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

Flavonoids are naturally occurring substances in plants (Peterson and Dwyer, 1998). For five categories of flavonoids, namely flavones, flavonols, flavan-3-ols, flavanones and anthocyanidins, food composition data have been recently published by the US Department of Agriculture (US Department of Agriculture, 2003), while for a sixth category, that of isoflavones, food composition data have been available for some time (US Department of Agriculture-Iowa State University, 2002). Flavones, such as apigenin and luteolin, are present chiefly in grains, leafy vegetables and herbs. Flavonols are present in many plant foods: they include the glycosides of quercetin in fruits, leaves and vegetables; kaempferol in many fruits and leafy vegetables; isorhamnetin in onions and pears; and myricetin in berries, maize and tea. Flavan-3-ols, specifically the catechines, are abundant in ripe fruits, leaves, tea and chocolate. The major sources of the flavanone class in foods are citrus fruits and juices. The anthocyanidins are most abundant in fruits and less frequent in cereals and vegetables. The isoflavones include the compounds daidzein and genistein and are found mainly in soya and soya products (Peterson and Dwyer, 1998). As several flavonoids have antioxidant properties, as well as antimutagenic and antiproliferative properties in vitro (Kandaswami et al, 1992; Franke et al, 1998; Takahashi et al, 1998; Le Marchand et al, 2000), these compounds have been investigated for possible inverse associations with various chronic diseases, including cardiovascular diseases and several forms of cancer. Studies have suggested that flavonoid intake may be associated with reduced risks of certain types of cancer (Stoner and Mukhtar, 1995; Barnes et al, 1996) and coronary heart disease (Hertog et al, 1995; Hollman et al, 1996). A special interest on breast cancer stems from the fact that several flavonoids, particularly isoflavones, have also antioestrogenic effects (So et al, 1997; Papas, 1999). Some (Ingram et al 1997; Zheng et al, 1999; Murkies et al, 2000; Dai et al, 2002) but not all (den Tonkelaar et al, 2001) studies have found that diets high in isoflavones are associated with decreased breast cancer risk. All these studies have relied on urinary excretion measurements, which can theoretically be affected by disease status. We have found no published epidemiologic data concerning a possible association between intake of any of the indicated other categories of flavonoids and breast cancer risk. The objective of the present investigation was to ascertain whether one or more of the studied flavonoid categories was associated with breast cancer risk. For this purpose, we applied recently published data on the flavonoid content of several foods and beverages (US Department of Agriculture-Iowa State University, 2002; US Department of Agriculture, 2003) on dietary information collected in the context of a large case–control study of breast cancer, conducted in Greece in the early 1990 s. In that study (Katsouyanni et al, 1994; Trichopoulou et al, 1995), no association was found between intake of energy-generating nutrients and breast cancer risk, but consumption of fruits and vegetables was inversely associated with the risk.