2. Kidney Cancer
Kidney cancer is a broad term used to describe a heterogeneous group of tumors from a histological point of view. Kidney cancer can develop from renal parenchyma or the renal collecting system. Renal cell carcinoma (RCC) arises from renal parenchyma epithelial cells and accounts for approximately 90% of kidney cancer cases. RCC accounts for around 3% of all cancers, with the highest incidence reported in Western countries [
11]. The most common histological type of RCC is clear cell RCC, which represents ~80% of RCCs. Among the other histological subtypes of kidney cancer, papillary (~10%) and chromophobe (~5%) are the most common. Clear cell and papillary RCCs stem from the epithelial cells of the proximal tubule. Chromophobe RCC is thought to arise from the epithelium of the collecting tubule [
69]. Well-established risk factors include smoking, obesity, hypertension, and diabetes [
70]. Carotenoids, as potent antioxidants, may influence RCC risk.
Recently, Sahin et al. conducted a very interesting experimental study to examine the role of a lycopene-rich diet in the development of RCC in the tuberous sclerosis 2 (TSC2) mutant Eker rat model. Eker rats develop spontaneous renal tumors and leiomyoma, which may be due to tuberous sclerosis 2 (TSC2) mutation resulting in the activation of the mammalian target of the rapamycin (mTOR) pathway. Eker rats received 0, 100, or 200 mg/kg of lycopene as part of their diet. After 18 months, the mean numbers of renal carcinomas were statistically significantly decreased in the lycopene-treated rats (
p < 0.008) when compared with the untreated controls. Tumor numbers decreased linearly as the daily lycopene increased from 0 to 200, suggesting a role of lycopene in the prevention of RCC [
71].
Bock et al. recently published the results of the U.S. Kidney Cancer Study, which was a population-based case–control study. Clear, significant inverse associations with RCC risk were found for α-carotene, β-carotene, lutein, zeaxanthin, and lycopene after adjusting for all variables [
72].
In another case–control study conducted on 1138 histologically confirmed cases of RCC, Hu et al. showed a significant reduction in RCC risk, with ORs of 0.74 and 0.77 for the highest versus the lowest quartiles for β-carotene and lutein/zeaxanthin. This relationship was more pronounced in women, obese, and ever smoking individuals [
73]. Two other case–control studies supported a significant protective influence of carotenoids on RCC risk [
74,
75]. However, a case–control study by Bosetti et al. did not show any protective impact of carotenoid intake and RCC risk [
76].
The Women’s Health Initiative (WHI) was a prospective cohort study that included 96,196 postmenopausal women who were followed for up to 12 years.
There were 240 cases of RCC diagnosed during follow-up. Lycopene intake was inversely correlated with RCC risk. Individuals with the highest quartile of intake had a 39% lower risk of RCC compared with those in the lowest quartile. Interestingly, none of the other evaluated carotenoids (dietary β-carotene, α-carotene, β-cryptoxanthin, and lutein plus zeaxanthin) showed any significant association [
77].
On the other hand, a prospective cohort study with 88,759 women and 47,828 men did not show a significant influence of lycopene on RCC risk, although it did find significant correlations for β-carotene, α-carotene, β-cryptoxanthin, and lutein plus zeaxanthin [
78]. It was shown in the ATBC prospective study that neither lycopene nor other carotenoid intake was correlated with RCC risk [
79], and this confirmed other cohort studies that showed null associations between carotenoids and RCC [
80,
81].
In 2009, Lee published a pooled cohort analysis of 13 prospective studies that included 1478 cases of RCC among 530,469 women and 244,483 men, who were followed for up to 7 to 20 years. It showed that increased vegetable and fruit consumption was associated with a decreased risk of RCC. Among the specific carotenoids they observed, there was an 18% lower risk of RCC when comparing the highest and lowest quintiles of β-carotene intake. There was a similar trend for other carotenoids (α-carotene, β-cryptoxanthin, and lutein/zeaxanthin) [
82].
Zhang et al. recently published a meta-analysis that encompassed 19 observational studies (5 cohort and 14 case–control) with 10,215 RCC cases, summarizing current evidence from epidemiological data on the topic of fruit and vegetables and RCC risk. Although they did not examine carotenoid intake in their work, they found significant reductions in RCC risk for the highest versus the lowest intake of vegetables and fruit (RR = 0.73 and 0.86 respectively) [
83]. It can only be speculated that carotenoids were at least partially responsible for the observed effect.