Intakes of Fruits, Vegetables, Vitamins A, C, and E, and Carotenoids and Risk of Renal Cell Cancer

Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 01/2007; 15(12):2445-52. DOI: 10.1158/1055-9965.EPI-06-0553
Source: PubMed


Fruits and vegetables rich in antioxidants have been proposed to reduce the risk of renal cell cancer. However, few prospective studies have examined the intakes of fruits, vegetables, and antioxidant vitamins in relation to the risk of renal cell cancer.
We prospectively examined the associations between the intakes of fruits, vegetables, vitamins A, C, and E, and carotenoids and risk of renal cell cancer in women and men. We followed 88,759 women in the Nurses' Health Study from 1980 to 2000, and 47,828 men in the Health Professionals Follow-up Study from 1986 to 2000. We assessed dietary intake every 2 to 4 years using a validated semiquantitative food frequency questionnaire. The Cox proportional hazards model was used to estimate study-specific multivariate relative risks (RR), which were pooled using a random effects model.
A total of 248 (132 women and 116 men) incident renal cell cancer cases were ascertained during 2,316,525 person-years of follow-up. The consumption of fruits and vegetables was associated with a decreased risk of renal cell cancer in men (multivariate RR, 0.45; 95% CI, 0.25-0.81, for >or=6 servings of fruit and vegetable intake/d versus <3 servings/d; P test for trend = 0.02), but not in women (multivariate RR, 1.17; 95% CI, 0.66-2.07, for the same contrast; P test for trend = 0.25; P test for between-studies heterogeneity = 0.02). Intakes of vitamins A and C from food and carotenoids were inversely associated with the risk of renal cell cancer in men only, but we cannot exclude the possibility that this was due to other factors in fruit and vegetables. No clear association was observed for vitamin E in women or men.
Fruit and vegetable consumption may reduce the risk of renal cell cancer in men.

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    • "For example, no association was found between fruit and vegetable consumption and a reduction in the risk of bladder cancer [2]. In addition, Lee et al. reported reduced risk of renal cell cancer in men but no clear association in women [3]. Carotenoids, a major phytonutrient component of diets rich in fruits and vegetables, have been suggested to have a cancer preventive effect [4] [5]. "
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    ABSTRACT: Aberrant activation of the Nuclear Factor Kappa B (NFkB) transcription system contributes to cancer progression, and has a harmful effect on bone health. Several major components of the NFkB pathway, such as IkB Kinase (IKK) and the NFkB subunits contain cysteine residues that are critical for their activity. The interaction of electrophiles with these cysteine residues results in NFkB inhibition. Carotenoids, hydrophobic plant pigments, are devoid of electrophilic groups, and we have previously demonstrated that carotenoid derivatives, but not the native compounds activate the Nrf2 transcription system. The aim of the current study was to examine whether carotenoid derivatives inhibit NFkB, and, if so, to determine the molecular mechanism underpinning the inhibitory action. We report in the present study that a mixture of oxidized derivatives, prepared by ethanol extraction from partially oxidized lycopene preparation, inhibited NFkB reporter gene activity: In contrast, the intact carotenoid was inactive. A series of synthetic dialdehyde carotenoid derivatives inhibited reporter activity as well as several stages of the NFkB pathway in both cancer and bone cells. The activity of the carotenoid derivatives depended on the reactivity of the electrophilic groups in reactions such as Michael addition to sulphydryl groups of proteins. Specifically, carotenoid derivatives directly interacted with two key proteins of the NFkB pathway: The IKKβ, and the p65 subunit. Direct interaction with IKKβ was found in an in-vitro kinase assay with a recombinant enzyme. The inhibition by carotenoid derivatives of p65 transcriptional activity was observed in a reporter gene assay performed in the presence of excess p65. This inhibition action resulted, at least in part, from direct interaction of the carotenoid derivative with p65 leading to reduced binding of the protein to DNA as evidenced by electrophoretic mobility shift assay (EMSA) experiments. Importantly, we found by using mutation in key cysteine residues of both p65 and IKK that specific thiol groups are essential for NFkB inhibition by carotenoid derivatives. In conclusion, we propose that electrophilic carotenoid derivatives contribute to cancer prevention as well as bone health maintenance via the inhibition of the NFkB transcription system: Pivotal thiol groups of both IKK and p65 play a key role in this process.
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    • "Despite associations with diet-related chronic conditions, such as obesity, hypertension, and diabetes, dietary risk factors for RCC are not well established (World Cancer Research Fund/American Institute for Cancer Research, 2007; Chow et al, 2010). Intake of fruits and vegetables may lower RCC risk (Rashidkhani et al, 2005; Lee et al, 2006), whereas high meat intake may increase risk (Faramawi et al, 2007; Aune et al, 2009; Dolwick Grieb et al, 2009), but the epidemiological evidence for various aspects of diet is largely inconsistent. "
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    • "For example, no association was found between fruit and vegetable consumption and a reduction in the risk of bladder cancer [2]. In addition, Lee et al. reported reduced risk of renal cell cancer in men but no clear association in women [3]. Carotenoids, a major phytonutrient component of diets rich in fruits and vegetables, have been suggested to have a cancer preventive effect [4] [5]. "
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