food frequency questionnaire. The risks of intake of different food items and lifestyle for colorectal cancer were compared between cases and controls.

During the 20-year period, diets of both cases and controls changed with increase in intake of animal foods and fruits, and alcohol consumption tended to increase. In the food items, milk intake showed a protective effect in both males and females, and the odds ratios were 0.38 (95% CI 0.16-0.90) and 0.28 (95% CI 0.10-0.81) for males and females, respectively. A reduced risk of fruit intake could be seen in males, while a reduced risk of vegetables could be observed in females. Meat intake and saturated fats were the prominent risk factors for colorectal cancer in males and females, respectively. A comparison of life habits, showed that tea drinking had a consistent protective effect in females, and the odds ratios were 0.21 (0.08-0.58), 0.23 (0.08-0.67), 0.25 (0.10-0.64), and 0.11 (0.04-0.30) for periods of 20-, 10-, 5-years ago, and current time, respectively.

These findings indicate that change in food consumption is strongly associated with a change in risk of colorectal cancer, and dietary meat has increased the risk of colorectal cancer. Increase in the consumption of milk and fruits may be a significant measure for colorectal cancer prevention in low-incidence areas.

Colorectal cancer is the second most common malignancy in the Western world including the United Sates. In recent years there is a strong upward trend in colon cancer risk in Japan mainly due to Americanization of Japanese food habits. Several epidemiological studies point to a strong association between nutrient composition of the diet and cancer of the colon. The role of types of dietary fat, especially saturated fats of animal origin, n-6- and n-3-rich polyunsaturated fatty acids (PUFAs) in the etiology of colorectal cancer has become increasingly apparent. Epidemiological studies indicate a positive association between the dietary intake of saturated fat and/or animal fat and colon cancer risk and an inverse relationship between the intake of fish and fish oil rich in n-3 PUFAs and colon cancer development. Although the evidence from case-control studies and international correlational studies is not totally consistent, these inconsistencies may have arisen, at least in part, from methodological limitations. Animal, model studies have unequivocally provided evidence that the colon tumor-promoting effect of dietary fat depends on its fatty acid composition and that high dietary n-3 PUFAs lacks colon tumor-promoting effect, as compared to diets high in n-6 PUFAs or saturated fats. Diets rich in n-3 PUFAs inhibit colon carcinogenesis through the modulation of colonicras-p21, cyclooxygenase-2, and inducible nitric oxide synthase activities and apoptosis. Gene expression analysis using DNA microarrays indicates that n-3 fatty acid, docosahexaenoic acid activates cyclin-dependent kinase inhibitors such as p21, p27, p57 and p19 and inactivates antiapoptotic Bcl-2 family of genes, and prostagland in family of genes. These results suggest that decreasing the intake of n-6 PUFAs and saturated fats and increasing that of n-3 PUFAs, particularly eicosapentaenoic acid and docosahexaenoic acid has the potential to be a major component of colon cancer control.

Primary prevention of colonic adenomas and cancer through dietary interventions or chemoprevention has great appeal. This article discusses primary prevention goals and promising nutritional or chemopreventive strategies. There is substantial observational evidence that diets high in total calories and fat and or low in fruits and vegetables or total fiber as well as low levels of physical activity are related to the risk of colonic neoplasia. Similar observational data indicate that diets high in specific nutrients such as antioxidant vitamins or calcium may be protective. The article describes some of the newer chemopreventive agents and reviews the data linking diet and lifestyle to colorectal cancer risk, focusing on interventions that have also been studied in prospective clinical trials. Finally the evidence supporting the role of non-steroidal anti-inflammatory drugs for the chemoprevention of CRC is reviewed and the status of several other promising newer agents that are entering human trials is summarized.

The hypothesis that consumption of red and processed meat increases colorectal cancer risk is reassessed in a meta-analysis of articles published during 1973-99. The mean relative risk (RR) for the highest quantile of intake vs. the lowest was calculated and the RR per gram of intake was computed through log-linear models. Attributable fractions and preventable fractions for hypothetical reductions in red meat consumption in different geographical areas were derived using the RR log-linear estimates and prevalence of red meat consumption from FAO data and national dietary surveys. High intake of red meat, and particularly of processed meat, was associated with a moderate but significant increase in colorectal cancer risk. Average RRs and 95% confidence intervals (CI) for the highest quantile of consumption of red meat were 1.35 (CI: 1.21-1.51) and of processed meat, 1.31 (CI: 1.13-1.51). The RRs estimated by log-linear dose-response analysis were 1.24 (CI: 1.08-1.41) for an increase of 120 g/day of red meat and 1.36 (CI: 1.15-1.61) for 30 g/day of processed meat. Total meat consumption was not significantly associated with colorectal cancer risk. The risk fraction attributable to current levels of red meat intake was in the range of 10-25% in regions where red meat intake is high. If average red meat intake is reduced to 70 g/week in these regions, colorectal cancer risk would hypothetically decrease by 7-24%.

A variety of external factors interacting with genetic susceptibility influence the carcinogenesis process. External factors including oxidative compounds, electrophilic agents, and chronic infections may enhance genetic damage. In addition, various hormonal factors which influence growth and differentiation are critically important in the carcinogenic process. Diet and nutrition can influence these processes directly in the gastrointestinal tract by providing bioactive compounds to specific tissues via the circulatory system, or by modulating hormone levels. Differences in certain dietary patterns among populations explain a substantial proportion of cancers of the colon, prostate and breast. These malignancies are largely influenced by a combination of factors related to diet and nutrition. Their causes are multifactorial and complex, but a major influence is the widespread availability of energy-dense, highly processed and refined foods that are also deplete in fiber. These dietary patterns in combination with physical inactivity contribute to obesity and metabolic consequences such as increased levels of IGF-1, insulin, estrogen, and possibly testosterone. These hormones tend to promote cellular growth. For prostate cancer, epidemiologic studies consistently show a positive association with high consumption of milk, dairy products, and meats. These dietary factors tend to decrease 1.25(OH)2 vitamin D, a cell differentiator, and low levels of this hormone may enhance prostate carcinogenesis. While the nutritional modulation of growth-enhancing and differentiating hormones is likely to contribute to the high prevalence of breast, colorectal, prostate, and several other cancers in the Western world, these cancers are relatively rare in less economically developed countries, where malignancies of the upper gastrointestinal tract are quite common. The major causes of upper gastrointestinal tract cancers are likely related to various food practices or preservation methods other than refrigeration, which increase mucosal exposure to irritants or carcinogens.

The total free radical scavenger capacity (RSC) of 57 edible oils from different sources was studied: olive (24 brands of oils), sunflower (6), safflower (2), rapeseed (3), soybean (3), linseed (2), corn (3), hazelnut (2), walnut (2), sesame (2), almond (2), mixture of oils for salad (2), "dietetic" oil (2), and peanut (2). Olive oils were also studied according to their geographical origins (France, Greece, Italy, Morocco, Spain, and Turkey). RSC was determined spectrophotometrically by measuring the disappearance of the radical 2,2-diphenyl-1-picrylhydrazyl radical (DPPH(*)) at 515 nm. The disappearance of the radical followed a double-exponential equation in the presence of oils and oil fractions, which suggested the presence of two (fast and slow) groups of antioxidants. RSC was studied for the methanol-soluble phase ("methanolic fraction", MF) of the oil, the fraction nonsoluble in methanol ("lipidic fraction", LF), and the nonfractionated oil ("total oil"; TF = MF + LF). Only olive, linseed, rapeseed, safflower, sesame, and walnut oils showed significant RSC in the MF due to the presence of phenolic compounds. No significant differences were found in the RSC of olive oils from different geographical origins. Upon heating at 180 degrees C the apparent constant for the disappearance of RSC (k(T)) and the half-life (t1/2) of RSC for MF, LF, and TF were calculated. The second-order rate constants (k2) for the antiradical activity of some phenolic compounds present in oils are also reported.

Dietary agents that induce glutathione S-transferases and related detoxification systems (Phase 2 enzyme inducers) are thought to prevent cancer by enhancing elimination of chemical carcinogens. The present study shows that compounds of this group (benzyl isothiocyanate, allyl sulfide, dimethyl fumarate, butylated hydroxyanisole) activated apoptosis in human colon carcinoma (HT29) cells in culture over the same concentration ranges that elicited increases in enzyme activity (5-25, 25-100, 10-100, 15-60 micromol/L, respectively). Pretreatment of cells with sodium butyrate, an agent that induces HT29 cell differentiation, resulted in parallel increases in Phase 2 enzyme activities and induction of apoptosis in response to the inducers. Cell death characteristics included apoptotic morphological changes, appearance of cells at sub-G1 phase on flow cytometry, caspase activation, DNA fragmentation and TUNEL-positive staining. The results suggest that dietary Phase 2 inducers may protect against cancer by a mechanism distinct from and in addition to that associated with enhanced elimination of carcinogens. If this occurs in vivo, diets high in such compounds could eliminate precancerous cells by apoptosis at time points well after initial exposure to chemical mutagens and carcinogens.