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High dietary intake of lutein has been associated with reduced risk of some cancers, most notably endometrial and ovarian cancer, but not all cancers, according to epidemiological evidence (Freudenheim et al 1996, Fung et al 2003, Gann et al 1999, Giovannucci et al 1995, Huang et al 2003, Ito et al 2003, Lu et al 2001, McCann et al 2000, Michaud et al 2000, Nomura et al 1997, Schuurman et al 2002, Terry et al 2002).

Lung cancer The link between carotenoid intake and lung cancer has undergone extensive scrutiny and extensive epidemiological evidence suggests a reduction in lung cancer risk with high dietary intake of carotenoids (Cooper et al 1999). Initial research used food composition tables and therefore focused on beta-carotene, for which data was available; however, the dietary intake of beta-carotene and other carotenoids such as lutein and zeaxanthin are highly correlated (Ascherio et al 1992) and as food composition data for these nutrients has become available studies have suggested a link between dietary lutein intake and reduced lung cancer risk (Cooper et al 1999).

Three large population studies of diet and lung cancer have revealed a nonsignificant association between high lutein intake and lower risk of lung cancer (Ito et al 2003, Michaud et al 2000, Ziegler et al 1996), and a significant trend was observed in another population-based case-control study (Le Marchand et al 1993). A nested case control study also found that serum lutein and zeaxanthin were lower in those with lung cancer than in controls (Comstock et al 1997). These results are contrasted with those from a case-control study of 108 cases of lung cancer in a Chinese occupational cohort that found that higher serum carotenoid levels, including lutein and zeaxanthin, were significantly associated with increased lung cancer risk among alcohol drinkers, while having a possible protective association among non-drinkers (Ratnasinghe et al 2000).

Cervical cancer A recent systematic review suggests that lutein/zeaxanthin is likely to have a protective effect for cervical neoplasia and possibly for human papilloma virus persistence (Garcia-Closas et al 2005).

Endometrial cancer An epidemiological study involving 232 patients with endometrial cancer and 639 controls found that an intake of more than 7.3 mg/day of lutein was associated with a 70% reduced risk of endometrial cancer (McCann et al 2000).

Ovarian cancer A case-control study found that weekly intake of lutein of more than 24 mg was associated with a 40% reduction in the risk for developing ovarian Lutein and Zeaxanthin 815

cancer compared with weekly consumption of less than 3.8 fjg (Bertone et al 2001).

Breast cancer High lutein and zeaxanthin intake has been related to reduced risk of breast cancer (Dorgan et al 1998, Toniolo et al 2001). High lutein intake (>7 mg/day) was associated with a 53% reduction in the risk of developing breast cancer compared with low consumption (<3.7 mg/day) in a population-based case-control study of 608 premenopausal women over age 40 (Freudenheim et al 1996). Similar risk reductions were found in a nested case-control study of 540 New York women (Toniolo et al 2001) and another nested case-control study of 969 cases of breast cancer and matched controls from the Nurses' Health Study found that the risk of breast cancer was 25-35% less for women with the highest quintile compared with that for women with the lowest quintile of lutein/zeaxanthin and total carotenoid intake (Tamimi et al 2005). Although this association is encouraging, another study of 4697 women followed over 25 years found no significant relationships between lutein intake and breast cancer risk (Jarvinen et al 1997). Gastric cancer High serum lutein levels have been associated with a higher incidence of gastric carcinoma, according to a cohort study of 29,584 patients with oesophageal and stomach cancer (Abnet et al 2003); however, this association requires further investigation.

Bowel cancer The relationship between lutein and zeaxanthin intake and colon cancer is uncertain. A case-control study involving 1993 cases of colon cancer and 2410 controls found that lutein intake, as measured by a food frequency score, was inversely associated with colon cancer and another case-control study of 223 subjects with histologically confirmed colon or rectal cancer identified a non-significant inverse association with lutein (Levi et al 2000). A cohort analysis of 5629 women, however, found no such association (Terry et al 2002). More recently, a case-controlled study found that women with high intakes of long-chain polyunsaturated fatty acids had an inverse association between lutein and zeaxanthin intake and the risk of colon cancer risk (Nkondjock & Ghadirian 2004). Further investigation is required to clarify these findings because animal studies suggest low doses of lutein inhibit aberrant crypt foci formation, whereas high doses may increase the risk by 9-59% (Raju et al 2005). Prostate cancer Overall, epidemiological evidence suggests that lutein and zeaxanthin intake has no influence over the risk of prostate cancer (Bosetti et al 2004, Gann et al 1999, Giovannucci et al 1995, Huang et al 2003, Lu et al 2001, Nomura et al 1997, Schuurman et al 2002). However, when lutein was included as part of a mixed carotenoid and tocopherol extract, the combination was effective in an in vitro study of prostate cancer cell lines (Lu et al 2005) and a case-controlled study of 130 patients with adenocarcinoma of the prostate found that prostate cancer risk was seen to decline with increasing consumption of carotenoids, including lycopene,

alpha-carotene, beta-carotene, beta-cryptoxanthln, lutein and zeaxanthln (Jian et al 2005).

Laryngeal cancer A case-control study Involving 537 subjects identified an inverse relationship between dietary lutein and zeaxanthin intake, together with the intake of other carotenoids, and the risk of laryngeal cancer (Bidoli et al 2003).

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