Flavonoid intake and colorectal cancer risk in men and women. Dietary flavonoids and colorectal adenoma recurrence in the Polyp Prevention Trial. Dietary flavonoids and the risk of colorectal cancer. Dietary intake of selected flavonols, flavones, and flavonoid-rich foods and risk of cancer in middle-aged and older women. Dietary flavonoid intake and risk of cancer in postmenopausal women: the Iowa Women's Health Study. Dietary isoflavone and the risk of colorectal adenoma: a case-control study in Japan. High vegetable and fruit diet intervention in premenopausal women with cervical intraepithelial neoplasia. Exploring the feasibility and effects of a high-fruit and -vegetable diet in healthy women. Prospective study of diet and female colorectal cancer: the New York University Women's Health Study.
Dietary flavonoids can inhibit cancer development by protecting tissues against free oxygen radicals and inhibiting cell proliferation, but observational studies of flavonoid intake and colorectal cancer incidence are sparse. The authors prospectively evaluated the association between intake of flavonoids and colorectal cancer incidence in 71,976 women from the Nurses' Health Study and 35,425 men from the Health Professionals Follow-Up Study. Dietary intake was assessed in 1990, 1994, and 1998 by means of a food frequency questionnaire. The authors used Cox proportional hazards models with time-varying variables to estimate relative risks of colorectal cancer. Between 1990 and 2000, the authors documented 878 incident cases of colorectal cancer (498 in women and 380 in men). Total flavonoid intake was not inversely associated with colorectal cancer risk among women and men combined. The combined relative risk for the highest quintile of total flavonoid intake compared with the lowest was 1.19 (95% confidence interval: 0.94, 1.49; p for trend = 0.15). Higher intakes of individual flavonols, including quercetin, myricetin, and kaempferol, were also not related to a lower risk of colorectal cancer. These data provide little support for the hypothesis of an association between flavonoid intake and colorectal cancer risk, at least within the ranges of intakes consumed in the populations studied. Two recent case-control studies suggested that some flavonoid subgroups may play a role in preventing colorectal cancer. Previous prospective cohort studies generally reported no association; however, only a small subset of flavonoids was evaluated and partial flavonoid databases were used. We used the newly constructed U.S. Department of Agriculture flavonoid database to examine the association between consumption of total flavonoids, 6 flavonoid subgroups, and 29 individual flavonoids with adenomatous polyp recurrence in the Polyp Prevention Trial. The Polyp Prevention Trial was a randomized dietary intervention trial, which examined the effectiveness of a low-fat, high-fiber, high-fruit, and high-vegetable diet on adenoma recurrence. Intakes of flavonoids were estimated from a food frequency questionnaire. Multivariate logistic regression models (adjusted for age, body mass index, sex, regular non-steroidal anti-inflammatory use, and dietary fiber intake) were used to estimate odds ratios and 95% confidence intervals for both any and advanced adenoma recurrence within quartiles of energy-adjusted flavonoid intake (baseline, during the trial, and change during the trial). Total flavonoid intake was not associated with any or advanced adenoma recurrence. However, high intake of flavonols, which are at greater concentrations in beans, onions, apples, and tea, was associated with decreased risk of advanced adenoma recurrence (4th versus 1st quartile during the trial; odds ratio, 0.24; 95% confidence interval, 0.11, 0.53; P(trend) = 0.0006). Similar inverse associations were observed to a smaller extent for isoflavonoids, the flavonol kaempferol, and the isoflavonoids genistein and formononetin. Our data suggest that a flavonol-rich diet may decrease the risk of advanced adenoma recurrence. 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. Flavonoids may protect against cancer development through several biological mechanisms. However, epidemiologic studies on dietary flavonoids and cancer risk have yielded inconsistent results.
                We prospectively investigated the association between the intake of selected flavonoids and flavonoid-rich foods and risk of cancers in the Women's Health Study.
                A total of 3234 incident cancer cases were identified during 11.5 y of follow-up among 38,408 women aged > or = 45 y. Intake of individual flavonols (quercetin, kaempferol, and myricetin) and flavones (apigenin and luteolin) was assessed from food-frequency questionnaires. Cox regression models were used to estimate the relative risk (RR) of total and site-specific cancer across increasing intakes of total and individual selected flavonoids and flavonoid-rich foods (tea, apple, broccoli, onion, and tofu).
                The multivariate RRs of total cancer across increasing quintiles of total quantified flavonoid intake were 1.00, 1.00, 0.93, 0.94, and 0.97 (P for trend = 0.72). For site-specific cancers, the multivariate RRs in the highest quintile of total quantified flavonoid intake compared with the lowest quintile were 1.03 for breast cancer, 1.01 for colorectal cancer, 1.03 for lung cancer, 1.15 for endometrial cancer, and 1.09 for ovarian cancer (all P > 0.05). The associations for the individual flavonoid intakes were similar to those for the total intake. There was also no significant association between intake of flavonoid-rich foods and the incidence of total and site-specific cancers.
                Our results do not support a major role of 5 common flavonols and flavones or selected flavonoid-rich foods in cancer prevention. 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. We conducted a case-control study in a Japanese population to investigate the association between dietary isoflavone intake and the risk of colorectal adenoma. Participants who underwent magnifying colonoscopy with dye spreading as part of a cancer screening programme responded to a self-administered questionnaire, which included lifestyle information and intake of 145 food items, before the colonoscopy. A total of 721 case and 697 control subjects were enrolled. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models. We found a significant inverse association between dietary isoflavone intake and the risk of colorectal adenoma in men and women combined. However, the inverse association was not linear; rather, all quartiles above the first showed a similar decrease in risk, with multivariable-adjusted ORs and 95% CIs compared with the lowest quartile of 0.77 (0.57-1.04), 0.76 (0.56-1.02) and 0.70 (0.51-0.96) in the second, third and highest quartiles, respectively (P for trend=0.03). Of interest, the observed association was more prominent in women than in men. The observed ceiling effect associated with higher isoflavone intake suggests that a lower intake of dietary isoflavone might be associated with an increased risk of colorectal adenoma in Japanese populations. To examine whether diet intervention can promote increased vegetable and fruit intake, as reflected in increased plasma carotenoid and decreased plasma total homocysteine concentrations, in premenopausal women with cervical intraepithelial neoplasia, a precancerous condition.
                Randomized controlled diet intervention study.
                Fifty-three free-living premenopausal women who had been diagnosed with cervical intraepithelial neoplasia, were randomly assigned to an intervention (n = 27) or a control (n = 26) group.
                Individualized dietary counseling to increase vegetable and fruit intake.
                Diet was assessed by food frequency questionnaire. Plasma carotenoids and total homocysteine were measured at enrollment and at 6 months follow up.
                Associations between baseline plasma concentrations of carotenoids and homocysteine and influencing factors were examined with multiple regression analysis. Repeated measures analysis of variance was used to test for group by time effects in these plasma concentrations. Plasma carotenoids at baseline and 6 months in the study groups, and differences in homocysteine concentrations from baseline to 6 months, were compared with independent sample t tests.
                Repeated measures analysis of variance showed significant group by time effects (P<.01) in plasma carotenoid and homocysteine concentrations. In the intervention group, total plasma carotenoids increased by an average of 91%, from 2.04+/-0.13 (mean+/-standard error of the mean) to 3.90+/-0.56 micromol/L and plasma total homocysteine was reduced by 11%, from 9.01+/-0.40 to 8.10+/-0.44 micromol/L (P<.003). Neither changed significantly in the control group.
                Individualized dietary counseling can effectively promote increased vegetable and fruit intake in premenopausal women. This dietary pattern may reduce risk for cancer and other chronic diseases and also promote an improvement in folate status. Based on reports that fruits and vegetables may protect against breast cancer, this randomized intervention study tested the feasibility of increasing fruit and vegetable intake among healthy women to 9 daily servings through individual dietary counseling and group activities. Adherence to the dietary recommendations was monitored by 24-h food recalls, log sheets, and plasma carotenoid assessments. To explore possible cancer protective mechanisms of fruits and vegetables, we investigated the treatment effect on plasma phenol levels and on thiobarbituric acid-reactive substances measured as malondialdehyde equivalents, a possible marker of oxidative damage. At baseline, women in the intervention (n = 13) and control (n = 16) group reported an average daily consumption of 3.3 and 3.2 fruit and vegetable servings, respectively. After 3 and 6 months of intervention, intake in the intervention group had increased to 8.3 and 7.4 servings, whereas the control group reported an average of 4.2 and 4.1 daily servings. An increase of plasma carotenoid levels from 1249 microg/liter at baseline to 1854 and 1827 microg/liter after 3 and 6 months confirmed compliance with the dietary recommendations in the intervention group. Plasma carotenoid levels among controls changed slightly from 1165 to 1231 and 1291 microg/liter Whereas total phenol levels did not respond according to our hypothesis, malondialdehyde levels decreased slightly in the intervention group. These results suggest that motivated women can substantially increase their fruit and vegetable intake, which leads to a notable increase in plasma carotenoid levels. The relation between diet and female colorectal cancer was analyzed in a prospective study of 14,727 women aged 34-65 years, who were enrolled at mammographic screening clinics in New York and Florida from 1985 to 1991. They were followed through the end of 1994 (average 7.1 yrs) by a combination of direct contact through mail and telephone and record linkages with regional tumor registries, resulting in 100 incident cases of colorectal cancer. There was no overall positive or inverse association of colorectal cancer risk with intakes of total calories, total or subclasses of fat, carbohydrate, or dietary fiber, whereas there was an inverse association with total protein. Among major food groups, there was a progressive decline in risk of colorectal cancer with increasing intake of fish and shellfish (relative risk for 4th vs. 1st quartile = 0.49, 95% confidence interval = 0.27-0.89). A similar inverse association was also observed for consumption of dairy products, and this association was explained mainly by calcium, not by other nutrients, such as fat or protein. The results of the present study indicated that certain dietary components of fish or dairy products may protect against colorectal cancer, whereas the relations with red meat or total fat remained unclear.
There is insufficient and conflicting evidence regarding flavonoid intake and the prevention of colorectal neoplasms. It is difficult to determine flavonoid intake. Therefore, more evidence is needed to clarify the association between flavonoids and colorectal neoplasms.