**4.3 Alpha-carotene and beta-cryptoxanthin**

*Antioxidants*

**4.2 Lycopene**

as there was no association with prostate cancer risk [46]. However, there are studies that have reported an adverse rather than a protective effect of beta-carotene on prostate cancer. In the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) cohort study conducted in Japan among middle-aged men, the highest levels of serum beta-carotene resulted in a 2.29-fold (RR 2.29, 95% CI: 1.12–4.6; P = 0.023) higher risk of prostate cancer compared to participants with lowest levels of the antioxidant [50]. In the 18-year postintervention follow-up of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, beta-carotene increased the posttrial prostate cancer mortality (RR 1.20, 95% CI: 1.01–1.42) [15] (**Table 1**). Thus, the effect of beta-carotene remains inconclusive and may involve an adverse effect where high

Lycopene has been reported to possess more effective antioxidant properties compared to the carotenes and alpha-tocopherol [51]. Lycopene in the form of tomato-based products and to a lesser extent as a supplement is extensively studied with regards to risk of prostate cancer; however, the clinical evidence is inconclusive. In the prostate, lung, colorectal, and ovarian cancer screening trials, lycopene consumption decreased the risk of prostate cancer particularly in men with family history [52]. Similarly, in the Health Professionals Follow-Up Study, lycopene consumption was significantly associated with decreased prostate cancer risk (RR for high vs. low quintiles 0.84, 95% CI: 0.73–0.96; P = 0.003), and tomato sauce consumption had a greater reduction [53] (**Table 1**). Other prospective studies have reported that circulating levels of lycopene were inversely associated with highgrade prostate cancer (RR 0.55, 95% CI: 0.28–1.08) [39]; dietary intake of lycopene decreased the risk of lethal prostate cancer by lowering the degree of angiogenesis in the tumor [54], and lycopene consumption was associated with lower prostate

A number of meta-analysis sought to examine the efficacy of lycopene intake in primary prevention of prostate cancer. In a recent meta-analysis of 27 studies (22 were case studies), a statistically significant, though weak inverse association, was found between prostate cancer and lycopene [56]. In another systemic review and meta-analysis, circulating lycopene levels between 2.17 and 85 μg/dL were inversely associated with risk of prostate cancer; however, there was no linear association with levels greater than 85 μg/dL [57]. Further supporting evidence of the protective effect of lycopene intake was demonstrated in a recent meta-analysis of 42 studies where higher circulating and dietary lycopene levels were inversely associated with a 12% risk of prostate cancer but not with the advanced disease [58]. Other supporting evidence involves meta-analysis by Key et al. where lycopene though not associated with overall prostate cancer risk results in a 36% significantly lower risk with aggressive disease [21]; and a meta-analysis of 34 studies showed an association between reduced prostate cancer risk and dietary and blood lycopene levels [33]. Furthermore, Mariani et al. reported no overall benefit of decreasing the rate of high-grade prostatic intraepithelial neoplasia (HGPIN) progression from a

Possible pathways involving multiple mechanisms exist through which lycopene intake may reduce prostate cancer risk. Lycopene attenuates prostate cancer risk by modulating the expression of genes such as EGFR, CDK7, BCL2, and IGF-1R which are related to growth and survival [60]. Another study showed that lycopene increases the expression of BCO2, a tumor suppressor which mediates the inhibition of NF-κB signaling [61]. There is also evidence that lycopene can inhibit the proliferation of prostate cancer cell via PPARγLXRα-ABCA1 pathway [62]. Additionally,

serum concentrations may elevate prostate cancer risk and mortality.

cancer-specific mortality among men high-risk disease [55].

6-month lycopene supplementation [59].

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Other carotenoids such as alpha-carotene and that beta-cryptoxanthin have been investigated for possible association with prostate cancer risk. In a case control study, there was reduced risk of prostate cancer with lutein (OR 0.55, 95% CI: 0.37–0.81) and alpha-carotene (OR 0.67, 95% CI: 0.47–0.97) [66]. Nordström et al. found that circulating levels of alpha-carotene (RR 0.31, 95% CI: 0.15–0.63) were associated with decreased risk of prostate cancer [39]. Similarly, alpha-carotene intake was associated with decreased risk of prostate cancer (RR 0.87, 95% CI: 0.76–0.99) [33]. Further, a meta-analysis of 34 studies suggests that dietary alpha-carotene intake was associated with reduced risk of prostate cancer [14], and a study by Schuurman et al. showed similar findings for beta-cryptoxanthin [7].

However, in a case-control study conducted in Vietnam, there was no statistically significant association between prostate cancer risk and intake of alphacarotene, beta-cryptoxanthin, zeaxanthin, and lutein [44]. Similarly, in the Japan Collaborative Cohort study, dietary alpha-carotene intake was not associated with risk of prostate cancer [46]. The absence of the association of dietary intakes of lutein, beta-cryptoxanthin, and zeaxanthin with prostate cancer risk requires confirmation in future studies.
