**5.1 Coffee**

There are studies that have investigated the relationship between coffee consumption and risk of prostate cancer [55, 69–75]. There are those which have found an inverse relationship between coffee consumption and risk of prostate cancer [73–75]. The "Coffee Consumption and Prostate Cancer Risk Progression in Health Professionals Follow Up" report shows that there is a lower risk for prostate cancer

and significant association for reduced lethal and advanced cancer diagnosis in participants who consumed six or more cups of coffee per day. There was an inverse association for regular (each one cup per day increment: RR 0.94, P = 0.08) and decaffeinated coffee (RR 0.91, P = 0.05) [71].

In the Collaborative Prospective Cohort study conducted in the United Kingdom between 1970 and 1973 and followed up after 34 years, there was an inverse association between coffee consumption and risk of high-grade prostate cancer, but not the overall risk of the disease [70]. Notably, adjusting for social class and age, higher coffee consumption (three or more cups of coffee) was associated with significantly reduced risk of high Gleason grade prostate cancer compared with noncoffee drinkers [70]. Similarly, in a population cohort study, men with highest coffee consumption (>3 cups per day) had a 53% lower risk of prostate cancer compared with those with lower consumption (<2 cups per day) [72]. Another study supporting the potential beneficial effect of coffee consumption is a population-based case-control study reported by Russnes et al. where high coffee consumption (>6 cups per day) was associated with reduced risk of high grade (OR 0.45, 95% CI: 0.22–0.90; P < 0.05) and fatal prostate cancer [76]. In a recent population-based case-control study in a single institution in Italy, multivariate logistic regression demonstrated that both ferulic acid (OR 0.30, P < 0.05) and caffeic acid (OR 0.32, P < 0.05) were associated with decreased risk of prostate cancer, and higher dietary intake of the latter may be associated with reduced risk of the disease [67].

However, population-based study reported by Arab et al. using data from the North Carolina-Louisiana Prostate Cancer Project showed no association between decaffeinated or caffeinated coffee (4 cups per day) and highly aggressive prostate cancer (OR 0.92, 95% CI 0.61–1.39) [69] (**Table 2**). Similarly, in a most recent European study, there was no evidence of association for risk of total prostate cancer or cancer by grade, grade or fatality, and consumption of total, decaffeinated, or caffeinated coffee [77]. The findings of these studies bring attention to potential anticancer effect of polyphenols in coffee in reducing progression and metastasis of prostate cancer. However, some studies show no association with reduced nonlethal or advanced prostate cancer.

#### **5.2 Green tea**

Green tea (GT) is one of the most widely studied source of phenolic acids such epigallocatechin-3-gallate (EGCG), epicatechin-3-gallate (ECG), and epicatechin (EC). There are a number of studies that have investigated the relationship between risk of prostate cancer and green tea [78–82], and preclinical, clinical, and epidemiological data suggest that green tea catechins may reduce prostate cancer risk [83]. In a recent case-control study of Chinese men, epigallocatechin 3-gallate and green tea reduced the risk of prostate cancer; however, the authors indicated that these results should be replicated in larger cohort or case-control studies [84]. In a systematic review conducted by Cui et al., green tea catechins significantly decreased prostate cancer in high-grade prostatic intraepithelial patients (7.60 vs. 23.1%, RR 0.39, P = 0.044) [82]. In another systematic review and meta-analysis study involving three randomized controlled trials and seven observational studies, there was a linear association between green tea catechins consumption (>7 cups per day) and risk of prostate cancer [78].

There is further evidence of the chemopreventative effect of green tea. In a recent case-control involving Vietnamese men, increasing tea consumption (>500 ml/day) was found to be associated with decreased risk of prostate cancer [84]. Similar findings were reported in a case-control study of Algerian men, although the results were borderline statistically [80]. In one of the first clinical

**227**

group [86].

fatality [77].

*Dietary Antioxidants in the Chemoprevention of Prostate Cancer*

**Year of study**

2012 Tea (>7 cups/

2011 Coffee (>6 cups/

2019 Coffee (375 ml/

2016 Coffee (6 cups/

2006 Green tea (> 5

2012 Coffee (>4 cups/

2014 Coffee

*RR = relative risk, CI = confidence interval, P.R.E = percentage relative effect, Sel. Sup = selenium supplement.*

day)

day)

day) Green tea (106 ml/day)

day)

cups/day)

day)

(moderate)

**Sample RR 95% CI P.R.E** 

HR = 1.02 HR = 0.98

2017 Green tea OR = 0.60 0.37–0.98 40%

HR = 1.50 1.06–2.12 50%

RR = 0.82 0.68–0.98 18%

OR = 0.45 0.22–0.90 55%

HR = 0.85 0.50–1.43 15%

OR = 0.92 0.61–1.39 8%

RR = 0.92 0.85–1.00 8%

0.93–1.27 0.90–1.07 **outcome**

2% 2%

studies to examine the effect of polyphenols (from green tea) on prostate cancer, Betuzzi and colleagues showed that green tea consumption reduces the incidence of prostate cancer in men with high-grade prostate intraepithelial neoplasia (HGPIN). HGPIN is the most likely precursor to prostate cancer, and this study demonstrated that 30% of men with HGPIN would develop prostate cancer 1 year after biopsy [85]. In this double-blind placebo-control study, the green tea consumption group had a 3% incidence rate, while the placebo-treated group had 30% [85]. In a followup study by the same authors 2 years later, men in the green tea consumption group had lower incidence of prostate cancer compared with those in the nontreatment

There have being inconsistent results that do exist with regards to the chemopreventive capacity of green tea. For instance, one study showed a decreased risk of prostate cancer in a multisite case-control study in which participants consumed two cups or more of tea per day [87]. In another study, no association between tea consumption and prostate cancer risk was found [88]. In both studies, there was no association with prostate cancer and coffee consumption. In a large cohort European Study reported by Sen and colleagues, no association was observed for tea consumption and risk of prostate cancer by grade, stage, or

Initially, polyphenols were thought to eliminate cancer cells only through direct radical scavenging in a random manner. However, they were found to have moderate efficiency in this function, inferring that more complex action must be at work

*DOI: http://dx.doi.org/10.5772/intechopen.85770*

**author(s)**

Shafique et al. [70]

Wilson et al. [71]

Sen et al. [77]

Russnes et al. [76]

Lee et al. [81]

Kikuchi et al. [88]

Arab et al. [69]

Zong et al. [74]

*Showing studies on the effect of coffee and green tea on prostate cancer.*

**Method Name of** 

Cohort

Case-control

Observational

Meta-analysis

**Table 2.**


#### *Dietary Antioxidants in the Chemoprevention of Prostate Cancer DOI: http://dx.doi.org/10.5772/intechopen.85770*

#### **Table 2.**

*Antioxidants*

and significant association for reduced lethal and advanced cancer diagnosis in participants who consumed six or more cups of coffee per day. There was an inverse association for regular (each one cup per day increment: RR 0.94, P = 0.08) and

In the Collaborative Prospective Cohort study conducted in the United Kingdom between 1970 and 1973 and followed up after 34 years, there was an inverse association between coffee consumption and risk of high-grade prostate cancer, but not the overall risk of the disease [70]. Notably, adjusting for social class and age, higher coffee consumption (three or more cups of coffee) was associated with significantly reduced risk of high Gleason grade prostate cancer compared with noncoffee drinkers [70]. Similarly, in a population cohort study, men with highest coffee consumption (>3 cups per day) had a 53% lower risk of prostate cancer compared with those with lower consumption (<2 cups per day) [72]. Another study supporting the potential beneficial effect of coffee consumption is a population-based case-control study reported by Russnes et al. where high coffee consumption (>6 cups per day) was associated with reduced risk of high grade (OR 0.45, 95% CI: 0.22–0.90; P < 0.05) and fatal prostate cancer [76]. In a recent population-based case-control study in a single institution in Italy, multivariate logistic regression demonstrated that both ferulic acid (OR 0.30, P < 0.05) and caffeic acid (OR 0.32, P < 0.05) were associated with decreased risk of prostate cancer, and higher dietary intake of the

However, population-based study reported by Arab et al. using data from the North Carolina-Louisiana Prostate Cancer Project showed no association between decaffeinated or caffeinated coffee (4 cups per day) and highly aggressive prostate cancer (OR 0.92, 95% CI 0.61–1.39) [69] (**Table 2**). Similarly, in a most recent European study, there was no evidence of association for risk of total prostate cancer or cancer by grade, grade or fatality, and consumption of total, decaffeinated, or caffeinated coffee [77]. The findings of these studies bring attention to potential anticancer effect of polyphenols in coffee in reducing progression and metastasis of prostate cancer. However, some studies show no association with reduced nonlethal

Green tea (GT) is one of the most widely studied source of phenolic acids such epigallocatechin-3-gallate (EGCG), epicatechin-3-gallate (ECG), and epicatechin (EC). There are a number of studies that have investigated the relationship between risk of prostate cancer and green tea [78–82], and preclinical, clinical, and epidemiological data suggest that green tea catechins may reduce prostate cancer risk [83]. In a recent case-control study of Chinese men, epigallocatechin 3-gallate and green tea reduced the risk of prostate cancer; however, the authors indicated that these results should be replicated in larger cohort or case-control studies [84]. In a systematic review conducted by Cui et al., green tea catechins significantly decreased prostate cancer in high-grade prostatic intraepithelial patients (7.60 vs. 23.1%, RR 0.39, P = 0.044) [82]. In another systematic review and meta-analysis study involving three randomized controlled trials and seven observational studies, there was a linear association between green tea catechins consumption (>7 cups

There is further evidence of the chemopreventative effect of green tea. In a recent case-control involving Vietnamese men, increasing tea consumption (>500 ml/day) was found to be associated with decreased risk of prostate cancer [84]. Similar findings were reported in a case-control study of Algerian men, although the results were borderline statistically [80]. In one of the first clinical

decaffeinated coffee (RR 0.91, P = 0.05) [71].

latter may be associated with reduced risk of the disease [67].

or advanced prostate cancer.

per day) and risk of prostate cancer [78].

**5.2 Green tea**

**226**

*Showing studies on the effect of coffee and green tea on prostate cancer.*

studies to examine the effect of polyphenols (from green tea) on prostate cancer, Betuzzi and colleagues showed that green tea consumption reduces the incidence of prostate cancer in men with high-grade prostate intraepithelial neoplasia (HGPIN). HGPIN is the most likely precursor to prostate cancer, and this study demonstrated that 30% of men with HGPIN would develop prostate cancer 1 year after biopsy [85]. In this double-blind placebo-control study, the green tea consumption group had a 3% incidence rate, while the placebo-treated group had 30% [85]. In a followup study by the same authors 2 years later, men in the green tea consumption group had lower incidence of prostate cancer compared with those in the nontreatment group [86].

There have being inconsistent results that do exist with regards to the chemopreventive capacity of green tea. For instance, one study showed a decreased risk of prostate cancer in a multisite case-control study in which participants consumed two cups or more of tea per day [87]. In another study, no association between tea consumption and prostate cancer risk was found [88]. In both studies, there was no association with prostate cancer and coffee consumption. In a large cohort European Study reported by Sen and colleagues, no association was observed for tea consumption and risk of prostate cancer by grade, stage, or fatality [77].

Initially, polyphenols were thought to eliminate cancer cells only through direct radical scavenging in a random manner. However, they were found to have moderate efficiency in this function, inferring that more complex action must be at work

in eliminating cancer cells. Further investigations proved that polyphenols employ biological methods in providing cancer prevention and even elimination, such as binding to multiple cellular proteins and regulating signal transduction. Alterations in signal pathways affect multiple processes that hinder cancer initiation, progression, and metastasis [89]. Among green tea catechins, epigallocatechin-3-gallate (EGCG) is widely investigated for its cancer preventive properties. In a recent study, the difluoro analog, called (-)-5,7-difluoro-epicatechin-3-O-gallate and (-)-epicatechin-3-O-gallate from green tea dose-dependently, inhibits tumorigenesis during initiation, promotion, and progression in low-metastatic LNCaP and high-metastatic PC-3 prostate cancer cells [90]. There is also recent evidence that green tea catechins contribute to the inhibition of prostate carcinogenesis by modifying miRNA expression and their target mRNAs, as well as acting as epigenetic modulators [91]. Epicatechin-3-O-gallate and theaflavins have been found to reduce the rate of cell growth in DU 145 human prostate cancer cells [92]. The inhibition of proliferation in the human prostate cancer DU145 cells by tea polyphenols may be associated with reduction in the expression of the surviving gene [93].

The extensive methylation of green tea polyphenols and low bioavailability limits their chemopreventive activity. A combination of green tea polyphenols and a methylation inhibitor quercetin inhibit growth and proliferation in androgensensitive LAPC-4 prostate cancer cells. There was also evidence of stimulation of apoptosis and inhibition of phosphatidylinositol 3-kinase/Akt signaling [14]. More in-depth studies have demonstrated that green tea polyphenols induced p53-dependent and p53-independent apoptosis in human prostate cancer LNCaP cells by two distinct pathways. One pathway involved the inhibition of the survival pathway where there is Akt deactivation and loss of BAD phosphorylation, while in the other, there is FAS upregulation via activation of c-jun-N-terminal kinase resulted in caspase-8 activation, FADD phosphorylation, and truncation of BID [94]. There is documentation of other molecular mechanisms by which green tea polyphenols trigger death and apoptosis of human prostate cancer cells via inhibition histone deacetylase, irrespective of their p53 status [6].
