E7080, a novel inhibitor that targets multiple kinases, has potent antitumor activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibition

Flavonoids, which are found in certain plant foods, are thought to lower cancer risk through their antioxidant, antiestrogenic and antiproliferative properties. We examined the association of intake of total flavonoids and 7 flavonoid subclasses with risk of lung, colorectal, breast, pancreatic and upper aerodigestive cancer among women in a large prospective cohort study. Study participants were 34,708 postmenopausal women in the Iowa Women's Health Study who completed a food frequency questionnaire and were followed for cancer occurrence from 1986 through 2004. Flavonoid intake was estimated from 3 databases developed by the USDA Nutrient Data Laboratory (NDL). Hazard ratios (HR) for cancer risk were calculated across total flavonoid and flavonoid subclass intake categories. Interactions between smoking history and flavonoid intake were also examined. After multivariable adjustment, lung cancer incidence was inversely associated with intakes of flavanones (HR = 0.68; 95% CI: 0.53-0.86, all results highest vs. lowest quintile) and proanthocyanidins (HR = 0.75; 95% CI: 0.57-0.97). Among current and past smokers, those with intakes in the highest quintile for flavanones (HR = 0.66; 95% CI: 0.50-0.86), and proanthocyanidins (HR = 0.66; 95% CI; 0.49-0.89) had significantly lower lung cancer incidence than those in the lowest quintile. Similar associations were not seen in never smokers. Isoflavone intake was inversely associated with overall cancer incidence (HR = 0.93, 95% CI: 0.86-1.00). This study provides further support for a beneficial effect of flavonoid intake on lung cancer risk, especially among current and past smokers.     

Flavonoid and lignan intake and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort

Despite the potential cancer preventive effects of flavonoids and lignans, their ability to reduce pancreatic cancer risk has not been demonstrated in epidemiological studies. Our aim was to examine the association between dietary intakes of flavonoids and lignans and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 865 exocrine pancreatic cancer cases occurred after 11.3 years of follow‐up of 477,309 cohort members. Dietary flavonoid and lignan intake was estimated through validated dietary questionnaires and the US Department of Agriculture (USDA) and Phenol Explorer databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using age, sex and center‐stratified Cox proportional hazards models, adjusted for energy intake, body mass index (BMI), smoking, alcohol and diabetes status. Our results showed that neither overall dietary intake of flavonoids nor of lignans were associated with pancreatic cancer risk (multivariable‐adjusted HR for a doubling of intake = 1.03, 95% CI: 0.95–1.11 and 1.02; 95% CI: 0.89–1.17, respectively). Statistically significant associations were also not observed by flavonoid subclasses. An inverse association between intake of flavanones and pancreatic cancer risk was apparent, without reaching statistical significance, in microscopically confirmed cases (HR for a doubling of intake = 0.96, 95% CI: 0.91–1.00). In conclusion, we did not observe an association between intake of flavonoids, flavonoid subclasses or lignans and pancreatic cancer risk in the EPIC cohort.     

Dietary flavonoid intake and colorectal cancer risk in the European prospective investigation into cancer and nutrition (EPIC) cohort

Flavonoids have been shown to inhibit colon cancer cell proliferation in vitro and protect against colorectal carcinogenesis in animal models. However, epidemiological evidence on the potential role of flavonoid intake in colorectal cancer (CRC) development remains sparse and inconsistent. We evaluated the association between dietary intakes of total flavonoids and their subclasses and risk of development of CRC, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. A cohort of 477,312 adult men and women were recruited in 10 European countries. At baseline, dietary intakes of total flavonoids and individual subclasses were estimated using centre‐specific validated dietary questionnaires and composition data from the Phenol‐Explorer database. During an average of 11 years of follow‐up, 4,517 new cases of primary CRC were identified, of which 2,869 were colon (proximal = 1,298 and distal = 1,266) and 1,648 rectal tumours. No association was found between total flavonoid intake and the risk of overall CRC (HR for comparison of extreme quintiles 1.05, 95% CI 0.93–1.18; p‐trend = 0.58) or any CRC subtype. No association was also observed with any intake of individual flavonoid subclasses. Similar results were observed for flavonoid intake expressed as glycosides or aglycone equivalents. Intake of total flavonoids and flavonoid subclasses, as estimated from dietary questionnaires, did not show any association with risk of CRC development.     

Flavonoids and the risk of oral and pharyngeal cancer: a case-control study from Italy.

The intake of flavonoids has been inversely related to the risk of various common neoplasms, but scanty data exist on oral and pharyngeal cancer. We used data from a case-control study conducted in Italy between 1992 and 2005 to examine the relationship between flavonoid intake and oral and pharyngeal cancer risk. The study included 805 cases with incident, histologically confirmed oral and pharyngeal cancer, and 2,081 hospital controls admitted for acute, nonneoplastic conditions. We have applied data on food and beverage content of six major classes of flavonoids, on dietary information collected through a validated food-frequency questionnaire. The odds ratios (OR) were calculated using multiple logistic regression models, conditioned on study center, sex, and age. After adjustment for education, tobacco, alcohol, body mass index, and non-alcohol energy intake, ORs for the highest versus the lowest quintile of intake were 0.51 [95% confidence intervals (95% CI), 0.37-0.71] for flavanones, 0.62 (CI, 0.43-0.89) for flavonols, and 0.56 (95% CI, 0.40-0.78) for total flavonoids. No significant association emerged for isoflavones (OR, 0.90), anthocyanidins (OR, 0.86), flavan-3-ols (OR, 0.84), and flavones (OR, 0.75). The ORs were consistent across strata of age, sex, education, body mass index, tobacco, and alcohol. After allowance for vegetable and fruit consumption, the inverse relations with total flavonoids and flavanones remained significant, whereas that with flavonols became nonsignificant. None of the associations were significant after further allowance for vitamin C, probably on account of the high collinearity between these compounds.     

Flavonoids and breast cancer risk in Italy.

Few epidemiologic studies have investigated the potential relation between flavonoids and breast cancer risk. We have applied recently published data on the composition of foods and beverages in terms of six principal classes of flavonoids (i.e., flavanones, flavan-3-ols, flavonols, flavones, anthocyanidines, and isoflavones) on dietary information collected in a large-case control study of breast cancer conducted in Italy between 1991 and 1994. The study included 2,569 women with incident, histologically confirmed breast cancer, and 2,588 hospital controls. Odds ratios (OR) and 95% confidence intervals were estimated by multiple logistic regression models. After allowance for major confounding factors and energy intake, a reduced risk of breast cancer was found for increasing intake of flavones (OR, 0.81, for the highest versus the lowest quintile; P-trend, 0.02), and flavonols (OR, 0.80; P-trend, 0.06). No significant association was found for other flavonoids, including flavanones (OR, 0.95), flavan-3-ols (OR, 0.86), anthocyanidins (OR, 1.09), as well as for isoflavones (OR, 1.05). The findings of this large study of an inverse association between flavones and breast cancer risk confirm the results of a Greek study.     

Flavonoids and risk of squamous cell esophageal cancer

The relation between 5 classes of flavonoids (flavanones, flavan-3-ols, flavonols, flavones and anthocyanidines) and esophageal cancer was investigated using data from a case-control study conducted between 1992 and 1997 in 3 areas of northern Italy. The study included 304 cases (275 men, 29 women) with a first diagnosis of squamous-cell carcinoma of the esophagus and 743 controls (593 men, 150 women) with no history of cancer, admitted for acute illnesses, unrelated to tobacco and alcohol consumption, to major hospitals of the areas under surveillance. Dietary habits were investigated using a validated food frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals (CI) were computed after allowance for age, sex, study centre, years of education, alcohol drinking, tobacco smoking, body mass index and energy intake. An inverse association emerged between flavanone intake and esophageal cancer risk (OR=0.38 for the highest vs. the lowest quintile, 95% CI=0.23-0.66). The inverse relation between flavanones and esophageal cancer tended to be stronger in those who drank >or=6 drinks/day. In conclusion, this study suggests that flavanone intake is inversely associated with esophageal cancer risk and may account, with vitamin C, for the protective effect of fruit, especially citrus fruit, on esophageal cancer.     

Flavonoids and the risk of renal cell carcinoma.

Intake of flavonoids has been inversely related to the risk of various common neoplasms, but limited data exist on renal cell carcinoma (RCC). We used data from a case-control study conducted between 1994 and 2002 in four Italian areas to study the relation between major flavonoid classes and RCC. The study included 767 cases with incident, histologically confirmed RCC and 1,534 hospital controls admitted for acute, nonneoplastic conditions and matched with cases by study center, sex, and quinquennia of age. We applied published data on food and beverage content of six major classes of flavonoids to dietary information collected through a validated food frequency questionnaire. After adjustment for major recognized confounding factors and total energy intake, the odds ratios for subjects in the highest versus the lowest quintile of intake were 0.80 [95% confidence interval (95% CI), 0.58-1.11] for total flavonoids, 0.76 (95% CI, 0.56-1.03) for isoflavones, 0.94 (95% CI, 0.60-1.47) for anthocyanidins, 0.77 (95% CI, 0.56-1.06) for flavan-3-ols, 0.90 (95% CI, 0.67-1.21) for flavanones, 0.68 (95% CI, 0.50-0.93) for flavones, and 0.69 (95% CI, 0.50-0.95) for flavonols. Allowance for vegetable and fruit consumption only partly explained these inverse relations. Thus, flavonoids, and particularly flavones and flavonols, may account, at least in part, for the favorable role of plant foods on RCC.     

Flavonoid intake and risk of pancreatic cancer in male smokers (Finland).

Extending research on the protective effect of flavonoids in cell culture and animal studies, we examined the association between consumption of flavonoids and flavonoid-rich foods and development of exocrine pancreatic cancer within the alpha-Tocopherol, beta-Carotene Cancer Prevention Study cohort. Of the 27,111 healthy male smokers (50-69 years) who completed a self-administered dietary questionnaire at baseline, 306 developed exocrine pancreatic cancer during follow-up (1985-2004; median, 16.1 years). Intakes of total flavonoids, three flavonoid subgroups, seven individual flavonoids, and flavonoid-rich foods were estimated from a validated food frequency questionnaire. Hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards models. Overall, flavonoid intake was not significantly associated with pancreatic cancer. However, in stratified analysis, greater total flavonoid intake was associated with decreased pancreatic cancer risk in participants randomized during the trial to placebo (fourth versus first quartile: hazard ratio, 0.36; 95% confidence interval, 0.17-0.78; P trend = 0.009) and not to supplemental alpha-tocopherol (50 mg/d) and/or beta-carotene (20 mg/d; P interaction = 0.002). Similar patterns and significant interactions were observed for flavonols, flavan-3-ols, kaempferol, quercetin, catechin, and epicatechin. Our data suggest that a flavonoid-rich diet may decrease pancreatic cancer risk in male smokers not consuming supplemental alpha-tocopherol and/or beta-carotene.     

Flavonoids, vitamin C and adenocarcinoma of the stomach

OBJECTIVE: To examine the role of six flavonoid classes (flavanones, flavan-3-ols, flavonols, flavones, anthocyanidins and isoflavones) and vitamin C in the aetiology of stomach cancer. METHODS: Case-control study undertaken in Greece in the 1980s. Dietary information was obtained from 110 patients with incident stomach adenocarcinoma and 100 control patients. Flavonoid estimates were based on the recently released database of the US Department of Agriculture. RESULTS: In models including sociodemographic variables, energy intake, vegetables, fruits and, alternatively, vitamin C the six flavonoid classes, only flavanones and vegetables remained significantly inversely associated with stomach cancer risk. The odds ratio (95% confidence intervals) per one standard deviation increase of intake of flavanones was 0.55 (0.31-0.96) whereas for vitamin C it was 1.05 (0.46-2.41). When fruits and vegetables were not adjusted for, both vitamin C and several flavonoid categories were inversely associated with stomach cancer risk, but these associations could be attributed to other compounds in these foods. CONCLUSIONS: Among the major flavonoid classes studied, only flavanone intake is inversely associated with stomach cancer risk and could account for the apparent protective effect of fruit intake against this form of cancer. Additional factors, however, are likely to be involved in the consistent protection conveyed by vegetables.     

Flavonoid and lignan intake in relation to bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Background:

There is growing evidence of the protective role of dietary intake of flavonoids and lignans on cancer, but the association with bladder cancer has not been thoroughly investigated in epidemiological studies. We evaluated the association between dietary intakes of total and subclasses of flavonoids and lignans and risk of bladder cancer and its main morphological type, urothelial cell carcinoma (UCC), within the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Methods:

A cohort of 477 312 men and women mostly aged 35–70 years, were recruited in 10 European countries. At baseline, dietary flavonoid and lignan intakes were estimated using centre-specific validated questionnaires and a food composition database based on the Phenol-Explorer, the UK Food Standards Agency and the US Department of Agriculture databases.

Results:

During an average of 11 years of follow-up, 1575 new cases of primary bladder cancer were identified, of which 1425 were UCC (classified into aggressive (n=430) and non-aggressive (n=413) UCC). No association was found between total flavonoid intake and bladder cancer risk. Among flavonoid subclasses, significant inverse associations with bladder cancer risk were found for intakes of flavonol (hazard ratio comparing fifth with first quintile (HR_Q5–Q1) 0.74, 95% confidence interval (CI): 0.61–0.91; P-trend=0.009) and lignans (HR_Q5–Q1 0.78, 95% CI: 0.62–0.96; P-trend=0.046). Similar results were observed for overall UCC and aggressive UCC, but not for non-aggressive UCC.

Conclusions:

Our study suggests an inverse association between the dietary intakes of flavonols and lignans and risk of bladder cancer, particularly aggressive UCC.     

Flavonoids and ovarian cancer risk: A case-control study in Italy

Flavonoids belong to a vast group of polyphenols widely distributed in all foods of plant origin. Because of their antioxidant, antimutagenic and antiproliferative properties, they have been hypothesized to contribute to the favorable effects of fruit and vegetables against cancer. The aim of this study is to investigate the relation of 6 classes of flavonoids (flavan-3-ols, flavanones, flavonols, flavones, anthocyanidins and isoflavones) with ovarian cancer risk, using data from a multicentric case-control study conducted in Italy between 1992 and 1999. The study included 1,031 cases with incident, histologically confirmed epithelial ovarian cancer and 2,411 controls admitted for acute, nonneoplastic conditions to major hospitals in the same catchment areas. In logistic regression models including study center, education, year of interview, parity, oral contraceptive use and family history of ovarian or breast cancer or both, an inverse relation with significant trend in risk was found between ovarian cancer and flavonols [odds ratio (OR), 0.63; 95% confidence intervals (CI) 0.47-0.84] as well as isoflavones (OR, 0.51; 95% CI, 0.37-0.69), comparing the highest versus the lowest quintile. Further adjustment for fruit and vegetable intake did not modify these associations, suggesting that isoflavones and flavonols may have a distinct role in explaining the effect of fruit and vegetable against ovarian cancer. On the basis of our findings and the relevant literature, we infer that isoflavones, and perhaps flavonols, may have favorable effects with respect to ovarian cancer risk.     

Flavonoid intake and breast cancer risk: a case--control study in Greece

Flavonoids have been investigated for possible inverse associations with various chronic degenerative diseases, but there are no epidemiologic data concerning a possible association between several of the main flavonoid categories and breast cancer risk. We have applied recently published data on the flavonoid content of several foods and beverages on dietary information collected in the context of a large case-control study of 820 women with breast cancer and 1548 control women, conducted in Greece. We found a strong, statistically significant inverse association of flavone intake with breast cancer. The odds ratio for an increment equal to one standard deviation of daily flavone intake (i.e. 0.5 mg day(-1)) was 0.87, with 95% confidence interval 0.77-0.97. The association persisted after controlling for fruit and vegetable consumption, or for other flavonoid intake. This inverse association is compatible with and may explain the reported inverse association of breast cancer with consumption of vegetables, particularly leafy vegetables. After controlling for dietary confounding, there was no association of breast cancer risk with flavanones, flavan-3-ols, flavonols, anthocyanidins or isoflavones.     

Flavonoids and laryngeal cancer risk in Italy.

BACKGROUND: Flavonoids may play an important role in explaining the protective effect of vegetables and fruit against cancer. PATIENTS AND METHODS: To investigate the relation between flavonoids and laryngeal cancer risk, we have applied data on the composition of foods and beverages in terms of six principal classes of flavonoids to a case-control study of laryngeal cancer conducted from 1992 to 2000 in Italy. Cases were 460 subjects with incident, histologically confirmed laryngeal cancer; controls were 1088 patients admitted for acute, non-neoplastic diseases. Odds ratios (OR) were estimated through multiple logistic regression models, including terms for sociodemographic and lifestyle factors, tobacco smoking, alcohol consumption and energy intake. RESULTS: Significant inverse relations were found for the highest versus the lowest quintile of intake for flavan-3-ols (OR = 0.64), flavanones (OR = 0.60), flavonols (OR = 0.32) and total flavonoids (OR = 0.60), although the overall trends in risk were significant only for flavanones and flavonols. No consistent associations were observed for isoflavones, anthocyanidins and flavones. The estimates did not differ substantially across strata of alcohol drinking, tobacco smoking, body mass index and education, and tended to persist even after controlling for vegetable and fruit intake. CONCLUSION: This study provides support for a beneficial effect of selected flavonoids on laryngeal cancer risk.     

Flavonoid intake and ovarian cancer risk in a population‐based case‐control study

Several recent studies have evaluated the association between dietary flavonoid intake and ovarian cancer risk, and all reported significant or suggestive inverse associations with certain flavonoids or flavonoid subclasses; however, most of these studies were small to moderate in size. We, therefore, examined this association in a large, population‐based case‐control study. We calculated intake of 5 common dietary flavonoids (myricetin, kaempferol, quercetin, luteolin, and apigenin), as well as total intake of these flavonoids, for 1,141 cases and 1,183 frequency‐matched controls. We used unconditional logistic regression to estimate the relative risk (RR) of ovarian cancer for each quintile of flavonoid intake when compared with the lowest quintile. We did not observe an association between total flavonoid intake and ovarian cancer risk. The multivariable‐adjusted RR for the highest versus lowest quintile of total flavonoid intake was 1.06 (95% confidence interval [CI] = 0.78–1.45). In analyses of each individual flavonoid, only intake of apigenin was associated with a borderline significant decrease in risk (RR, highest vs. lowest quintile = 0.79, 95% CI = 0.59–1.06; p‐trend = 0.26), and this association was significant after adjustment for intake of the other 4 individual flavonoids (comparable RR = 0.72, 95% CI = 0.53–0.98; p‐trend = 0.09). These results provide limited support for an association between flavonoid intake and ovarian cancer risk. However, given the findings of previous studies and the biologic plausibility of this association, additional studies are warranted. © 2008 Wiley‐Liss, Inc.     

Dietary flavonoid intake and lung cancer--a population-based case-control study

BACKGROUND: Laboratory studies suggest that flavonoids are antimutagenic and anticarcinogenic. To investigate the associations between commonly consumed flavonoid compounds and lung cancer, the authors conducted a population-based case-control study of 558 lung cancer cases and a group of 837 controls. METHODS: Dietary intakes of flavonoids were estimated by combining the intake frequency (collected by a food frequency questionnaire), portion size, and food composition data. Unconditional logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence limits (95% CLs) with an adjustment for potential confounders, including age, sex, race-ethnicity, years of schooling, smoking status, pack-years of tobacco smoking, and daily energy intake. RESULTS: Lung cancer was associated inversely with the consumption of epicatechin (in 10 mg per day increment: OR, 0.64; 95% CL, 0.46-0.88), catechin (4 mg per day increment: OR, 0.49; 95% CL, 0.35-0.70), quercetin (9 mg per day increment: OR, 0.65; 95% CL, 0.44-0.95), and kaempferol (2 mg per day increment: OR, 0.68; 95% CL, 0.51-0.90) among tobacco smokers. There was little association between lung cancer and the flavonoid compounds mentioned above among nonsmokers. Regardless of smoking status, there was little association with total flavonoids: thearubigins, hesperetin, naringenin, and myricetin. In addition, consumption of vegetables, tea, and wine, all of which are rich sources of flavonoids, was associated inversely with lung cancer among tobacco smokers. CONCLUSIONS: Certain flavonoid compounds, including epicatechin, catechin, quercetin, and kaempferol, were associated inversely with lung cancer among tobacco smokers, but not among nonsmokers. Further studies of these associations may be warranted.     

Flavonoids and colorectal cancer in Italy.

Because of their several biological activities, flavonoids may have an important role in explaining the protective effects of vegetables, fruit, and, possibly, tea against cancer. The potential relation between flavonoids and colorectal cancer risk was investigated using data from a multicentric Italian case-control study, including 1,953 cases of colorectal cancers (1,225 colon cancers and 728 rectal cancers) and 4,154 hospital controls admitted for acute nonneoplastic diseases. We have applied recently published data on the composition of foods and beverages, in terms of six principal classes of flavonoids, on dietary information collected through a validated food-frequency questionnaire. Odds ratios (OR) were estimated by multiple logistic regression models, including terms for sex, age, study center, family history of colorectal cancer, education, alcohol consumption, body mass index, physical activity, and energy intake. A reduced risk of colorectal cancer was found for increasing intake of isoflavones (OR, 0.76, for the highest versus the lowest quintile, P(trend) = 0.001), anthocyanidins (OR, 0.67, P(trend) < 0.001), flavones (OR, 0.78, P(trend) = 0.004), and flavonols (OR, 0.64, P(trend) < 0.001). No significant association was found for flavan-3-ols (OR, 0.98), flavanones (OR, 0.96), and total flavonoids (OR, 0.97). The estimates did not substantially differ for colon and rectal cancers, as well as in strata of sex, age, and body mass index. The findings of this large study provide support for an inverse association of selected classes of flavonoids with colorectal cancer risk.     

Dietary flavonoids and the risk of colorectal cancer.

In vitro and in vivo laboratory data point to chemoprotective effects of flavonoids on colorectal cancer. However, there has been limited epidemiologic research on the dietary intake of flavonoids and risk of colorectal cancer. Recent expansions of dietary databases to include flavonoid data now make such studies feasible. Association between the six main classes of flavonoids and the risk of colorectal cancer was examined using data from a national prospective case-control study in Scotland, including 1,456 incident cases and 1,456 population-based controls matched on age, sex, and residence area. Dietary, including flavonoid data, were obtained from a validated, self-administered food frequency questionnaire. Risk of colorectal cancer was estimated using conditional logistic regression models in the whole sample and stratified by sex, smoking status, and cancer site and adjusted for established and putative risk factors. After energy adjustment, reductions in colorectal cancer risk associated with the highest quartiles of intake (versus the lowest quartile) were 27% for flavonols [odds ratio (OR), 0.73; P(trend) = 0.012], 32% for quercetin (OR, 0.68; P(trend) = 0.001), 32% for catechin (OR, 0.68; P(trend) < 0.0005); 26% for epicatechin (OR, 0.74; P(trend) = 0.019), and 22% for procyanidins (OR, 0.78; P(trend) = 0.031). The significant dose-dependent reductions in colorectal cancer risk that were associated with increased consumption of flavonols, quercetin, catechin, and epicatechin remained robust after controlling for overall fruit and vegetable consumption or for other flavonoid intake. The risk reductions were greater among nonsmokers, but no interaction beyond a multiplicative effect was present. Sex-specific or cancer-type differences were not observed. No risk reductions were associated with intake of flavones (P(trend) = 0.64), flavonones (P(trend) = 0.22), and phytoestrogens (P(trend) = 0.26). This was the first of several a priori hypotheses to be tested in this large study and showed strong and linear inverse associations of flavonoids with colorectal cancer risk.     

Association between habitual dietary flavonoid and lignan intake and colorectal cancer in a Spanish case–control study (the Bellvitge Colorectal Cancer Study)

Background

Flavonoid-rich foods, such as fruits, vegetables, and tea, may have a protective effect upon colorectal cancer. However, current epidemiological evidence for a protective effect of flavonoid intake upon colorectal cancer is promising but not conclusive.

Objective

To examine the relation between dietary flavonoid and lignan intakes and the risk of colorectal cancer within a Spanish population.

Design

Data from the Bellvitge Colorectal Cancer Study, a case–control study (424 cases with incident colorectal cancer and 401 hospital-based controls), were used. A reproducible and validated food frequency questionnaire was administered in personal interviews. An ad hoc food composition database on flavonoids and lignans was compiled, mainly using data from the US Department of Agriculture and Phenol-Explorer databases. Adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated using unconditional logistic regression models.

Results

An inverse association was found between intake of total flavonoids (OR, 0.59; 95 % CI, 0.35–0.99 for the highest vs. the lowest quartile; p for trend = 0.04), lignans (OR, 0.59; 95 % CI, 0.34–0.99; p for trend = 0.03), and some individual flavonoid subgroups (flavones, proanthocyanidins) and the risk of colorectal cancer. Separate analyses by cancer site showed similar results.

Conclusions

Intake of total dietary flavonoids (particularly certain flavonoid subgroups) and lignans was inversely associated with colorectal cancer risk in a Spanish population.     

Diet and prostate cancer risk in a cohort of smokers, with a specific focus on calcium and phosphorus (Finland)

Background:Calcium, phosphorus, fructose, and animal protein are hypothesized to be associated with prostate cancer risk, potentially via their influence on 1,25-dihydroxyvitamin D₃. We examined these nutrients and overall diet and prostate cancer risk in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study (ATBC Study). Materials and methods:The ATBC Study was a randomized 2 × 2 trial of alpha-tocopherol and beta-carotene on lung cancer incidence conducted among Finnish male smokers; 27,062 of the men completed a food-use questionnaire at baseline, and comprise the current study population. There were 184 incident clinical (stage 2–4) prostate cancer cases diagnosed between 1985 and 1993. We used Cox proportional hazards models to examine associations between dietary intakes and prostate cancer. Results:We did not observe significant independent associations for calcium and phosphorus and prostate cancer risk. However, men with lower calcium and higher phosphorus intake had a multivariate relative risk of 0.6 (95% CI 0.3–1.0) compared to men with lower intakes of both nutrients, adjusting for age, smoking, body mass index, total energy, education, and supplementation group. Of the other foods and nutrients examined, none was significantly associated with risk. Discussion:This study provides, at best, only weak evidence for the hypothesis that calcium and phosphorus are independently associated with prostate cancer risk, but suggests that there may be an interaction between these nutrients.     

Flavonoid intake and liver cancer: a case–control study in Greece

In the context of a case–control study undertaken in Greece, we examined the role of six flavonoid classes in the etiology of hepatocellular carcinoma (HCC), by viral status, and of cholangiocarcinoma (CAC). Data and blood samples were collected between 1995 and 1998. Information about dietary intakes and covariates, including chronic infection with hepatitis B (HBV) and C (HCV) virus, were available for 250 HBV and/or HCV positive HCC cases, 83 HBV and HCV negative HCC cases, six CAC cases, and 360 hospital controls. In logistic regression models including gender, age, education, tobacco smoking, and total energy intake, there were no distinct patterns with respect to either HCC virus positive and HCC virus negative in relation to total flavonoids or any class of flavonoids, with the exception of flavones. Flavone intake, mostly derived from spinach and peppers, was inversely associated with both virus positive (P-trend, 0.049) and virus negative (P-trend, 0.084) HCC. There was also a suggestion of an inverse association of CAC with flavan-3-ols, anthocyanidins, and total flavonoids which, however, has to be taken with due caution on account of the small number of cases of this rare tumor. We conclude that flavones may be inversely associated with HCC risk, irrespective of its dominant etiology (viral or non viral).