Our findings are consistent with many other prospective studies that have reported no association between increased fruit and vegetable consumption and RCC risk23–28
. Case-control studies have yielded more conflicting findings 6–9, 13–15, 29–33
. In contrast to most reports, a study that combined data from the Nurses’ Health Study and the Health Professionals Follow-up Study and included a total of 248 RCC cases showed that higher fruit and vegetable consumption was associated with a significantly reduced risk of RCC in men (RR and 95% CI for ≥6 versus < 3 servings per day = 0.45 (0.25–0.81)), but not in women 10
. Furthermore, there was an interaction with smoking status such that the protective effect was only evident in nonsmoking males. Our cohort was comprised exclusively of smokers, which might have precluded the detection of any modest yet beneficial effects of fruit and vegetable intake on RCC risk.
It is unclear why beneficial associations between fruit and vegetable intake and RCC risk were observed in younger but not older men in our cohort. Our study is not the first to demonstrate such a finding; in a case-control study conducted in Italy, Galeone et al. noted a significant inverse association between vegetable fibre intake and RCC risk in subjects < 60 years of age, with no such relation apparent in older individuals 34
. We are not aware of any heterogeneity in the biology of RCC across age subgroups. While such differences may indeed exist, it is more likely that our finding is due to chance.
Although oxidative stress appears to play a role in the development of RCC 12
, antioxidants have been inconsistently related to RCC in past prospective and case-control studies6–10, 13–16, 35, 36
. Most of these studies investigated α-tocopherol, vitamin C, and individual carotenoids, but did not examine flavonoids or combinations of individual antioxidant nutrients. We found no evidence for a protective effect of any antioxidant nutrient on RCC risk.
Strengths of our study include its prospective design, which limits recall bias, use of a validated dietary questionnaire that was created specifically for the ATBC study, availability of pre-randomization serum β-carotene, retinol, and α-tocopherol concentrations for virtually all participants, the large number of incident RCC cases, and our ability to control for a large number of important confounders.
A possible limitation is that our results may not be generalizable to females, nonsmokers, or non-White ethnicities. We also relied on a single measure of dietary intake and serum nutrient concentrations, which may not adequately reflect lifetime dietary habits. In addition, FFQs may only be valid when asking about food intake over the past few days; when compared to food records or 24 hour recalls, their validity can be somewhat poor, especially for energy intake 37
. The correlation coefficients in our study, however, ranged between 0.50 and 0.76 for individual antioxidants, suggesting good agreement between data from the FFQ and food consumption records. Random misclassification in FFQ data could have biased our results toward the null, especially if the true association between fruits, vegetables, and or antioxidant nutrients and RCC risk was modest.
In conclusion, our results suggest that increased consumption of fruit, vegetables, and antioxidant nutrients does not reduce the risk of RCC in adult male smokers, although the lack of effect in our study may be partially attributable to misclassification of dietary intakes associated with the use of FFQs. Future studies should continue to address whether higher intakes of plant foods and antioxidants might be beneficial for RCC in nonsmokers, women, and diverse racial populations.