Effect of Carotene and Lycopene on the Risk of Prostate Cancer: A Systematic Review and Dose-Response Meta-Analysis of Observational Studies

Background

Many epidemiologic studies have investigated the association between carotenoids intake and risk of Prostate cancer (PCa). However, results have been inconclusive.

Methods

We conducted a systematic review and dose-response meta-analysis of dietary intake or blood concentrations of carotenoids in relation to PCa risk. We summarized the data from 34 eligible studies (10 cohort, 11 nested case-control and 13 case-control studies) and estimated summary Risk Ratios (RRs) and 95% confidence intervals (CIs) using random-effects models.

Results

Neither dietary β-carotene intake nor its blood levels was associated with reduced PCa risk. Dietary α-carotene intake and lycopene consumption (both dietary intake and its blood levels) were all associated with reduced risk of PCa (RR for dietary α-carotene intake: 0.87, 95%CI: 0.76–0.99; RR for dietary lycopene intake: 0.86, 95%CI: 0.75–0.98; RR for blood lycopene levels: 0.81, 95%CI: 0.69–0.96). However, neither blood α-carotene levels nor blood lycopene levels could reduce the risk of advanced PCa. Dose-response analysis indicated that risk of PCa was reduced by 2% per 0.2mg/day (95%CI: 0.96–0.99) increment of dietary α-carotene intake or 3% per 1mg/day (95%CI: 0.94–0.99) increment of dietary lycopene intake.

Conclusions

α-carotene and lycopene, but not β-carotene, were inversely associated with the risk of PCa. However, both α-carotene and lycopene could not lower the risk of advanced PCa.     

Chemistry,distribution, and metabolism of tomato carotenoids and their impact on human health

Recent epidemiological studies have suggested that the consumption of tomatoes and tomato-based food products reduce the risk of prostate cancer in humans. This protective effect has been attributed to carotenoids, which are one of the major classes of phytochemicals in this fruit. The most abundant carotenoid in tomato is lycopene, followed by phytoene, phytofluene, zeta-carotene, gamma-carotene, beta-carotene, neurosporene, and lutein. The distribution of lycopene and related carotenoids in tomatoes and tomato-based food products has been determined by extraction and high-performance liquid chromatography-UV/Visible photodiode array detection. Detailed qualitative and quantitative analysis of human serum, milk, and organs, particularly prostate, have revealed the presence of all the aforementioned carotenoids in biologically significant concentrations. Two oxidative metabolites of lycopene, 2,6-cyclolycopene-1,5-diols A and B, which are only present in tomatoes in extremely low concentrations, have been isolated and identified in human serum, milk, organs (liver, lung, breast, liver, prostate, colon) and skin. Carotenoids may also play an important role in the prevention of age-related macular degeneration, cataracts, and other blinding disorders. Among 25 dietary carotenoids and nine metabolites routinely found in human serum, mainly (3R,3'R,6'R)-lutein, (3R,3'R)-zeaxanthin, lycopene, and their metabolites were detected in ocular tissues. In this review we identified and quantified the complete spectrum of carotenoids from pooled human retinal pigment epithelium, ciliary body, iris, lens, and in the uveal tract and in other tissues of the human eye to gain a better insight into the metabolic pathways of ocular carotenoids. Although (3R,3'R,6'R)-lutein, (3R,3'R)-zeaxanthin, and their metabolites constitute the major carotenoids in human ocular tissues, lycopene and a wide range of dietary carotenoids have been detected in high concentrations in ciliary body and retinal pigment epithelium. The possible role of lycopene and other dietary carotenoids in the prevention of age-related macular degeneration and other eye diseases is discussed.     

Dietary intake of carotenoids and retinol and the risk of acute myocardial infarction in Italy

BACKGROUND: Carotenoids may reduce the risk of coronary heart disease through their antioxidant properties, but the results of epidemiological studies are controversial. We analysed the relation between the intake of selected carotenoids and retinol and risk of acute myocardial infarction (AMI). METHODS: A case-control study was conducted in Milan, Italy, in 1995-2003. Cases were 760 patients with nonfatal AMI, and controls 682 patients admitted to hospital. RESULTS: The risk of AMI decreased with increasing intake of alpha-carotene (odds ratios, OR = 0.71, 95% confidence intervals, CI 0.51-0.98, for the highest vs the lowest quartile of intake), beta-carotene (OR = 0.71, 95% CI 0.50-1.01) and beta-criptoxanthin (OR = 0.64, 95% CI 0.46-0.88). No associations emerged for total carotenoids, lycopene, lutein plus zeaxanthin and retinol. CONCLUSIONS: Our study suggests a weak protective effect of alpha-carotene, beta-carotene and beta-criptoxanthin on the risk of AMI. It also indicates that total carotenoids, lycopene, lutein plus zeaxanthin and retinol were not related to the risk of the disease.     

Green tea consumption, genetic susceptibility, PAH-rich smoky coal, and the risk of lung cancer

Experimental evidence suggests that green tea (Camellia sinesis) may reduce the risk of lung cancer through several hypothesized mechanisms including scavenging oxidative radicals, inhibition of tumor initiation, and modulation of detoxification enzymes. However, epidemiologic results have not been consistent as to the relationship between green tea consumption and lung caner prevention. We employed a population-based case-control study of 122 cases and 122 controls to investigate the effect that green tea consumption may have on the risk of lung cancer and whether polymorphisms in 8-oxoguanine-DNA glycosylase (OGG1), glutathione-S-transferase M1 (GSTM1), and aldo-keto reductase 1C3 (AKR1C3) modify such an association. Daily green tea consumption was associated with a non-significant reduction in lung cancer risk. However, the effect of smoky coal exposure was higher for non-drinkers (odds ratio (OR)=4.93; 95% confidence interval (95% CI)=1.27-19.13) than for drinkers (OR=1.88; 95% CI=1.01-3.48). Further, among individuals with the OGG1 Cys(326) allele, daily consumption was associated with a 72% reduction (95% CI=0.09-0.94). Among GSTM1 null homozygotes, those who consumed green tea daily had a non-significant reduction in risk compared with non-consumers. Green tea consumption had no effect among OGG1 Ser(326) homozygotes or GSTM1 carriers. In addition, AKR1C3 genotype did not modulate the effect of green tea consumption. The chemopreventive effects of green tea in this population may be restricted to individuals who are particularly susceptible to oxidative stress and oxidative DNA damage.     

Lycopene and beta-carotene protect against oxidative damage in HT29 cells at low concentrations but rapidly lose this capacity at higher doses

Epidemiological studies have clearly demonstrated a link between dietary carotenoids and the reduced incidence of certain diseases, including some cancers. However recent intervention studies (e.g. ATBC, CARET and others) have shown that beta-carotene supplementation has little or no beneficial effect and may, in fact, increase the incidence of lung cancers in smokers. This presents a serious dilemma for the scientific community - are carotenoids at high concentrations actually harmful in certain circumstances? Currently, a significant number of intervention studies are on-going throughout the world involving carotenoids (of both natural and synthetic origin). Our approach has been to study the ability of supplementary carotenoids in protecting cells against oxidatively-induced DNA damage (as measured by the comet assay), and membrane integrity (as measured by ethidium bromide uptake). Both lycopene and beta-carotene only afforded protection against DNA damage (induced by xanthine/xanthine oxidase) at relatively low concentrations (1-3 microM). These levels are comparable with those seen in the plasma of individuals who consume a carotenoid-rich diet. However, at higher concentrations (4-10 microM), the ability to protect the cell against such oxidative damage was rapidly lost and, indeed, the presence of carotenoids may actually serve to increase the extent of DNA damage. Similar data were obtained when protection against membrane damage was studied. This would suggest that supplementation with individual carotenoids to significantly elevate blood and tissue levels is of little benefit and, may, in fact, be deleterious. This in vitro data presented maybe significant in the light of recent intervention trials.     

Lycopene inhibits DNA damage and liver necrosis in rats treated with ferric nitrilotriacetate.

Experimental and epidemiological evidence suggests that lycopene, a carotenoid present in tomatoes, tomato products, and several fruits and vegetables, may play a role in preventing certain cancers in humans. We have investigated the effect of lycopene pretreatment on lipid peroxidation, oxidative damage to DNA, and histopathological changes in liver of animals subjected to intraperitoneal (ip) ferric nitrilotriacetate (Fe-NTA) administration. Compared with control rats, liver of Fe-NTA-treated animals showed a significant increase in the 8-oxo-7,8-dihydro-2'-deoxyguanosine level and a 75% increase in malondialdehyde accumulation concomitant with histopathological changes. Five days of lycopene pretreatment (10 mg/kg body weight, ip) almost completely prevented liver biomolecule oxidative damage and protected the tissue against the observed histological alterations.     

Lycopene and heart health

Cardiovascular diseases (CVDs) are the leading causes of human morbidity and mortality in developed countries. Specific biomarkers in this context are markers of inflammation, lipid status, thrombosis and oxidative stress. One recommendation for CVD prevention is to increase consumption of fruits and vegetables as good sources of secondary plant products, e.g. carotenoids. This review aimed to show linkages between lycopene, one main carotenoid in the human diet, and prevention of heart diseases by looking for epidemiological data, results from in vitro experiments and results from in vivo studies (animal studies and human intervention trials). In addition, patents and products within the context of lycopene and CVD prevention will be discussed with a special emphasis on health claims. Epidemiological data, in vitro data and results from animal experiments partly showed promising preventive mechanisms of lycopene. In contrast, until now, human intervention studies mostly failed to show any CVD prevention. However, there is still an encouraging situation, giving hints for antioxidant as well as anti-inflammatory effects of lycopene. These mechanisms could be the background for cardio-protective effects of tomatoes and tomato products. In summary, there are a lot of investigations needed in the future to give reliable results to establish these CVD-preventive effects.     

A review of epidemiologic studies of tomatoes,lycopene, and prostate cancer

Prostate cancer is the most common cancer in American men. Preventable measures for this malignancy are not well established. Among potentially beneficial natural compounds is the carotenoid lycopene, which is derived largely from tomato-based products. Recent epidemiologic studies have suggested a potential benefit of this carotenoid against the risk of prostate cancer, particularly the more lethal forms of this cancer. Five studies support a 30% to 40% reduction in risk associated with high tomato or lycopene consumption, three are consistent with a 30% reduction in risk, but the results were not statistically significant, and seven were not supportive of an association. The largest relevant dietary study, a prospective study in male health professionals found that consumption of two to four servings of tomato sauce per week was associated with about a 35% risk reduction of total prostate cancer and a 50% reduction of advanced (extraprostatic) prostate cancer. Tomato sauce was by far the strongest predictor of plasma lycopene levels in this study. In the largest plasma-based study, very similar risk reductions were observed for total and advanced prostate cancer for the highest versus lowest quintile of lycopene. Other studies, mostly dietary case-control studies, have not been as supportive of this hypothesis. The reasons for these inconsistencies are unclear, but in three of the seven null studies, tomato consumption or serum lycopene level may have been too low to observe an effect. Because the concentration and bioavailability of lycopene vary greatly across the various food items, dietary questionnaires vary markedly in their usefulness of estimating the true variation in tissue lycopene concentrations across individuals. To optimize the interpretation of future findings, the usefulness of the questionnaire to measure lycopene levels in a population should be directly assessed. Although not definitive, the available data suggest that increased consumption of tomatoes and tomato-based products may be prudent.     

Lycopene,tomatoes, and the prevention of coronary heart disease

Coronary heart disease (CHD) is one of the primary causes of death in the Western world. The emphasis so far has been on the relationship between serum cholesterol levels and the risk of CHD. More recently, oxidative stress induced by reactive oxygen species (ROS) is also considered to play an important part in the etiology of this disease. Oxidation of the circulating low-density lipoprotein (LDL(ox)) is thought to play a key role in the pathogenesis of atherosclerosis and CHD. According to this hypothesis, macrophages inside the arterial wall take up the LDL(ox) and initiate the process of plaque formation. Dietary antioxidants such as vitamin E and beta-carotene have been shown in in vitro studies to prevent the formation of LDL(ox) and their uptake by microphages. In a recent study, healthy human subjects ingesting lycopene, a carotenoid antioxidant, in the form of tomato juice, tomato sauce, and oleoresin soft gel capsules for 1 week had significantly lower levels of LDL(ox) compared with controls. The antioxidant effects of lycopene have also been shown in four other human trials, including one where lycopene consumption reduced the levels of breath pentane. However, in one recent study, dietary supplementation with beta-carotene but not with lycopene was shown to inhibit LDL oxidation. The sources of lycopene used in most of these studies were either tomato products or lycopene extracted from tomatoes containing other carotenoids in various proportions. Therefore, it is not possible to attribute the effects solely to lycopene. Mechanisms other than the antioxidant properties of lycopene have also been shown to reduce the risk of CHD. Lycopene was shown to inhibit the activity of an essential enzyme involved in cholesterol synthesis in an in vitro and a small clinical study suggesting a hypocholesterolemic effect. Other possible mechanisms include enhanced LDL degradation, LDL particle size and composition, plaque rupture, and altered endothelial functions. Recent epidemiological studies have also shown an inverse relationship between tissue and serum levels of lycopene and mortality from CHD, cerebrovascular disease, and myocardial infraction. However, the most impressive population-based evidence comes from a multicenter case-control study where subjects from 10 European countries were evaluated for relationship between antioxidant status and acute myocardial infarctions. After adjusting for a range of dietary variables, only lycopene levels but not beta-carotene were found to be protective. At present, the role of lycopene in the prevention of CHD is strongly suggestive. Although the antioxidant property of lycopene may be one of the principal mechanism for its effect, other mechanisms may also be responsible. Controlled clinical and dietary intervention studies using well-defined subject populations and disease end points must be undertaken in the future to provide definitive evidence for the role of lycopene in the prevention of CHD. Mechanistic studies must also be initiated to understand the mode of lycopene action.     

Bioavailability of all-trans and cis-isomers of lycopene

Lycopene, the predominant carotenoid in tomatoes, is among the major carotenoids in serum and tissues of Americans. Although about 90% of the lycopene in dietary sources is found in the linear, all-trans conformation, human tissues contain mainly cis-isomers. Several research groups have suggested that cis-isomers of lycopene are better absorbed than the all-trans form because of the shorter length of the cis-isomer, the greater solubility of cis-isomers in mixed micelles, and/or as a result of the lower tendency of cis-isomers to aggregate. Work with ferrets, a species that absorbs carotenoids intact, has demonstrated that whereas a lycopene dose, stomach, and intestinal contents contained 6-18% cis-lycopene, the mesenteric lymph secretions contained 77%-cis isomers. The ferret studies support the hypotheses that cis-isomers are substantially more bioavailable then all-trans lycopene. In vitro studies suggest that cis-isomers are more soluble in bile acid micelles and may be preferentially incorporated into chylomicrons. The implications of these findings are not yet clear. Rats appear to accumulate lycopene in tissues within the ranges reported for humans, suggesting that they can be used to study effects of lycopene isomers on disease processes. Investigations are underway to determine whether there are biological differences between all-trans and various cis-isomers of lycopene regarding its antioxidant properties or other biological functions.     

Tomatoes,lycopene intake,and digestive tract and female hormone-related neoplasms

Tomato consumption showed a consistent inverse relation with the risk of digestive tract neoplasms in Italy in an integrated series of studies conducted in the 1980s. Another series of case-control studies was conducted between 1992 and 1999 in different areas of Italy. Cases were patients below age 80 with incident, histologically confirmed cancer of the oral cavity and pharynx (n = 754), esophagus (n = 304), colorectum (n = 1953), breast (n = 2529), and ovary (n = 1031). The comparison group involved, overall, over 5000 patients below age 80 with acute, non-neoplastic, nonhormone-related diseases, unrelated to long-term diet modifications and admitted to the same network of hospitals. Information was collected in hospital by trained interviewers using a validated food frequency questionnaire, including 78 foods or groups of foods, various alcoholic beverage, and fat-intake pattern. The multivariate relative risk (RR) of oral, pharyngeal, and esophageal cancer decreased across subsequent levels of lycopene intake to reach 0.7 (95% confidence interval [CI] 0.4-1.0) for oral and pharyngeal, and 0.7 (95% CI 0.4-1.1) for esophageal cancer in the highest quintile of intake. Both trends in risk were of borderline statistical significance. With reference to colorectal, breast, and ovarian cancer, although no consistent association was observed for lycopene (RR = 1.0 for colorectal, 1.2 for breast, and 1.1 for ovary in the highest quintile), tomato intake was inversely and significantly related with colorectal cancer (RR = 0.8). The inverse relation between lycopene and upper digestive tract neoplasms was not explained by alcohol or tobacco, sociodemographic factors, or total energy intake. The interpretation of such an inverse relation, however, remains open to discussion because it may be related to an effect of lycopene due to its antioxidant effect and/or a potential role of lycopene in decreasing insulin growth factor I, which is a promoter in the process of carcinogenesis.     

Overview of mechanisms of action of lycopene

Dietary intakes of tomatoes and tomato products containing lycopene have been shown to be associated with decreased risk of chronic diseases such as cancer and cardiovascular diseases in numerous studies. Serum and tissue lycopene levels have also been inversely related to the risk of lung and prostate cancers. Lycopene functions as a very potent antioxidant, and this is clearly a major important mechanism of lycopene action. In this regard, lycopene can trap singlet oxygen and reduce mutagenesis in the Ames test. However, evidence is accumulating for other mechanisms as well. Lycopene at physiological concentrations can inhibit human cancer cell growth by interfering with growth factor receptor signaling and cell cycle progression specifically in prostate cancer cells without evidence of toxic effects or apoptosis of cells. Studies using human and animal cells have identified a gene, connexin 43, whose expression is upregulated by lycopene and which allows direct intercellular gap junctional communication (GJC). GJC is deficient in many human tumors and its restoration or upregulation is associated with decreased proliferation. The combination of low concentrations of lycopene with 1,25-dihydroxyvitamin D3 exhibits a synergistic effect on cell proliferation and differentiation and an additive effect on cell cycle progression in the HL-60 promyelocytic leukemia cell line, suggesting some interaction at a nuclear or subcellular level. The combination of lycopene and lutein synergistically interact as antioxidants, and this may relate to specific positioning of different carotenoids in membranes. This review will focus on the growing body of evidence that carotenoids have unexpected biologic effects in experimental systems, some of which may contribute to their cancer preventive properties in models of carcinogenesis. Consideration of solubility in vitro, comparison with doses achieved in humans by dietary means, interactions with other phytochemicals, and other potential mechanisms such as stimulation of xenobiotic metabolism, inhibition of cholesterogenesis, modulation of cyclooxygenase pathways, and inhibition of inflammation will be considered. This review will point out areas for future research where more evidence is needed on the effects of lycopene on the etiology of chronic disease.     

Serum from rats fed red or yellow tomatoes induces Connexin43 expression independently from lycopene in a prostate cancer cell line

Epidemiologic studies suggested a protective effect of tomatoes against prostate cancer brought by lycopene, a carotenoid conferring the red colour of tomatoes. However, intervention studies on patients have shown that the preventive effect of tomato was more potent than that of lycopene. The aim of this study was to compare the effects of red tomato, yellow tomato (devoid of lycopene) and lycopene on Connexin43 (Cx43) expression, a protein regulating cell growth, on a prostate cancer cell line expressing the androgen receptor. Cells were incubated with serum from rats fed a control diet (CS) or control diet supplemented with red tomato (RTS), yellow tomato (YTS) or lycopene beadlets (LBS). After exposure of the cells to RTS or YTS for 48 h, the expression of Cx43 was significantly increased compared to cells exposed to CS. Whereas LBS effect was not significantly different. The cells incubated with RTS and LBS had similar levels of lycopene, while those incubated with YTS contained no lycopene. These data first show that serum nutritionally enriched with red and yellow tomatoes could up-regulate Cx43 turn-over in PC3AR cells independently from lycopene level. Within the physiological approach used in the present study, it can be concluded that compounds other than lycopene contribute to the preventive effect of tomatoes.     

Independent and interactive association of blood antioxidants and oxidative damage in elderly people

Oxidative stress is recognized as one of the major contributors to the increased risk of several diseases. Many recent population studies have established a close link between antioxidant defense and lowered risk of morbidity and mortality from cancer and heart disease, but little is known about the cooperative interactions of antioxidants. We examined the cross-sectional independent and interactive association of serum lipid-soluble antioxidant levels and free radical scavenging enzymes to serum malondialdehyde (MDA) levels, as a marker of oxidative damage. The participants were 160 nonsmoker institutionalized elderly. Upper tertile values of erythrocyte-superoxide-dismutase (E-SOD) constituted the strongest-associated single compound with a 74% decreased risk of high MDA. Upper tertiles of carotenoids and alpha-tocopherol independently showed a similar lowering of risk of about 57%. The highest tertiles of lycopene and either beta-carotene or alpha-tocopherol simultaneously reveal a higher decreased risk for oxidative damage (74 and 71%, respectively), very similar to those in the upper tertiles of all these three vitamins (75%). This study represents one of the few attempts to date to understand the interactive effect between antioxidants and suggests that lipid-soluble antioxidants act not individually, but rather cooperatively with each other. The efficacy of this interaction is more effective when lycopene is present.     

Statins and the Risk of Lung Cancer: A Meta-Analysis

Purpose

Several epidemiologic studies have evaluated the association between statins and lung cancer risk, whereas randomized controlled trials (RCTs) on cardiovascular outcomes provide relevant data as a secondary end point. We conducted a meta-analysis of all relevant studies to examine this association.

Methods

A systematic literature search up to March 2012 was performed in PubMed database. Study-specific risk estimates were pooled using a random-effects model.

Results

Nineteen studies (5 RCTs and 14 observational studies) involving 38,013 lung cancer cases contributed to the analysis. They were grouped on the basis of study design, and separate meta-analyses were conducted. There was no evidence of an association between statin use and risk of lung cancer either among RCTs (relative risk [RR] 0.91, 95% confidence interval [CI] 0.76–1.09), among cohort studies (RR 0.94, 95% CI 0.82–1.07), or among case-control studies (RR 0.82, 95% CI 0.57–1.16). Low evidence of publication bias was found. However, statistically significant heterogeneity was found among cohort studies and among case-control studies. After excluding the studies contributing most to the heterogeneity, summary estimates were essentially unchanged.

Conclusion

The results of our meta-analysis suggest that there is no association between statin use and the risk of lung cancer.     

A review of animal model studies of tomato carotenoids,lycopene, and cancer chemoprevention

There are relatively few reports on the cancer chemopreventive effects of lycopene or tomato carotenoids in animal models. The majority, but not all, of these studies indicate a protective effect. Inhibitory effects were reported in two studies using aberrant crypt foci, an intermediate lesion leading to colon cancer, as an end point and in two mammary tumor studies, one using the dimethylbenz(a)anthracene model, and the other the spontaneous mouse model. Inhibitory effects were also reported in mouse lung and rat hepatocarcinoma and bladder cancer models. However, a report from the author's laboratory found no effect in the N-nitrosomethylurea-induced mammary tumor model when crystalline lycopene or a lycopene-rich tomato carotenoid oleoresin was administered in the diet. Unfortunately, because of differences in routes of administration (gavage, intraperitoneal injection, intra-rectal instillation, drinking water, and diet supplementation), species and strain differences, form of lycopene (pure crystalline, beadlet, mixed carotenoid suspension), varying diets (grain-based, casein based) and dose ranges (0.5-500 ppm), no two studies are comparable. It is clear that the majority of ingested lycopene is excreted in the feces and that 1000-fold more lycopene is absorbed and stored in the liver than accumulates in other target organs. Nonetheless, physiologically significant (nanogram) levels of lycopene are assimilated by key organs such as breast, prostate, lung, and colon, and there is a rough dose-response relationship between lycopene intake and blood levels. Pure lycopene was absorbed less efficiently than the lycopene-rich tomato carotenoid oleoresin and blood levels of lycopene in rats fed a grain-based diet were consistently lower than those in rats fed lycopene in a casein-based diet. The latter suggests that the matrix in which lycopene is incorporated is an important determinant of lycopene uptake. A number of issues remain to be resolved before any definitive conclusions can be drawn concerning the anticancer effects of lycopene. These include the following: the optimal dose and form of lycopene, interactions among lycopene and other carotenoids and fat soluble vitamins such as vitamin E and D, the role of dietary fat in regulating lycopene uptake and disposition, organ and tissue specificity, and the problem of extrapolation from rodent models to human populations.     

Mechanistic understanding of β-cryptoxanthin and lycopene in cancer prevention in animal models

To better understand the potential function of carotenoids in the chemoprevention of cancers, mechanistic understanding of carotenoid action on genetic and epigenetic signaling pathways is critically needed for human studies. The use of appropriate animal models is the most justifiable approach to resolve mechanistic issues regarding protective effects of carotenoids at specific organs and tissue sites. While the initial impetus for studying the benefits of carotenoids in cancer prevention was their antioxidant capacity and pro-vitamin A activity, significant advances have been made in the understanding of the action of carotenoids with regards to other mechanisms. This review will focus on two common carotenoids, provitamin A carotenoid β-cryptoxanthin and non-provitamin A carotenoid lycopene, as promising chemopreventive agents or chemotherapeutic compounds against cancer development and progression. We reviewed animal studies demonstrating that β-cryptoxanthin and lycopene effectively prevent the development or progression of various cancers and the potential mechanisms involved. We highlight recent research that the biological functions of β-cryptoxanthin and lycopene are mediated, partially via their oxidative metabolites, through their effects on key molecular targeting events, such as NF-κB signaling pathway, RAR/PPARs signaling, SIRT1 signaling pathway, and p53 tumor suppressor pathways. The molecular targets by β-cryptoxanthin and lycopene, offer new opportunities to further our understanding of common and distinct mechanisms that involve carotenoids in cancer prevention.This article is part of a Special Issue entitled Carotenoids recent advances in cell and molecular biology edited by Johannes von Lintig and Loredana Quadro.     

Hypertension and Risk of Cataract: A Meta-Analysis

Background

Cataract is the major cause of blindness across the world. Many epidemiologic studies indicated that hypertension might play an important role in the development of cataract, while others not. We therefore conducted this meta-analysis to determine the relationship between risk of cataract and hypertension.

Methods

Retrieved studies on the association of hypertension with cataract risk were collected from PubMed, Web of Science and the Cochrane Library during June 2014 and were included into the final analysis according to the definite inclusion criteria. Odds ratio (OR) or risk ratio (RR) were pooled with 95% confidence interval (CI) to evaluate the relationship between hypertension and cataract risk. Subgroup analyses were carried out on the basis of cataract type, race and whether studies were adjusted for main components of metabolic syndrome (MS).

Results

The final meta-analysis included 25 studies (9 cohort, 5 case-control and 11 cross-sectional) from 23 articles. The pooled results showed that cataract risk in populations with hypertension significantly increased among cohort studies (RR 1.08; 95% CI: 1.05–1.12) and case-control or cross-sectional studies (OR 1.28; 95% CI: 1.12–1.45). This association was proved to be true among both Mongolians and Caucasians, and the significance was not altered by the adjustment of main components of MS. Subgroup analysis on cataract types indicated that an increased incidence of posterior subcapsular cataract (PSC) resulted among cohort studies (RR 1.22; 95% CI: 1.03–1.46) and cross-sectional/case-control studies (OR 1.23; 95% CI: 1.09–1.39). No association of hypertension with risk of nuclear cataract was found.

Conclusions

The present meta-analysis suggests that hypertension increases the risk of cataract, especially PSC. Further efforts should be made to explore the potential biological mechanisms.     

Oxidation of carotenoids by heat and tobacco smoke

The stability to autoxidation of the polar carotenoids, lutein and zeaxanthin, was compared to that of the less polar carotenoids, beta-carotene and lycopene at physiologically or pathophysiologically relevant concentrations of 2 and 6 microM, after exposure to heat or cigarette smoke. Three methodological approaches were used: 1) Carotenoids dissolved in solvents with different polarities were incubated at 37 and 80 degrees C for different times. 2) Human plasma samples were subjected to the same temperature conditions. 3) Methanolic carotenoid solutions and plasma were also exposed to whole tobacco smoke from 1-5 unfiltered cigarettes. The concentrations of individual carotenoids in different solvents were determined spectrophotometrically. Carotenoids from plasma were extracted and analyzed using high performance liquid chromatography. Carotenoids were generally more stable at 37 than at 80 degrees C. In methanol and dichloromethane the thermal degradation of beta-carotene and lycopene was faster than that of lutein and zeaxanthin. However, in tetrahydrofuran beta-carotene and zeaxanthin degraded faster than lycopene and lutein. Plasma carotenoid levels at 37 degrees C did not change, but decreased at 80 degrees C. The decrease of beta-carotene and lycopene levels was higher than those for lutein and zeaxanthin. Also in the tobacco smoke experiments the highest autoxidation rates were found for beta-carotene and lycopene at 2 microM, but at 6 microM lutein and zeaxanthin depleted to the same extent as beta-carotene. These data support our previous studies suggesting that oxidative stress degrade beta-carotene and lycopene faster than lutein and zeaxanthin. The only exception was the thermal degradation of carotenoids solubilized in tetrahydrofuran, which favors faster breakdown of beta-carotene and zeaxanthin.     

Pre-diagnostic circulating p53 autoantibodies and subsequent lung cancer risk in low-income African and European Americans

IntroductionMutations of the TP53 gene lead to the production of autoantibodies against p53, a major tumor suppressor protein. Although studies have indicated the association of p53 autoantibodies with human cancers, epidemiologic evidence on lung cancer is still lacking.MethodsIn this nested case-control study conducted within the Southern Community Cohort Study, we investigated the association of circulating p53 autoantibodies with the subsequent risk of developing lung cancer. Using blood samples collected prior to any cancer diagnosis from 295 cases and their individually matched controls, seroreactivity to p53 was assessed by fluorescent bead-based multiplex serology. Conditional logistic regression models were used to estimate odds ratios (OR) and 95 % confidence intervals (CI) for lung cancer risk associated with p53 autoantibodies.ResultsAfter adjustment for potential confounders, p53 seropositivity was significantly associated with an increased risk of lung cancer (OR=2.98, 95 % CI: 1.10–8.06) among African Americans, but not among European Americans (OR=1.21, 95 % CI: 0.24–6.15). The positive associations were restricted to men (OR=4.59, 95 % CI: 1.30–16.16) and participants with a short interval (≤ 4 years) from blood collection to diagnosis (OR=4.30, 95 % CI: 1.33–13.89).ConclusionOur findings add to the evidence supporting p53 autoantibodies as a biomarker of lung cancer.