Serum Carotenoids and Breast Cancer Rohan Invited Commentary: Serum Carotenoids and Breast Cancer

A vast amount of epidemiologic evidence suggests that a relatively high fruit and vegetable intake is associated with reduced risk of cancer (1). Although findings for breast cancer are less consistent than those for cancers at several other anatomic sites, including the mouth and pharynx, esophagus , stomach, and lung (1), a recent meta-analysis suggested that women with a relatively high vegetable consumption have a 25 percent reduction in breast cancer risk, and those with a relatively high fruit consumption have approximately a 6 percent reduction in risk (2). Vegetables and fruits contain numerous bioactive and potentially anticarcinogenic substances, including carotenes, dithiolthiones, flavonoids, indoles, isothiocyanates, phenols, folic acid, and vitamins C and E (3). The many possible mechanisms by which these substances might inhibit car-cinogenesis include antioxidant effects, increases in cell-to-cell communication, activation of enzymes involved in carcinogen detoxification, alteration of estrogen metabolism, effects on DNA methylation and repair, and antiproliferative effects (3). Much attention has been devoted to study of the association between carotenoids and cancer risk (1). Although more than 600 carotenoids have been identified in nature, diets in the United States typically include only about 40 carotenoids, and only about 20 carotenoids can be measured in human serum and tissues (4). Those carotenoids that have the highest blood concentrations in populations which have been studied in the United States are α-carotene, β-carotene, β-cryptoxanthin, lutein, lycopene, and zeaxanthin (4). The carotenoids are antioxidants and may therefore exert anti-carcinogenic effects by inhibiting the ability of free radicals to induce DNA damage (5). However, some carotenoids might operate by other means as well. For example, α-and β-carotene and β-cryptoxanthin can be metabolized to retinol and thereby induce epithelial cell differentiation (6), and α-and β-carotene can also inhibit cell proliferation (7). There have been many epidemiologic studies of the association between dietary carotenoids and breast cancer risk. Case-control studies have mostly shown inverse associations with carotenoid intake (and, in particular, with intake of β-carotene) (1, 8, 9), whereas the results of cohort studies have been divided fairly evenly between those showing no association and those showing some evidence of inverse associations (1, 10). Of those studies that have reported on breast cancer risk in association with dietary intake of both β-carotene and other carotenoids, one case-control study in premenopausal women showed inverse associations with intake of β-carotene and of lutein plus zeaxanthin but not with intake of α-carotene (11); one showed …