No association between fruit, vegetables, antioxidant nutrients and risk of renal cell carcinoma

Abstract

Previous epidemiologic studies that have examined the relationship between renal cell carcinoma (RCC) risk and intakes of plant foods and antioxidant nutrients have yielded inconsistent results. We therefore examined the associations between intakes of fruit, vegetables, carotenoids, flavonoids, vitamin E and vitamin C and RCC risk in the Alpha-Tocopherol, BetaCarotene Cancer Prevention (ATBC) Study cohort. At baseline, 27,062 male Finnish smokers aged 50-69 years completed a 276-item dietary questionnaire that included questions on frequency of consumption and portion size. During up to 19 years of follow-up, 255 men developed RCC. Cox proportional hazards models were utilized to estimate relative risks (RR) and 95% confidence intervals (CI). Despite a large range in intake, no association was observed between fruit, vegetables or antioxidant nutrients and RCC risk. For example, multivariate RRs and 95% CIs for the highest versus the lowest quartile of intake were 0.79 (0.55-1.14), 1.23 (0.85-1.79), 1.09 (0.74-1.60), 0.83 (0.57-1.21), 1.09 (0.73-1.64) and 0.99 (0.67-1.46) for fruit, vegetables, total carotenoids, total flavonoids, total vitamin E and vitamin C, respectively (all p values for trend > 0.05). Our results indicate that diet may not play a large role in the etiology of RCC in male smokers, although further examination of these associations in nonsmokers, women and diverse racial populations is warranted.The incidence of renal cell carcinoma (RCC) is increasing both in the United States and globally.1,2 The rise in incidence is due in part to more frequent use of ultrasonography, computed tomography, and magnetic resonance imaging, which inadvertently detect kidney cancers.3 However, the incidence of advanced and metastatic disease has also increased, suggesting that the rise is not entirely due to earlier detection. 2Established risk factors for RCC include age, race, gender, smoking and obesity, with most studies also demonstrating a positive association with hypertension.2,4 Dietary factors also appear to play a role, with higher fruit and vegetable intake linked to lower risks of this disease in several studies. 5-10Fruits and vegetables are rich sources of free-radical scavenging antioxidant nutrients, including carotenoids, flavonoids, and vitamin C. Vitamin E is also a powerful antioxidant, although its major food sources are not fruits and vegetables. Rather, vitamin E is found predominantly in vegetable oils and nuts.11 Because oxidative stress is hypothesized to play a role in the development of RCC, 12 higher dietary intakes and/or blood levels of these nutrients may protect against the initiation and progression of this malignancy. Studies that have examined the relationship between RCC and individual antioxidant nutrients, however, have yielded inconsistent results. 6,7,9,10,[13][14][15][16] We investigated associations of fruits, vegetables and individual antioxidant nutrients with subsequent risk of RCC in a large cohort study of male smokers. With 255 incident RCC cases available for ...

Renal cell carcinoma risk associated with lower intake of micronutrients

“…Aligned with our observations, previous case‐control,6, 34 individual cohort21 and pooled cohort22 studies have demonstrated significant associations between intake of carotenoids and RCC risk 34, 35, 36. However, other case‐control37 and cohort5, 7, 8, 14, 23 studies did not detect an association. Reasons for discrepancies in findings among dietary risk factor studies may be due to differences in the source populations, variations in dietary assessment methods, and varying degrees of recall bias between studies.…”

“…Aligned with these observations, previous studies demonstrated an association between increased intake of tocopherols with decreasing RCC risk for males and females, nonsmokers, and ever smokers 5, 36, 37, 38, 39, 40. In contrast, other studies reported associations of marginal or no significance between RCC risk and tocopherol intake 7, 8, 10, 14, 15, 41…”

“…Racial differences in the distribution of several of these risk factors likely account for some of the excess risk observed in AA as compared to EA populations 4, 12, 13. Many vitamins from diet and supplements, including vitamin A, C, and B, have been shown to have antioxidative effects and may influence RCC risk 5, 6, 7, 8, 14, 15. Intake of dietary E vitamins, including α‐, β‐, δ‐, and γ‐tocopherol, is suggested to be chemo‐preventative 16.…”

“…Diets rich in carotenoids, including α‐carotene, β‐carotene, β‐cryptoxanthin, lutein zeaxanthin, and lycopene, have been associated with lower RCC risk 6, 21, 22, 23. Several studies, however, have demonstrated no significant relationship between micronutrient intake and RCC 7, 14, 15. These discrepancies in the literature highlight the importance of further exploration of the role of micronutrients in RCC risk.…”

Metabolic features of clear-cell renal cell carcinoma: mechanisms and clinical implications

“…73 Conversely, no association between dietary intake of fruits, vegetables, carotenoids, flavonoids, vitamin E, and vitamin C and the risk of developing RCC was found in the ATBC (AlphaTocopherol, Beta-Carotene Cancer Prevention) study (27 062 male Finnish smokers, 255 cases followed up for 19 years). 74 Similarly, in the NLCS (Netherlands Cohort Study) on diet and cancer, van Dijk and colleagues reported no association between carotenoid, vitamin or supplemental vitamin intake and the risk of RCC. 75 Thus, although metabolic alterations in oxidative stress pathways and fat metabolism are definitely part of the RCC genotype and phenotype, the available data do not support a role for dietary manipulations in altering the risk of developing RCC.…”