Reduced Risk Of Prostate Cancer Research Articles

Tea consumption and prostate cancer: an updated meta-analysis

ObjectivesTea is supposed to have chemopreventive effect against various cancers. However, the protective role of tea in prostate cancer is still controversial. The aim of this study is to elucidate the association between tea consumption and prostate cancer risk by meta-analysis.MethodsA total of 21 published articles were retrieved via both computerized searches and review of references. Estimates of OR/RR for highest versus non/lowest tea consumption levels were pooled on the basis of random effect model or fixed effect model as appropriate. Stratified analyses on tea type, population and study design were also conducted.ResultsNo statistical significance was detected between tea consumption and prostate cancer risk in meta-analysis of all included studies (odds ratio (OR) = 0.86, 95% CI (0.69-1.04)). Furthermore, stratified analyses on population (Asian, OR = 0.81, 95% CI (0.55-1.08); non-Asian, OR = 0.89, 95% CI (0.72-1.07)) and tea type (green tea, OR = 0.79, 95% CI (0.43-1.14); black tea, OR = 0.88, 95% CI (0.73-1.02)) also yielded non-significant association. Only the case–control study subgroup demonstrated a borderline protective effect for tea consumption against prostate cancer (OR = 0.77, 95% CI (0.55-0.98)).ConclusionOur analyses did not support the conclusion that tea consumption could reduce prostate cancer risk. Further epidemiology studies are needed.

Two novel PRKCI polymorphisms and prostate cancer risk in an Eastern Chinese Han population

The atypical protein kinase C (aPKCι), encoded by the PRKCI gene, has been recently found to be a unique human oncoprotein, compared with some other diverse PKC isozymes. Genetic variations in PRKCI have also been reported to be associated with prostate cancer (PCa) risk in Caucasian populations, but no similar studies have been reported for Chinese populations. We genotyped two well-described PRKCI single nucleotide polymorphisms (SNPs) rs546950 and rs4955720 in 1015 PCa patients and 1044 cancer-free controls of Eastern Chinese men. SNPs in the vicinity of those two variants of PRKCI were evaluated using the in silico analysis. Logistic regression was then used to estimate their associations with and interactions in PCa risk. Although no significant main effects were found for the two tested SNPs in the single locus analysis, individuals carrying homozygote wide-type form of these two SNPs had slightly reduced PCa risk (adjusted OR = 0.63, 95% CI = 0.40-0.99, P = 0.045), compared with those carrying any of heterozygous or homozygous variant genotypes. Our results indicated that the two PRKCI SNPs were jointly associated with PCa risk in an Eastern Chinese population. Larger studies with multiethnic groups are warranted to confirm these findings and to explore the role of PRKCI SNPs in the etiology of PCa.

Re: Coffee consumption and risk of prostate cancer: an up-to-date meta-analysis

In their recent meta-analysis, Zhong et al.1 reported a 17% reduction in prostate cancer (PCa) risk when comparing highest versus non/lowest coffee consumption categories among 12 cohort studies1 (relative risk (RR)=0.83 (95% confidence interval (CI)=0.72–0.96)). Furthermore, they observed, from a dose-response meta-analysis, a 7% decreased risk of PCa for every two cups per day increase in coffee consumption (RR=0.93 (95% CI=0.88–0.99)). The authors also graphically presented that result in Figure 3b1. In the present letter, we would like to discuss two issues of that meta-analysis that we hope might draw attention to two fundamental steps of a meta-analysis: collection of the data and presentation of the results.

Inflammation in prostate biopsies may indicate reduced prostate cancer risk

Inflammation in prostate biopsies may indicate reduced prostate cancer risk

Is digoxin use for cardiovascular disease associated with risk of prostate cancer?

Digoxin is a commonly used medication for heart failure and cardiac arrhythmias that has recently been suggested as a novel chemotherapeutic agent. Preclinical studies of prostate cancer (PCa) have shown anti-tumor activity with digoxin. We explore the relationship between use of digoxin and PCa risk. Data from a population-based case-control study of incident cases aged 35-74 years at PCa diagnosis in 2002-2005 in King County, Washington were available. Controls were identified by random digit dialing and frequency matched by age. Use of digoxin was determined from in-person questionnaires regarding medical and prescription history. The relationship of digoxin use with PCa risk was evaluated with logistic regression. One thousand one cases of PCa and 942 controls were analyzed. The prevalence of digoxin use in controls was 2.7%, and use was positively correlated with age. In multivariate analysis adjusting for age, race, PSA screening, and family history of PCa, digoxin use was associated with a reduction in the odds ratio of PCa (OR 0.58, 95% CI: 0.30-1.10). Among those with ≥3 PSA tests over the preceding 5 years (546 cases, 380 controls), digoxin use was associated with a stronger reduction of PCa risk (OR 0.44, 95% CI: 0.20-0.98). These data indicate digoxin use may be associated with a reduction in risk of PCa. Given the potential mechanisms by which digoxin may exert an anti-neoplastic effect and other recent studies showing a negative association between digoxin use and PCa, further research is warranted.

Sarcosine and other metabolites along the choline oxidation pathway in relation to prostate cancer—A large nested case–control study within the JANUS cohort in Norway

Methyl group donors and intermediates of one-carbon metabolism affect DNA synthesis and DNA methylation, and may thereby affect prostate carcinogenesis. Choline, the precursor of betaine, and the one-carbon metabolite sarcosine have been associated with increased prostate cancer risk. Within JANUS, a prospective cohort in Norway (n = 317,000) with baseline serum samples, we conducted a nested case-control study among 3,000 prostate cancer cases and 3,000 controls. Using conditional logistic regression, odds ratios (ORs) and 95% confidence intervals (CIs) for prostate cancer risk were estimated according to quintiles of circulating betaine, dimethylglycine (DMG), sarcosine, glycine and serine. High sarcosine and glycine concentrations were associated with reduced prostate cancer risk of borderline significance (sarcosine: highest vs. lowest quintile OR = 0.86, CI = 0.72-1.01, p(trend) = 0.03; glycine: OR = 0.83, CI = 0.70-1.00, p(trend) = 0.07). Serum betaine, DMG and serine were not associated with prostate cancer risk. However, individuals with a high glycine/serine ratio were at decreased prostate cancer risk (OR = 0.74, CI = 0.69-0.85, p(trend) < 0.001). This population-based study suggested that men with high serum sarcosine or glycine concentrations have modestly reduced prostate cancer risk. Ratios of metabolites reflecting one-carbon balance may be associated with prostate cancer risk, as demonstrated for the glycine/serine ratio, and should be explored in future studies.

Reply to association between exercise and primary incidence of prostate cancer: Does race matter?

In our ultimate goal of determining whether exercise could have a potential role in reducing prostate cancer risk, we thank Dr. Kaufman for his letter to the editor concerning our article.1 However, there are several points that need clarification. First, we did not conclude that exercise had “a protective effect” for the cohort or the subgroups based on race, because our study merely examined associations between exercise and the risk of prostate cancer, and it was not designed to establish causality. Second, we acknowledged in our article that our report presents preliminary results in a small study sample from a single Veterans Affairs hospital and, thus, will require external validation involving larger cohorts from different settings. This would be a far better way to validate the relation between exercise and prostate cancer risk. This includes determining whether the disparity of the association by race holds true and establishing more generalizable estimates for the magnitude of these associations. Of note, the results from heterogeneity tests that were mentioned in the preceding letter can be unreliable when power is an issue.2 In addition, subgroup effects may well exist despite negative heterogeneity test results.3 Third, there is no evidence to support the idea that exercise has an impact on digital rectal examination (DRE) findings, as suggested by the commenter, and whether exercise has an impact on serum prostate-specific antigen (PSA) results is inconclusive.4 It is noteworthy that it seemed more clinically relevant to examine whether the relation between exercise and prostate cancer risk was independent of PSA results and DRE findings, especially for designing future studies. Indeed, if quantified exercise is proven to be an independent predictor of overall and/or high-grade prostate cancer, then it may aid in prebiopsy risk assessment and may even be included later in predictive nomograms designed for clinical use.5 We reported the relation between quantified exercise and prostate cancer risk as we have observed them among white and black veterans. We exercised caution to be certain that we would not overstate our conclusions, and we reiterate that future investigations are needed before any clinical recommendations may be formulated based on our findings. The preliminary nature of our report and the limitations inherent to such a study should not deter further investigations of exercise as a modifiable risk factor with a potential benefit against overall and/or aggressive prostate cancer and as a possible source of racial disparity that future discoveries could potentially mitigate. Lionel L. Bañez, MD1 Abhay A. Singh, MD2 1Veterans Affairs Medical Center, Durham, North Carolina 2Duke Prostate Center and Division of Urology, Duke University Medical Center, Durham, North Carolina

Sharing the responsibility of prostate cancer risk reduction

Despite improvements in the detection and management of prostate cancer in recent years, the clinical and financial burden of this disease continues to grow. Prostate cancer remains the most frequently diagnosed cancer in men and a leading cause of cancer death worldwide, yet there is still ongoing uncertainty surrounding the value of early screening. Intuitively, earlier detection should result in earlier and more effective treatment of prostate cancer; however, this has yet to be supported by the evidence, emphasized by the recent conflicting reports on screening from the Prostate, Lung, Colorectal and Ovarian (PLCO) and European trials. Still, as with any cancer, a diagnosis of prostate cancer carries a significant burden, and exploring the cost-benefit of risk reduction remains worthwhile. With primary care physicians assuming an increasingly greater role in the management of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms in general, urologists and primary care physicians are moving toward a more cooperative approach to the diagnosis and management of these conditions. This cooperation results in greater access to care and improved outcomes, as well as a reduced need for unnecessary surgical consultations. This supplement to the Canadian Urological Association Journal grew out of a series of meetings of the Prostate Cancer Collaborative Network (PCCN) – a multidisciplinary group of Canadian physicians dedicated to advancing the management of prostate cancer in Canada. Supported by an unrestricted educational grant from GlaxoSmithKline, the PCCN convened to explore new approaches to prostate cancer risk reduction. Along with their colleagues in the PCCN, Dr. Simon Tanguay discusses the shared roles of urology and primary care in the diagnosis and management of BPH, Dr. Yves Fradet provides a Canadian perspective on the burden of prostate disease, Dr. Larry Goldenberg reviews the role of 5-alpha reductase in prostate disease and Dr. Laurence Klotz addresses recent issues with Gleason grading. We hope this series of articles provides the reader with a comprehensive review of the current issues facing urologists, oncologists, radiation oncologists and primary care physicians involved in the management of prostate disease.

Marine-Derived Omega-3 Fatty Acids: Fishing for Clues for Cancer Prevention

Omega-3 fatty acids (FA) are polyunsaturated essential FA with anti-inflammatory properties. The most potent are the marine-derived eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which counteract the pro-inflammatory omega-6 FA. Americans take in an average of only 100 mg of EPA plus DHA per day resulting in a low omega-3:omega-6 intake ratio of 1:10 favoring inflammation. Cohort and/or case control studies suggest EPA and DHA are promising for breast, colon, and prostate cancer risk reduction. Mechanistic studies largely in preclinical models suggest EPA and DHA reduce synthesis of prostaglandin E2 and other inflammatory cytokines, decrease aromatase activity and proliferation, promote differentiation and apoptosis, and enhance insulin sensitivity. Animal models using 7% to 20% omega-3 added to chow are promising; however, this amount of omega-3 in a diet is unlikely to be acceptable to humans. The optimal EPA:DHA ratio or the lowest effective dose of EPA and DHA for cancer prevention is unclear, but it is likely to be more than 600 mg/day, which is six times the average American intake. Most phase II prevention trials use 1 to 3.3 g of EPA and DHA, which is safe and well tolerated. Two grams of EPA was associated with fewer polyps in individuals with familial adenomatous polyposis in a randomized, placebo-controlled trial. Identification of serum risk biomarkers modulated by EPA and DHA in healthy humans has remained elusive, but phase II prevention trials with tissue obtained for risk and response biomarkers are ongoing.

Pharmaco-prévention et nutri-prévention des cancers de la prostate

In 2010, in France, 8,790 men died from prostate cancer despite a low and decreasing mortality rate. The individual risk/benefit ratio of prostate cancer screening is the focus of controversy and currently not in favor of a systematic screening program. Therefore, only prevention could reduce incidence, side effects of treatment and related mortality. Interestingly, prostate cancer prevention is also a field of controversy mainly about 5-alpha-reductase inhibitors. However, it could be expected that pharmaco- or diet-based prevention will be a huge tool for cancer control, even more for prostate cancer burden. This review comprehensively analyses which molecules or compounds could be used in preventive trials. With regard to pharmaco-prevention, three different kinds of drugs could be identified. First drugs, which aim at mainly or even solely reduce prostate cancer risk such as 5-alpha-reductase inhibitors and selective estrogen receptor modulators. Drugs, which aim at wider preventive impact such as: nonsteroidal anti-inflammatory drugs or difluoromethylornithine. Lastly, drugs for which reducing prostate cancer incidence is merely a side effect such as statins, metformin or histones desacetylase inhibitors. With regard to diet-based prevention, two main approaches could be identified: aliments and nutriments, on one hand, and vitamin and minerals, on the other. Interestingly if compounds reach experimental plausibility, natural foods or even global diet seem to have a higher impact. Lastly, besides assessment of efficacy, effectiveness required the critical step of compliance, which might actually be the weakest link of the prevention chain.

Exercise Does Not Counteract the Effects of a “Westernized” Diet on Prostate Cancer Xenografts

The relationships between diet, exercise, and prostate cancer (PCa) remain unclear. We have previously reported that a "Western" diet promotes PCa tumor growth in vivo. Presently, we report the effects of sustained aerobic exercise on PCa progression in animals fed a high-fat diet versus a standard diet. Athymic mice (n = 43) were inoculated subcutaneously with human PCa (LNCaP) cells, fed ad libitum with either a high-fat or a standard diet, and randomized into forced exercising and non-exercising groups. Body weight, tumor volume, and food consumption were recorded tri-weekly. Terminal serum samples and tumor biopsies were obtained for analysis. Body weight differences were not observed between the groups over time. The high-fat diet with exercise (HF-Ex) group showed significantly increased tumor growth rate compared to all other groups (P < 0.0007). Tumor growth rate of the standard diet with exercise (Std-Ex) group was reduced significantly compared to the high-fat diet without exercise (HF-No Ex) group (P = 0.0008). Significant differences (P ≤ 0.012) were observed in energy consumption (kcal) between the groups over time. Exercising mice consumed significantly more kcal than non-exercising mice, and the HF-Ex group consumed significantly more than each of the other three groups (P < 0.0007). The expression levels of p27 and p21 were increased in exercising animals, while AR expression was elevated in the HF-Ex group versus the Std-Ex and HF-No Ex groups. Sustained aerobic exercise did not counteract the tumor-promotional effect of increased consumption of a high-fat diet, suggesting that diet is more influential in PCa progression than exercise. Combining exercise with a healthy diet reduced the rate of PCa progression in this model. This study may have implications for PCa risk reduction in humans.

Weighing the data on diet and prostate cancer

In 2001, my colleagues and I asked whether the link between nutrition and prostate cancer was evidence-based or merely a suspicion.1 The descriptive epidemiology of prostate cancer suggests that it is indeed a preventable disease. The evidence and scientific data of a variety of prevention strategies include, among many others, dietary fat reduction.2 Omega-3 and omega-6 polyunsaturated fatty acids are essential fatty acids. The Western diet contains a disproportionally high amount of omega-6 and a low amount of omega-3 polyunsaturated fatty acids, and the resulting high omega-6/omega-3 ratio is thought to contribute to cardiovascular disease, inflammation and cancer. Studies in human populations have linked high consumption of fish or fish oil to a reduced risk of colon, prostate and breast cancer, although other studies have failed to find a significant association. Nonetheless, the available epidemiological evidence, combined with the demonstrated effects of omega-3 polyunsaturated fatty acids on cancer in animal and cell culture models, has motivated the development of clinical interventions using omega-3 polyunsaturated fatty acids in the prevention of cancer.3 In this issue of CUAJ, Amin and colleagues4 have addressed an interesting issue, namely, the impact of nutritional factors on prostate cancer development. They looked at a database of 917 patients planned to have transrectal ultrasonography–guided biopsies based on an elevated serum prostate-specific antigen (PSA) level, a rising serum PSA level or an abnormal digital rectal examination. They also performed univariable and multivariable logistic regression analysis for prediction of cancer and its aggressiveness using a self-administered food frequency questionnaire given before the biopsies. The authors found that on multivariable analyses, a meat diet including red meat, ham and sausages was associated with an increased risk of prostate cancer, and a fish diet was associated with less prostate cancer. None of the tested dietary components were associated with prostate cancer aggressiveness. The authors have nicely pointed out the strengths and weaknesses of their study, including its limitations. By definition, case–control studies are prone to certain types of unavoidable biases. However, the strength of the paper lies in its multivariable analysis and the detailed questionnaire that patients completed before undergoing the prostate biopsy. Noteworthy, red meat, ham and sausages as well as fish clearly had unfavourable and favourable impacts, respectively. Potatoes, interestingly enough, had a protective odds ratio close to statistical significance although it is not clear whether this has something to do with potatoes themselves or whether patients who eat a lot of potatoes actually have other types of dietary habits that protect them. With respect to the incidence of aggressive prostate cancer and its relation to diet, it is not clear whether the absence of an association was due to the low number of cancers found in that group or whether increasing the number of these patients would have potentially brought positive results. For instance, with respect to pulses, such as beans and peas, the odds ratio for a Gleason score above 7 and number of cancer cores above 3 was, respectively, 1.86 and 2.89. Most odds ratios close to 3 would probably be significant on a large patient population. Recently, the association between prostate cancer risk and fresh and preserved fish consumption among participants of a population-based case–control study (1534 cases, 1607 controls) was investigated in Canada.5 Fish intake was measured using a dietary questionnaire that collected frequency of consumption of a given portion size of both fresh and preserved fish. Logistic regression analysis demonstrated an inverse association between preserved fish and prostate cancer risk for all levels of consumption, but reductions only reached statistical significance for the category of 1 to 3 servings of preserved fish per month (odds ratio 0.78, confidence interval 0.64–0.95). Consumption of any fat or energy from preserved fish was also associated with reduced risk. There was no suggestion of reduced prostate cancer risk with consumption of fresh and canned fish. These results suggest that consumption of preserved fish may reduce the risk of developing prostate cancer. It is not crystal clear why the difference between preserved and fresh fish is so important, but it warrants further study. These sometimes contradictory results highlight our limitations in the understanding and effectiveness of prostate cancer preventive means and the numerous grey areas that need additional investigations.

Abstract LB-15: Frequency of aspirin use and prostate cancer mortality among prostate cancer cases in the control arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.

Abstract Background: Aspirin may slow progression of cancer through the inhibition of platelet aggregation as experimental research has shown that platelets play a role in cancer cell dissemination and metastatic growth. While a 10% reduction in prostate cancer risk has been associated with regular aspirin use, only a few epidemiological studies have evaluated the association between aspirin use and prostate cancer mortality among prostate cancer cases. Methods: Participants included 3857 men, age 55-74, who were diagnosed with prostate cancer in the control arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial between 1993-2009. The frequency of aspirin use one year prior to baseline (1993-2001) was ascertained through a self-administered questionnaire. Death due to prostate cancer was ascertained by annual questionnaire and linkage to the National Death Index. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using COX proportional hazards models using age as the time metric and adjusting for clinical stage, Gleason score, primary treatment, smoking status, body mass index, race, history of heart attack, and history of stroke. Results: After a median of 5 years of follow-up, 136 cases died of prostate cancer. No significant association with prostate cancer mortality was observed between cases who reported pre-diagnostic daily or more than daily aspirin use compared to cases who reported no aspirin use (HR=0.77; 95% CI 0.48-1.25). Among those diagnosed with clinically advanced stage (III, IV) disease, an inverse association with prostate cancer mortality was observed for cases who reported daily or more than daily aspirin use (HR=0.37; 95% CI 0.15-0.92), while no association for daily or more than daily users was seen among those with clinically localized prostate cancer (HR=0.86; 95% CI 0.47-1.58). Conclusion: Pre-diagnostic use of aspirin was not significantly associated with prostate cancer mortality based on cases diagnosed in the PLCO control arm, although a reduction in risk of prostate cancer mortality was observed among those with advanced stage disease in a subgroup analysis. Citation Format: Sarah E. Daugherty, Ruth Pfeiffer, Armen Ghazarian, Grant Izmirlian, Phil Prorok, Katherine McGlynn. Frequency of aspirin use and prostate cancer mortality among prostate cancer cases in the control arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-15. doi:10.1158/1538-7445.AM2013-LB-15

Abstract 3620: Diabetes mellitus and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition.

Abstract The current epidemiologic evidence suggests that men with type 2 diabetes mellitus may be at lower risk of developing prostate cancer. More research is needed to clarify whether and how time since diabetes diagnosis, diabetes treatment, stage and grade of prostate cancer, age at recruitment, adiposity, and physical activity modify the risk profile. We assessed the association of self-reported history of diabetes mellitus diagnosis at baseline with risk of prostate cancer among 139,131 men recruited into the European Prospective Investigation into Cancer and Nutrition (EPIC), after excluding men with prevalent cancer at recruitment and men who did not return the baseline questionnaires or had missing information about their history of diabetes. After an average of 12 years follow-up, 4,531 prostate cancers were diagnosed, of which 894 men had advanced (T3-4, N+, M+) disease and 1,688 had localized disease (T0-2, N0, M0); 375 men had high-grade disease (Gleason score ≥ 8) disease and 1,811 had low-grade disease (Gleason score &amp;lt; 8). Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards models stratified by EPIC recruitment center and age at enrolment, and adjusted for body mass index, waist circumference, cigarette smoking status, university education, physical activity, and daily dietary intake of energy, alcohol, fruits and vegetables, fish, calcium and protein from dairy sources. A total of 5,100 men (3.7%) stated at baseline that they had a history of diabetes mellitus. Men with diabetes had a 26% reduced risk of developing prostate cancer compared to men without diabetes (HR, 0.74; 95% CI, 0.63-0.86). There was no significant reduction in risk in the first two years after diabetes diagnosis (No. of cases, 39; HR, 0.83; 95% CI, 0.60-1.14), but was evident for men diagnosed between 3 to 6 years after diagnosis (No. of cases, 32; HR, 0.72; 95% CI, 0.51-1.02) and 7-12 years (No. of cases, 32; HR, 0.75; 95% CI, 0.53-1.07), and was even lower for men who had been diagnosed for more than 12 years (No. of cases, 31; HR, 0.64; 95% CI, 0.45-0.92). Compared to non-diabetics, diabetic men not receiving insulin treatment at baseline had a risk of prostate cancer (HR, 0.75; 95% CI, 0.60-0.94) similar to what of diabetic men who were receiving insulin (HR, 0.78; 95% CI, 0.59-1.03). These results did not differ by stage and grade of prostate cancer, or by age at recruitment, adiposity, or physical activity. Our results are compatible with the hypothesis that diabetes is associated with reduced prostate cancer risk. A potential biological explanation underlying this association is that men with severe type 2 diabetes may manifest lower testosterone concentrations, which provide an environment that is not conducive to proliferation of prostate cancer cells. Citation Format: Konstantinos K. Tsilidis, Naomi Allen, Ruth Travis, Sabine Rohrmann, Ute Nöthlings, Larraitz Arriola, Marc Gunter, Timothy Key. Diabetes mellitus and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3620. doi:10.1158/1538-7445.AM2013-3620

218 INTERACTIONS BETWEEN DIET AND THE C161T POLYMORPHISMS IN THE PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-GAMMA (PPAR-γ) GENE IN PROSTATE CANCER RISK IN JAPANESE MEN

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History (I)1 Apr 2013218 INTERACTIONS BETWEEN DIET AND THE C161T POLYMORPHISMS IN THE PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-GAMMA (PPAR-γ) GENE IN PROSTATE CANCER RISK IN JAPANESE MEN Ryosuke Ando, Teruo Nagaya, Sadao Suzuki, Toshiki Etani, Taku Naiki, Noriyasu Kawai, Keiichi Tozawa, Shinkan Tokudome, and Kenjiro Kohri Ryosuke AndoRyosuke Ando Nagoya, Japan More articles by this author , Teruo NagayaTeruo Nagaya Nagoya, Japan More articles by this author , Sadao SuzukiSadao Suzuki Nagoya, Japan More articles by this author , Toshiki EtaniToshiki Etani Nagoya, Japan More articles by this author , Taku NaikiTaku Naiki Nagoya, Japan More articles by this author , Noriyasu KawaiNoriyasu Kawai Nagoya, Japan More articles by this author , Keiichi TozawaKeiichi Tozawa Nagoya, Japan More articles by this author , Shinkan TokudomeShinkan Tokudome Tokyo, Japan More articles by this author , and Kenjiro KohriKenjiro Kohri Nagoya, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1598AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The C161T polymorphism in the peroxisome proliferator-activated receptor gamma (PPAR-γ) gene has been associated with a reduced risk for coronary artery disease and colorectal adenomas. However, the relationship between C161T polymorphism and cancer risk appears limited and controversial. We examined the associations of diet, PPAR-γ polymorphisms (C161T), and gene-diet interactions with prostate cancer risk in Japanese men. METHODS Samples were obtained from 110 newly diagnosed prostate cancer cases and 214 biopsy-negative controls. Daily consumption of energy and macronutrients was compared between cases and controls. We used logistic regression analysis to estimate the odds ratio (OR) and 95% confidence interval (CI) for prostate cancer risk according to the genotype of the C161T polymorphism. Interactions between low/high nutrient intakes and the PPAR-γ gene polymorphism in prostate cancer risk were proved. RESULTS The daily intake of energy and macronutrients was not different between cases and controls. The C161T substitution was associated with reduced prostate cancer risk. T allele carriers of C161T showed a protective effect (multiple-adjusted OR, 0.53; 95% CI, 0.31-0.93) against prostate cancer. Among the low fat and carbohydrate intake groups, T allele carriers of C161T had reduced prostate cancer risk (multiple-adjusted OR [95% CI], 0.33 [0.13-0.83] and 0.42 [0.18-0.97], respectively); however, there were no interactions between the consumption of nutrients and PPAR-α gene polymorphisms in prostate cancer risk. CONCLUSIONS Prostate cancer can arise from interactions between high fat consumption and gene polymorphisms influencing lipid metabolism, such as in the PPAR-γ gene. PPAR-γ gene C161T substitution was associated with decreased prostate cancer risk in Japanese men. Low intake of fat or carbohydrate may strengthen the risk reduction by C161T substitution. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e89-e90 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ryosuke Ando Nagoya, Japan More articles by this author Teruo Nagaya Nagoya, Japan More articles by this author Sadao Suzuki Nagoya, Japan More articles by this author Toshiki Etani Nagoya, Japan More articles by this author Taku Naiki Nagoya, Japan More articles by this author Noriyasu Kawai Nagoya, Japan More articles by this author Keiichi Tozawa Nagoya, Japan More articles by this author Shinkan Tokudome Tokyo, Japan More articles by this author Kenjiro Kohri Nagoya, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Associations of tea and coffee consumption with prostate cancer risk

Tea and coffee contain bioactive compounds and both beverages have recently been associated with a reduced risk of prostate cancer (PCa). We studied associations of tea and coffee consumption with PCa risk in a population-based case-control study from King County, Washington, USA. Prostate cancer cases were diagnosed in 2002-2005 and matched to controls by 5-year age groups. Logistic regression was used to generate odds ratios (ORs) and 95 % confidence intervals (CIs). Among controls, 19 and 58 % consumed at least one cup per day of tea and coffee, respectively. The analysis of tea included 892 cases and 863 controls, and tea consumption was associated with a reduced overall PCa risk with an adjusted OR of 0.63 (95 % CI: 0.45, 0.90; P for trend = 0.02) for men in the highest compared to lowest category of tea intake (≥2 cups/day vs. ≤1 cup/week). Risk estimates did not vary substantially by Gleason grade or disease stage. Coffee consumption was not associated with risk of overall PCa or PCa in subgroups defined by tumor grade or stage. Our results contribute further evidence that tea consumption may be a modifiable exposure that reduces PCa risk.

Association between exercise and primary incidence of prostate cancer

Exercise is a modifiable lifestyle risk factor associated with prostate cancer risk reduction. However, whether this association is different as a function of race is unclear. In the current study, the authors attempted to characterize the link between exercise and prostate cancer (CaP) in white and black American men. Using a prospective design, 307 men (164 of whom were white and 143 of whom were black) who were undergoing prostate biopsy completed a self-reported survey that assessed exercise behavior (metabolic equivalent [MET] hours per week). Crude and adjusted logistic regression analyses were used to estimate the risk of prostate cancer controlling for age, body mass index, digital rectal examination findings, previous biopsy, Charlson comorbidity score, and family history of CaP stratified by self-reported race. There was no significant difference noted with regard to the amount of exercise between racial groups (P = .12). Higher amounts of MET hours per week were associated with a decreased risk of CaP for white men in both crude (P = .02) and adjusted (P = .04) regression models. Among whites, men who exercised ≥ 9 MET hours per week were less likely to have a positive biopsy result compared with men exercising < 9 MET hours per week (odds ratio, 0.47; 95% confidence interval, 0.22-0.99 [P = .047]). There was no association noted between MET hours per week and risk of CaP among black men in both crude (P = .79) and adjusted (P = .76) regression models. In a prospective cohort of men undergoing biopsy, increased exercise, measured as MET hours per week, was found to be associated with CaP risk reduction among white but not black men. Investigating race-specific mechanisms by which exercise modifies CaP risk and why these mechanisms disfavor black men in particular are warranted.

Serum folate and vitamin B12 concentrations in relation to prostate cancer risk--a Norwegian population-based nested case-control study of 3000 cases and 3000 controls within the JANUS cohort

Although individual studies have been inconsistent, meta-analyses of epidemiological data suggest that high folate and vitamin B12 levels may be associated with increased prostate cancer risk. Within JANUS, a prospective cohort in Norway (n = 317 000) with baseline serum samples, we conducted a nested case-control study among 3000 prostate cancer cases and 3000 controls, matched on age and time at serum sampling, and county of residence. Using conditional logistic regression, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer risk were estimated according to quintiles of serum folate, vitamin B12, methylmalonic acid (MMA), total homocysteine (tHcy) and methionine, and according to MTHFR 677C→T genotypes. To correct for degradation during sample storage, folate concentration was measured as p-aminobenzoylglutamate (pABG) equivalents following oxidation and acid hydrolysis. We observed a weak positive association between folate concentration and prostate cancer risk [OR highest vs lowest quintile = 1.15 (0.97-1.37), P-trend = 0.04], which was more pronounced among individuals ≥ 50 years at inclusion [OR 1.40 (1.07-1.84), P-trend = 0.02]. tHcy showed an inverse trend with risk [OR 0.92 (0.77-1.10), P-trend = 0.03]. Vitamin B12, MMA and methionine concentrations were not associated with prostate cancer risk. Compared with the MTHFR 677CC genotype, the CT and TT variants, both of which were related to lower folate concentrations, were associated with reduced prostate cancer risk [OR 0.82 (0.72-0.94) and OR 0.78 (0.64-0.94), respectively]. This large-scale population-based study suggests that high serum folate concentration may be associated with modestly increased prostate cancer risk. We did not observe an association between vitamin B12 status and prostate cancer risk.

Diabetes Mellitus Reduces Prostate Cancer Risk - No Function of Age at Diagnosis or Duration of Disease

Prior studies examining the relation between diabetes mellitus (DM) and prostate cancer risk have reported controversial findings. We examined this association by conducting a detailed meta-analysis of the peer-reviewed literature. A comprehensive search for articles of MEDLINE and EMBASE databases and bibliographies of retrieved articles published up to November, 2012 was performed. Methodological quality assessment of the trials was based on the Newcastle-Ottawa Scaleq and the meta-analysis was performed using STATA 12.0. Dose-response regression was conducted with SPSS 19.0. We included 29 studies in the meta-analysis (13 case-control studies, 16 cohort studies), and found an inverse association between DM and prostate cancer (relative risk (RR) 0.84, 95% confidence interval (CI), 0.78-0.91). An inverse association was also observed in non-Asian populations (RR 0.81, 95% CI 0.76-0.87) and population-based studies (RR 0.80, 95% CI 0.77-0.91). No statistical significance was found of the association between prostate cancer risk and the duration of DM (p=0.338), and risk seemed not related with the age of DM diagnosis. This study suggested an inverse relationship between DM and prostate cancer, but without links to duration of disease or age of diagnosis.

Highlights of This Issue

Although alcohol consumption is an established risk factor for incident breast cancer, its role in breast cancer prognosis is unclear. Kwan and colleagues evaluated postdiagnosis alcohol consumption with both cancer recurrence and mortality among 9,329 breast cancer patients in the After Breast Cancer Pooling Project. The authors report that regular alcohol intake was not associated with risk of breast cancer recurrence; however, postmenopausal women who regularly consumed alcohol had increased risk of recurrence.There is a positive association between calcium intake and prostate cancer risk. Rowland and colleagues evaluated whether this association was modified by particular vitamin D receptor (VDR) genotypes that influence calcium absorption. Among men with a low calcium absorption VDR genotype, those in the lowest quartile of calcium intake had a 50% reduction in prostate cancer risk compared with those in the upper quartiles of calcium intake. These findings are consistent with the hypothesis that genetic determinants of calcium absorption influence prostate cancer risk and may contribute to racial disparities in prostate cancer incidence and mortality rates.The interpretation of uterine cancer rates is complicated because risk estimates often include women who have already undergone hysterectomies. To address this, Siegel and colleagues used population-based cancer registries, U.S. Census data and data from the Behavioral Risk Factor Surveillance System to estimate hysterectomy-corrected, age-adjusted uterine cancer rates. The authors report that stateby-state hysterectomy-corrected uterine cancer incidence rates were consistently higher than uncorrected rates. Failure to adjust uterine cancer rates for hysterectomy prevalence distorts the true geographic and racial patterns.There is strong association between high viral load (VL) of human papillomavirus (HPV) type 16 and risk for cervical cancer in situ (CIS), yet little data is available regarding HPV16 and invasive SCC. Sundström and colleagues evaluated HPV16 VL in women with CIS and invasive SCC and found low VLs were common among both CIS and SCC cases. In SCC cases, high HRV16 VL conferred increased risk, but only from 3 years before diagnosis, which differs considerably from CIS cases. HPV16 VL dynamics are complex in SCC, which may limit its use in screening.