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on tumor biomarkers is still very limited. The comparison of a 6-wk consumption of an isoflavone-rich and isoflavone-poor soy beverages providing 69 and 3 mg/d isoflavones, respectively, failed to show any impact of isoflavones on two tumor biomark- ers in 34 elderly men with elevated PSA.159 On the other hand, the consumption of a soy-containing diet providing an average of 154 mg/d isoflavones by 10 women during 1 mo resulted in a significative decrease of estradiol and progesterone plasmatic levels, two biomarkers for breast cancer risk.160 More stud- ies are needed to establish dietary recommendations for cancer patients. Polyphenol supplements might be useful as adjuvants in chemotherapy or radiotherapy treatments. Some polyphenols were shown to reinforce the antiproliferative activities of anticancer drugs. EGCG showed synergistic effects with sulin- dac or tamoxifen on apoptosis of the lung cancer cell line PC-9,161 and quercetin potentiated the growth inhibition of ovar- ian cancer cells and leukemia cells by cisplatin.162,163 The oral administration of green tea to Ehrlich ascites carcinoma tumor- bearing mice enhanced the anti-tumor activity of doxorubicin.164 However, such adjuvant effects vary widely between polyphe- nols. Galangin, when tested on leukemia cells, showed opposite effects to quercetin and inhibited the anti-apoptotic effects of cisplatin.163 Tangeretin, a citrus polymethoxylated flavonoid, when added to the diet of nude mice, inhibited the cytotoxic effects of tamoxifen on MCF-7 breast cancer cell inoculated subcutaneously.165 Clinical trials will be needed to establish adjuvant effects of the most promising polyphenols in cancer patients. The associations between the consumption of coffee, tea, and wine and the risk of cancer have been studied in different epi- demiological studies. The consumption of coffee has been asso- ciated to a reduced risk of colorectal cancer but not with cancers at other sites.166 Experimental evidence on tea strongly suggests a protective role of tea consumption against cancers, but the epi- demiological evidence is inconclusive. Although some inverse associations between stomach or colon cancer risk and tea con- sumption were observed in some case-control and prospective cohort studies,167,168 the majority of ecologic, cohort, or case- control studies suggest that tea drinking has no clear effect on cancer, possibly due to the much lower intake compared to the animal experiments.169−172 The possible existence of confound- ing factors in epidemiological studies has also been proposed to explain such discrepencies. A prospective study has suggested that wine polyphenols may protect against the deleterious effects of alcohol on can- cers of the upper digestive tract. The consumption of alcoholic beverages, such as beer or spirits, increased the risk of upper digestive tract cancer in a Danish cohort, whereas a moderate consumption of wine did not increase this risk.173 Another study on the same cohort also suggested the protective effects of wine consumption against lung cancer.174 However, the existence of some confounding factors cannot be excluded, as a positive cor- relation between esophagal cancer risk and wine consumption was observed in a case-control study carried out in Italy, where wine is the most common alcoholic beverage.175 An increase of esophageal cancer risk was observed in people consuming 3 glasses of wine or more per d, as compared to those consuming less than 3 glasses. If wine may appear less toxic with regard to cancer risk than other alcoholic beverages, it should be, in the present state of our knowledge, regarded as a risk factor rather than a protective factor, as it was found to increase the risk of gastric, breast, and lung cancer in several epidemiolog- ical studies.176−179 Furthermore, encouraging a moderate wine consumption may also result in an increase of alcoholism.180 Different attempts have been made to directly relate the in- take of some polyphenols to the risk of cancer. Flavonol intake (quercetin and kaempferol) was inversely associated to the risk of lung cancer in 5 case-control and cohort studies,181−185 but no association was found in 3 other studies.109,186,187 For cancers at sites other than the lung, no association was found with flavonol intake in 3 large prospective studies,109,182,185 but 2 case-control studies showed a lower risk of cancer of the stomach and of the upper-aerodigestive tract at high flavonol intake.188,189 Catechin intake was not significantly associated to cancer in a cohort of Dutch men,190 but an inverse association was found with rectal cancer in a large American cohort of postmenopausal women.191 The intake of catechin originating from fruits, but not from tea, was also associated to a lower risk of cancer of the upper-digestive tract in the same American cohort,191 whereas the urinary excretion of epigallocatechin was inversely associ- ated to gastric and esophageal cancer in a nested case-control study carried out in Shangai.167 The consumption of dietary sources of phytoestrogens has been repeatedly associated to a lower cancer risk. Epidemiolog- ical studies have suggested a protective role of the consumption of soy products, rich in isoflavones, against various cancers and, more particularly, hormone-related cancers.192 The consump- tion of whole-grain cereals, a major source of lignans, has also been associated to a reduced risk of various cancers.193 Several attempts were made to relate the exposure to dietary phytoestro- gens to cancer risk. Three case-control studies showed a lower urinary excretion of isoflavones or lignans in breast cancer pa- tients compared to controls,194−196 but no significative associa- tion with genistein and enterolactone excretion was found in an- other study.197 Other authors found more a complex relationship with a higher risk of breast cancer associated to both the lowest and the highest plasma levels of enterolactone.198 Similar stud- ies on prostate cancer suggested either a protective effect199,200 or no association201 with isoflavone or lignan exposure. Altogether, the epidemiological data on polyphenols and can- cer do not appear conclusive. It is possible that protective effects are limited to sub-groups of the population with particular geno- types or at a higher risk of developing disease.202 The causative role of dietary polyphenols, when a protective role is suggested, in observational studies must also be questionned. An associa- tion of myricetin or kaempferol intake with a lower prostate or gastric cancer risk has been reported,181,188 but such an associ- ation could be explained by some unknown confunding factors, as average daily intakes of myricetin and kaempferol do not DIETARY POLYPHENOLS AND DISEASE PREVENTION 293PDF Image | Dietary Polyphenols and the Prevention of Diseases
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