Results from Egger’s tests indicated little evidence of publication bias in these studies (flavonols: P = 0.571, flavones: P = 0.106, flavan-3-ols: P = 0.890, flavanones: P = 0.964, anthocyanins: P = 0.449, and total flavonoids: P = 0.853).0.92 (0.82 1.03) 0.92 (0.85 0.99)0.081 0.60.3 90.0.88 (0.77 1.00) 0.86 (0.77 0.94)0.323 0.11.5 79.DiscussionStudies have suggested that plant Docosahexaenoyl ethanolamide flavonoids have many biological benefits, such as the antioxidant, anti-inflammatory, anti-tumor [37] and anti-atherosclerosis effects [38,39]. Cancer preventive phytochemicals, especially flavonoids, have been shown to suppress or block cancer progression by a variety of mechanisms [40,41]. More attention is given to preventing colon, rectum, lung, prostate or 548-04-9 Breast cancer through daily diet because of the chemoprotective effects of dietary flavonoids and other phytochemicals. However, most of the cancer preventive effects of0.96 (0.86 1.06) 0.90 (0.83 0.98)0.000 0.0.474 20.0.98 (0.86 1.11) 0.94 (0.84 1.05)0.281 0.21.3 0.doi:10.1371/journal.pone.0054318.tFlavonoids and Breast Cancer RiskFigure 3. Funnel plot of flavonoids consumption and risk of breast cancer. doi:10.1371/journal.pone.0054318.gphytochemicals, including flavonoids, were shown in animal and cell culture studies; human clinical trials examining the chemopreventive potential of phytochemicals are lacking. In fact, some 
epidemiologic studies assessing the association between the flavonoid intake and the breast cancer risk have yielded inconsistent results. Moreover, different dietary flavonoid subclasses, which vary in chemical structures and bioactivities, may have different chemopreventive effects on breast cancer. The present meta-analysis of population studies supports a significant association of flavonols and 10457188 flavones intake with a reduced risk of breast cancer. However, neither the total flavonoids nor the other flavonoid subclasses intake has been found to be associated withthe breast cancer risk. More studies are warranted to confirm the results. The findings likely provide useful insight and evidence that can be used by registered dietitians and other healthcare professionals when discussing diet and cancer prevention with patients. In establishing flavonoids as one of the contributors to the protective effects, the very first step is to estimate flavonoid intake from various dietary sources [21]. Yet dietary flavonoids are composed of a great variety of polyphenolic compounds which widely exist in plant foods, so it is difficult to assess the intake of total flavonoids and flavonoid subclasses. Part of the inconsistencies of epidemiological studies may be attributable to the difficultyFlavonoids and Breast Cancer Riskin measuring intake levels of flavonoids. The estimated daily intake of total flavonoids in the same country may differ in different studies, suggesting that some heterogeneity may exist in dietary assessment of flavonoids intake. Estimation of flavonoid intake from dietary sources has been feasible since 2003 when the U.S. Department of Agriculture (USDA) released the database for the flavonoid content of selected foods. Since then, many articles have been published in which flavonoid intake in various subpopulation groups was estimated from relatively large, current databases of flavonoid concentration data. Furthermore, biomarkers such as urinary excretion or plasma metabolite levels could complement dietary assessment of the bioavailability of these dietary compounds. Ho.Results from Egger’s tests indicated little evidence of publication bias in these studies (flavonols: P = 0.571, flavones: P = 0.106, flavan-3-ols: P = 0.890, flavanones: P = 0.964, anthocyanins: P = 0.449, and total flavonoids: P = 0.853).0.92 (0.82 1.03) 0.92 (0.85 0.99)0.081 0.60.3 90.0.88 (0.77 1.00) 0.86 (0.77 0.94)0.323 0.11.5 79.DiscussionStudies have suggested that plant flavonoids have many biological benefits, such as the antioxidant, anti-inflammatory, anti-tumor [37] and anti-atherosclerosis effects [38,39]. Cancer preventive phytochemicals, especially flavonoids, have been shown to suppress or block cancer progression by a variety of mechanisms [40,41]. More attention is given to preventing colon, rectum, lung, prostate or breast cancer through daily diet because of the chemoprotective effects of dietary flavonoids and other phytochemicals. However, most of the cancer preventive effects of0.96 (0.86 1.06) 0.90 (0.83 0.98)0.000 0.0.474 20.0.98 (0.86 1.11) 0.94 (0.84 1.05)0.281 0.21.3 0.doi:10.1371/journal.pone.0054318.tFlavonoids and Breast Cancer RiskFigure 3. Funnel plot of flavonoids consumption and risk of breast cancer. doi:10.1371/journal.pone.0054318.gphytochemicals, including flavonoids, were shown in animal and cell culture studies; human clinical trials examining the chemopreventive potential of phytochemicals are lacking. In fact, some epidemiologic studies assessing the association between the flavonoid intake and the breast cancer risk have yielded inconsistent results. Moreover, different dietary flavonoid subclasses, which vary in chemical structures and bioactivities, may have different chemopreventive effects on breast cancer. The present meta-analysis of population studies supports a significant association of flavonols and 10457188 flavones intake with a reduced risk of breast cancer. However, neither the total flavonoids nor the other flavonoid subclasses intake has been found to be associated withthe breast cancer risk. More studies are warranted to confirm the results. The findings likely provide useful insight and evidence that can be used by registered dietitians and other healthcare professionals when discussing diet and cancer prevention with patients. In establishing flavonoids as one of the contributors to the protective effects, the very first step is to estimate flavonoid intake from various dietary sources [21]. Yet dietary flavonoids are composed of a great variety of polyphenolic compounds which widely exist in plant foods, so it is difficult to assess the intake of total flavonoids and flavonoid subclasses. Part of the inconsistencies of epidemiological studies may be attributable to the difficultyFlavonoids and Breast Cancer Riskin measuring intake levels of flavonoids. The estimated daily intake of total flavonoids in the same country may differ in different studies, suggesting that some heterogeneity may exist in dietary 
assessment of flavonoids intake. Estimation of flavonoid intake from dietary sources has been feasible since 2003 when the U.S. Department of Agriculture (USDA) released the database for the flavonoid content of selected foods. Since then, many articles have been published in which flavonoid intake in various subpopulation groups was estimated from relatively large, current databases of flavonoid concentration data. Furthermore, biomarkers such as urinary excretion or plasma metabolite levels could complement dietary assessment of the bioavailability of these dietary compounds. Ho.
