Risk Of Advanced Prostate Cancer Research Articles

Association of selenium, tocopherols, carotenoids, retinol, and 15-isoprostane F2t in serum or urine with prostate cancer risk: the multiethnic cohort

We examine the association of antioxidants and 15-isoprostane F(2t) with risk of prostate cancer. We conducted a nested case-control study of serum antioxidant biomarkers (selenium, tocopherols, carotenoids, and retinol) and a urinary oxidation biomarker (15-isoprostane F(2t)) with risk of prostate cancer within the Multiethnic Cohort. Demographic, dietary, and other exposure information was collected by self-administered questionnaire in 1993-1996. We compared prediagnostic biomarker levels from 467 prostate cancer cases and 936 cancer free controls that were matched on several variables. Multivariate conditional logistic regression models were used to compute adjusted odds ratios (ORs) and 95% confidence intervals (CIs). We observed that there was no overall association of serum concentrations of antioxidants and urinary concentrations of 15-isoprostane F(2t) with risk of prostate cancer or risk of advanced prostate cancer. However, we did observe an inverse association for serum selenium only among African-American men (p trend = 0.02); men in the third tertile of selenium concentrations had a 41% lower risk (95% CI: 0.38-0.93) of prostate cancer when compared to men in the first tertile. Overall, our study found no association of serum antioxidants or 15-isoprostane F(2t) with the risk of prostate cancer. The observed inverse association of selenium with prostate cancer in African-Americans needs to be validated in other studies.

Plasma Isoflavones and Subsequent Risk of Prostate Cancer in a Nested Case-Control Study: The Japan Public Health Center

The incidence of prostate cancer is much lower in Japanese than Western populations. Given the preventive effects of isoflavones on carcinogenesis in the prostate in many nonhuman studies and the high consumption of isoflavones in Japanese, this low incidence may be partly due to the effects of soy. We conducted a nested case-control study within the Japan Public Health Center-based Prospective Study. A total of 14,203 men aged 40 to 69 years who had returned the baseline questionnaire and provided blood samples were observed from 1990 to 2005. During a mean of 12.8 years of follow-up, 201 newly diagnosed prostate cancers were identified. Two matched controls for each case were selected from the cohort. Conditional logistic regression model was used to estimate the odds ratios (ORs) and 95% CIs for prostate cancer in relation to plasma levels of isoflavone. Plasma genistein level tended to be inversely associated with the risk of total prostate cancer. Although plasma daidzein showed no association, the highest tertile for plasma equol, a metabolite of daidzein, was significantly associated with a decreased risk of total prostate cancer (OR = 0.60; 95% CI, 0.36 to 0.99; P(trend) = .04). These inverse associations were strengthened after analysis was confined to localized cases, with ORs in the highest group of plasma genistein and equol compared with the lowest of 0.54 (95% CI, 0.29 to 1.01; P(trend) = .03) and 0.43 (95% CI, 0.22 to 0.82; P(trend) = .02), respectively. Plasma isoflavone levels were not statistically significantly associated with the risk of advanced prostate cancer. Isoflavones may prevent the development of prostate cancer.

The Influence of Statin Medications on Prostate-specific Antigen Levels

Recent data suggest that statin use may be associated with a reduced risk of advanced prostate cancer. However, the influence of statins on prostate-specific antigen (PSA) levels and what effect this could potentially have on prostate cancer diagnosis are unknown. We conducted a longitudinal study of 1214 men who were prescribed a statin between 1990 and 2006 at the Durham Veterans Affairs Medical Center who were free of prostate cancer, had not undergone prostate surgery or taken medications known to alter androgen levels and who had at least one PSA value within 2 years before and at least one PSA value within 1 year after starting a statin. The change in PSA from before to after statin treatment was analyzed as a continuous variable using the Wilcoxon signed rank test. The association between change in PSA and change in cholesterol parameters (low-density lipoprotein [LDL], high-density lipoprotein [HDL], and total cholesterol) was analyzed using multivariate linear regression. All statistical tests were two-sided. Mean (SD) age when starting statins was 60.3 (8.3) years; median prestatin PSA concentration was 0.9 (1.9) ng/mL; and mean prestatin LDL cholesterol concentration was 144 (34) mg/dL. After starting a statin, the median LDL decline was 27.5%, and the median PSA decline was 4.1% (P < .001, for both comparisons). Changes in PSA concentration were strongly associated with statin dose and changes in LDL levels. For every 10% decrease in LDL after starting a statin, PSA levels declined by 1.64 (95 % confidence interval [CI] = 0.64% to 2.65%, p = .001). Among men most likely to be under consideration for prostate biopsy (prestatin PSA levels > or =2.5 ng/mL, n = 188), those with >41% declines in LDL (highest quartile) after starting a statin experienced a 17.4% (95% CI = 10.0% to 24.9%) decline in serum PSA. PSA levels declined by a statistically significant extent after initiation of statin treatment. The reduction was most pronounced among men with the largest LDL declines and those with PSA levels that would make them candidates for prostate biopsy. By lowering PSA levels, statins may complicate cancer detection, although further studies are needed to quantify the clinical significance of this effect.

Body Size and Risk of Prostate Cancer in the European Prospective Investigation into Cancer and Nutrition

Body size has been hypothesized to influence the risk of prostate cancer; however, most epidemiologic studies have relied on body mass index (BMI) to assess adiposity, whereas only a few studies have examined whether body fat distribution predicts prostate cancer. We examined the association of height, BMI, waist and hip circumference, and waist-hip ratio with prostate cancer risk among 129,502 men without cancer at baseline from 8 countries of the European Prospective Investigation into Cancer and Nutrition (EPIC), using Cox regression, with age as time metric, stratifying by study center and age at recruitment, and adjusting for education, smoking status, alcohol consumption, and physical activity. During a mean follow-up of 8.5 years, 2,446 men developed prostate cancer. Waist circumference and waist-hip ratio were positively associated with risk of advanced disease. The relative risk of advanced prostate cancer was 1.06 (95% confidence interval, 1.01-1.1) per 5-cm-higher waist circumference and 1.21 (95% confidence interval, 1.04-1.39) per 0.1-unit-higher waist-hip ratio. When stratified by BMI, waist circumference and waist-hip ratio were positively related to risk of total, advanced, and high-grade prostate cancer among men with lower but not among those with higher BMI (Pinteraction for waist with BMI, 0.25, 0.02, and 0.05, respectively; Pinteraction for waist-hip ratio with BMI, 0.27, 0.22, and 0.14; respectively). These data suggest that abdominal adiposity may be associated with an increased risk of advanced prostate cancer. This association may be stronger among individuals with lower BMI; however, this finding needs confirmation in future studies.

Abstract B131: A prospective study of phytanic acid intake from red meat and dairy products and prostate cancer risk

Abstract B131 Phytanic acid - a 3-methyl branched-chain fatty acid - is found almost exclusively in red meat and dairy products, and may contribute to the increases in prostate cancer risk that are consistently observed with higher intakes of these animal foods. The potential importance of phytanic acid in prostate carcinogenesis is further underscored by evidence that the branched-chain fatty acid oxidation pathway is selectively upregulated in prostate tumors. We constructed a novel summary measure of phytanic acid intake and prospectively examined its association with prostate cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. At baseline, 27,111 Finnish male smokers 50 to 69 years old provided information on demographic, smoking, medical, and other risk factors, and completed a 276-item diet history questionnaire that ascertained frequency of consumption and portion size. Since phytanic acid is not currently included in food composition tables, we used the published phytanic acid content of 151 major food items, including butter, cheese, cream, ice cream, milk, yogurt, and beef products, to estimate total daily intake. Between 1985 and 2006, a total of 1,929 incident prostate cancer cases, including 438 cases of advanced disease (defined as TNM stage 3 or 4 and / or Gleason grade of 8 or higher), were identified. In Cox proportional hazards models adjusted for age, smoking dose and duration, body mass index, education, family history of prostate cancer, energy intake, and trial intervention assignment, higher estimated phytanic acid intake was associated with increased risks of advanced prostate cancer in a non-linear manner. The relative risks and 95% confidence intervals for advanced prostate cancer according to increasing quartiles of phytanic acid intake were 1.00 (referent), 1.29 (0.90-1.86), 1.56 (1.11-2.21), and 1.34 (0.94-1.92); p trend = 0.23. Phytanic acid intake was unrelated to the risk of localized disease. Our study provides evidence for the first time that increased consumption of phytanic acid may be associated with higher risks of advanced prostate cancer, and provides a putative mechanistic explanation for previously observed associations between red meat and dairy product consumption and prostate cancer risk. Citation Information: Cancer Prev Res 2008;1(7 Suppl):B131.

Abstract A80: Detection bias, statin drug use, and advanced prostate cancer risk

Abstract A80 Background Some previous prospective studies support that statin drugs (HMG Co-A reductase inhibitors) may protect against advanced prostate cancer. However, there is concern that these results may be due to detection bias. Men are likely to be screened for both elevated PSA and cholesterol by their internists, and thus are more likely to undergo both diagnostic workup for prostate cancer and be prescribed a statin. Therefore, men who take a statin may be less likely to be diagnosed with advanced prostate cancer, irrespective of a causal relation. Ideally, the possibility of this bias would be eliminated by studying the association between statin drugs and prostate cancer in an unscreened population, but because statins and PSA screening both became available at the same time (late 1980s), it is impossible to study this association in the pre-PSA era in the US. Thus, we performed a simulation to determine whether this source of detection bias is explanatory. Methods 3,000 datasets with 100,000 men without a prostate cancer diagnosis were simulated for two populations, one with a high (65%) and one with a low (15%) prevalence of PSA screening. For both populations we investigated three scenarios for the true association between statin use and advanced prostate cancer: RR=1.0, 0.75, and 0.5; in each we set the association for statin use and local disease to RR=1.0. We set the prevalence of statin use to 10% and varied the percentage of statins users who underwent PSA screening from 0 - 100%. We assumed the following: an annual prostate cancer incidence rate of 1%, a weighted average of the screened and unscreened men; a risk of prostate cancer diagnosis in screened men twice that in unscreened men; and an advanced stage at diagnosis in 20% and 40% of cases in screened and unscreened men, respectively. Results The observed association (RRobs) between statin use and local and total prostate cancer varied with the correlation between PSA screening and statin use. As PSA screening and statin use became more coincident, the RRobs between statin use and both local and total prostate cancer was biased upward from the true null association. This bias was stronger in the population with a low prevalence of PSA screening: e.g., assuming that 70% of men using statins had PSA screening, the RRobs for total and local prostate cancer, respectively, were 1.03 and 1.04 in the population with 65%, and 1.56 and 1.88 in the population with 15% prevalence of PSA screening. However, in all the simulated scenarios, there was very little bias in the RRobs for statin use and advanced prostate cancer: e.g., assuming that 70% of men using statins had PSA screening and that the true RR for advanced prostate cancer was 1.0, the RRobs for advanced prostate cancer was 0.98 in the population with a 65% prevalence of PSA screening, and 0.98 in the population with a 15% prevalence of PSA screening. Discussion Under the scenarios and assumptions we used, this simulation suggests that detection bias due to the correlation between PSA screening and statin use is unlikely to explain the inverse association observed between statin use and advanced prostate cancer in some US and European cohorts, but could account for the positive association for total prostate cancer that has been reported in some studies. Citation Information: Cancer Prev Res 2008;1(7 Suppl):A80.

Physical Activity in Relation to Total, Advanced, and Fatal Prostate Cancer

Physical activity has been inconsistently related to total prostate cancer and few studies have examined whether this association varies by disease aggressiveness. We examined physical activity in relation to total, advanced, and fatal prostate cancer in the NIH-AARP Diet and Health Study. At baseline (1995-1996), 293,902 men ages 50 to 71 years completed a questionnaire inquiring about current frequency of vigorous exercise of at least 20 min of duration, as well as frequency of exercise during adolescence (ages 15-18). We used proportional hazards regression to calculate multivariate relative risks (RR) and 95% confidence intervals (95% CI). During up to 8.2 years of follow-up, 17,872 prostate cancer cases were identified, including 1,942 advanced and 513 fatal cases. Comparing frequent (5+ times per week) versus infrequent (less than once per week) vigorous exercise, exercise at baseline was not associated with risk of total prostate cancer (RR, 1.01; 95% CI, 0.96-1.07; P(trend) = 0.78), advanced prostate cancer (RR, 1.14; 95% CI, 0.97-1.33; P(trend) = 0.25), or fatal prostate cancer (RR, 0.90; 95% CI, 0.67-1.20; P(trend) = 0.12). Increasing level of vigorous exercise during adolescence was associated with a small 3% reduction in total prostate cancer risk (frequent versus infrequent exercise during adolescence: RR, 0.97; 95% CI, 0.91-1.03; P(trend) = 0.03) but was not associated with risk of advanced prostate cancer (RR, 0.95; 95% CI, 0.78-1.14; P(trend) = 0.18) or fatal prostate cancer (RR, 0.96; 95% CI, 0.67-1.36; P(trend) = 0.99). Neither vigorous exercise at baseline nor exercise during adolescence was related to risk of total, advanced, or fatal prostate cancer in this large prospective cohort.

Cholesterol and Cholesterol-Rich Membranes in Prostate Cancer: An Update

Cells maintain normal structure and function by responding appropriately to cues from the surrounding milieu. Extracellular stimuli are transduced from the surface through the plasma membrane by a complex series of interactions between ligands, their receptors and intracellular signaling partners (e.g., kinases, G proteins). Cholesterol-enriched membrane microdomains, generally referred to as "lipid rafts", exist within the lipid bilayer of all mammalian cells and play an important role in signaling from the cell surface to various subcellular compartments. Lipid rafts have also been implicated in tumor growth and aggressiveness. Epidemiological evidence suggests that the modern Western diet, which contains substantial levels of cholesterol and other fatty substances, promotes prostate cancer progression. Consistent with this idea, prolonged inhibition of the cholesterol synthesis pathway by pharmacologic intervention in men has recently been associated with reduction in risk of advanced prostate cancer. In this review, we discuss the possibility that membrane cholesterol promotes prostate cancer progression by a mechanism that involves dysregulation of lipid raft-resident signaling complexes. This hypothesis provides new avenues for mechanistic studies as well as therapeutic intervention.

Common 8q24 Sequence Variations Are Associated with Asian Indian Advanced Prostate Cancer Risk

Three sequence variations (rs1447295, rs16901979, and rs6983267) on 8q24 were recently shown to independently affect prostate cancer risk. Asian Indians have a low prostate cancer risk; however, in the absence of screening practices for the disease, most are diagnosed with metastatic prostate cancer. We evaluated the association of these single nucleotide polymorphisms (SNP) with advanced prostate cancer in 153 prostate cancer cases and 227 age-matched controls (northern India). Overall, there was a positive association between carriers of the allele A of rs1447295 and prostate cancer risk [odds ratio (OR), 1.60; 95% confidence interval (95% CI), 1.01-2.52] but no significant association with carriers of alleles A of rs16901979 and allele G of rs6983267. However, significant associations were observed for both SNPs in men with high Gleason scores (>/=7) and metastasis. Adjusting for age, the ORs were 1.77 (95% CI, 1.05-2.97) for carriers of rs1447295 A and 1.85 (95% CI, 1.04-3.28) for carriers of the rs16901979 A allele. We also observed significant joint effects among these loci associated with prostate cancer risk and severity, suggestive of additive effects of the independent SNPs. The ORs for the combined effects of rs1447295 A with rs16901979 A or rs6983267 G were 2.61 (95% CI, 1.11-6.12) and 1.84 (95% CI, 1.12-3.06), respectively. There was no joint effect between SNPs rs16901979 A and rs6983267 G. These results confirm the significance of these SNPs in prostate cancer etiology in a previously unstudied population who do not undergo prostate cancer screening and are diagnosed with severe disease.

A genetic polymorphism of the osteoprotegerin gene is associated with an increased risk of advanced prostate cancer

BackgroundThe purpose of this study was to evaluate the role of osteoprotegerin gene (OPG) polymorphisms as genetic modifiers in the etiology of prostate cancer (PCa) and disease progression.MethodsThree hundred and sixty one patients with PCa and 195 normal controls were enrolled in the study, and two genetic polymorphisms, 149 T/C and 950 T/C in the putative promoter region of OPG, were genotyped.ResultsThere was no significant difference in the genotype frequencies between PCa patients and controls (P = 0.939 and 0.294 for 149 T/C and 950 T/C polymorphisms, respectively). However, those patients with TC and TT genotypes in the 950 T/C polymorphism had a significantly increased risk of extraprostatic (age-adjusted odds ratio; aOR = 1.74 and 2.03 for TC and TT genotypes compared with the CC genotype, P = 0.028) and metastatic disease (aOR = 1.72 and 2.76 for TC and TT genotypes compared with the CC genotype, P = 0.009) compared with those with the CC genotype. In addition, analysis of the metastatic PCa patients (Stage D) showed that the presence of the T allele of the OPG 950 T/C polymorphism was an independent risk factor predicting survival by Cox proportional hazard regression analyses (P = 0.031).ConclusionProgression of PCa may be influenced by an intrinsic genetic factor of the host's bone metabolism. The variant C allele of 950 T/C in the OPG promoter may play a major role as a genetic safe guard against progression in patients with PCa.

CDKN1B V109G Polymorphism Frequency and Prostate Cancer Risk in Taiwan

Aim: The CDKN1B (p27) V109G polymorphism has been suggested to confer the risk of advanced prostate cancer in Caucasian males. However, its prevalence in Asian populations has never been reported. The aim of this study was to determine the CDKN1B V109G polymorphism frequency in the low incidence Taiwanese population and investigate its potential role on prostate cancer susceptibility and disease progression. Methods: A hospital-based case-control study was conducted, which enrolled a total of 190 prostate cancer patients and 292 age-matched male controls. PCR-RFLP was used to determine the CDKN1B V109G polymorphism. The association between CDKN1B V109G and prostate cancer risk and clinicopathologic variables was analyzed. Results: The variant CDKN1B G allele frequency in Taiwanese males appears to be low (2.1%). Overall, there was no significant association between CDKN1B V109G polymorphism and prostate cancer risk. Similarly, no significant findings were found when further stratified by different age groups, disease stages, and pathological grades. In terms of disease outcome, the CDKN1B V109G genotypes were not associated with either hormone response status after hormone therapy (p = 0.730) or with prostate-specific antigen recurrence for clinically localized prostate cancer patients who receive radical prostatectomy (p = 0.536). Conclusions: There was a low prevalence of CDKN1B V109G polymorphism in Taiwanese compared to Caucasian males. Hence, it may not be an appropriate biomarker of prostate cancer among the Taiwanese population. Further large-scale studies are needed to clarify the role of CDKN1B V109G polymorphism on prostate cancer risk.

Statin use and the risk of prostate cancer: A metaanalysis of 6 randomized clinical trials and 13 observational studies

Statins have been suggested to prevent prostate cancer. Our aim was to examine statin use in relation to both total prostate cancer and the more clinically important advanced prostate cancer, through a detailed metaanalysis of the epidemiologic studies published on the subject in peer-reviewed literature. A comprehensive search for articles published up to November 2007 was performed, reviews of each study were conducted and data were abstracted. Prior to metaanalysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using the random-effects model. Subgroup and sensitivity analyses were also performed. Nineteen studies [6 randomized clinical trials (RCTs), 6 cohort and 7 case-control studies] contributed to the analysis. There was no evidence of an association between statin use and total prostate cancer among either RCTs (RR = 1.06, 95% CI: 0.93-1.20) or the observational studies (RR = 0.89, 95% CI: 0.65-1.24). However, high heterogeneity was detected among the observational studies. Moreover, long-term statin use did not significantly affect the risk of total prostate cancer (RR = 0.93, 95% CI: 0.77-1.13). In contrast, synthesis of the available reports that had specifically examined statin use in relation to advanced prostate cancer indicated a protective association (RR = 0.77, 95% CI: 0.64-0.93). Our results do not support the hypothesis that statins reduce the risk of total prostate cancer. However, further research is required to investigate whether the particular association of statin use with lower risk of advanced prostate cancer is indeed causal.

Review of recent evidence in support of a role for statins in the prevention of prostate cancer

We examine the potential chemopreventive role statins may have in prostate cancer, highlight the basic science supporting this role and analyze the human data regarding the association between statin use and prostate cancer. Basic scientific evidence suggests that, through cholesterol and noncholesterol-mediated mechanisms, statins inhibit many pathways of cancer formation and progression. A handful of observational studies found statin use was associated with reduced prostate cancer risk, though others found no association. In the last year, however, four large prospective studies have observed similar reductions in the risk of advanced prostate cancer with essentially no reduction in the risk of overall prostate cancer. This may, in part, explain why previous studies, including large metaanalyses of clinical trials of statins in the prevention of cardiovascular outcomes, did not observe any association between statin use and overall prostate cancer risk. The exact association between statin medication use and prostate cancer, and whether this association is causal in nature, remains unclear. Recent evidence, however, is encouraging, particularly for reducing the risk of advanced disease. Thus, while at present there are insufficient data to recommend all men start taking a statin medication regardless of their cholesterol profile, the rationale to move forward with further research is clear.

Rationale for statins in the chemoprevention of prostate cancer

The potential ability of statin medications to prevent cancer has recently received considerable attention. Of all cancers studied, data for prostate cancer are the most promising. Results from studies examining the association between statin use and reduced risk of prostate cancer have been encouraging, particularly in terms of advanced prostate cancer risk. These findings are supported by a strong foundation of scientific evidence demonstrating the potential cholesterol and non-cholesterol-mediated mechanisms through which statins may prevent prostate cancer. In this article, we analyze recent human data regarding the association between statins and prostate cancer, and the basic scientific data supporting the possible antineoplastic mechanisms of statins. We also address the issue of where to best direct future funding and research energies. There is currently insufficient evidence to recommend all men to initiate therapy with a statin medication regardless of cholesterol profile, but the rationale to move forward with research is clear.

Polymorphisms in Angiogenesis-Related Genes and Prostate Cancer

Angiogenesis is required for development and progression of prostate cancer. Potentially functional single nucleotide polymorphisms (SNP) in genes important in prostate angiogenesis (VEGF, HIF1A, and NOS3) have previously been associated with risk or severity of prostate cancer. Prostate cancer cases (n = 1,425) and controls (n = 1,453) were selected from the Cancer Prevention Study II Nutrition Cohort. We examined associations between 58 SNPs in nine angiogenesis-related candidate genes (EGF, LTA, HIF1A, HIF1AN, MMP2, MMP9, NOS2A, NOS3, VEGF) and risk of overall and advanced prostate cancer. Unconditional logistic regression was used to estimate odds ratios, adjusted for matching factors. Our results did not replicate previously observed associations with SNPs in VEGF, HIF1A, or NOS3, nor did we observe associations with SNPs in EGF, LTA, HIF1AN, MMP9, or NOS2A. In the MMP2 gene, three intronic SNPs, all in linkage disequilibrium, were associated with overall and advanced prostate cancer (for overall prostate cancer, P(trend) = 0.01 for rs1477017, P(trend) = 0.01 for rs17301608, P(trend) = 0.02 for rs11639960). However, two of these SNPs (rs17301608 and rs11639960) were examined and were not associated with prostate cancer in a recent genome-wide association study using prostate cancer cases and controls from the Prostate, Lung, Colorectal, and Ovary study cohort. Furthermore, when we pooled our results for these two SNPs with those from the Prostate, Lung, Colorectal, and Ovary cohort; neither SNP was associated with prostate cancer. None of the SNPs examined seem likely to be importantly associated with risk of overall or advanced prostate cancer.

Dietary intake of vitamin K and risk of prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg)

BackgroundAnticarcinogenic activities of vitamin K have been observed in various cancer cell lines, including prostate cancer cells. Epidemiologic studies linking dietary intake of vitamin K with the development of prostate cancer have not yet been conducted. ObjectiveWe evaluated the association between dietary intake of phylloquinone (vitamin K1) and menaquinones (vitamin K2) and total and advanced prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition. DesignAt baseline, habitual dietary intake was assessed by means of a food-frequency questionnaire. Dietary intake of phylloquinone and menaquinones (MK-4–14) was estimated by using previously published HPLC-based food-content data. Multivariate-adjusted relative risks of total and advanced prostate cancer in relation to intakes of phylloquinone and menaquinones were calculated in 11 319 men by means of Cox proportional hazards regression. ResultsDuring a mean follow-up time of 8.6 y, 268 incident cases of prostate cancer, including 113 advanced cases, were identified. We observed a nonsignificant inverse association between total prostate cancer and total menaquinone intake [multivariate relative risk (highest compared with lowest quartile): 0.65; 95% CI: 0.39, 1.06]. The association was stronger for advanced prostate cancer (0.37; 0.16, 0.88; P for trend = 0.03). Menaquinones from dairy products had a stronger inverse association with advanced prostate cancer than did menaquinones from meat. Phylloquinone intake was unrelated to prostate cancer incidence (1.02; 0.70, 1.48). ConclusionsOur results suggest an inverse association between the intake of menaquinones, but not that of phylloquinone, and prostate cancer. Further studies of dietary vitamin K and prostate cancer are warranted.

Cholesterol-lowering drugs might reduce the risk of advanced prostate cancer

Cholesterol-lowering drugs might reduce the risk of advanced prostate cancer

Height, Urban-born and Prostate Cancer Risk in Japanese Men

Height and early-life environments have received attention as risk factors for prostate cancer. However, the evidence is sparse in Japan. To elucidate the associations of height and early-life factors with prostate cancer risk in Japanese men, we conducted a hospital-based case-control study. In addition, to investigate whether the associations vary between prostate cancer and other major cancers, we conducted a comparative study within the same case-control study. Study subjects consisted of 282 prostate cancer cases, 584, 461, 231, and 156 male stomach, lung, colon and rectal cancer cases, respectively, and 1730 male hospital controls, aged 50 and over admitted to a single hospital in Miyagi Prefecture from 1997 to 2003. Information on height and early-life factors including birthplace and stature at 12 years was collected using a self-administered questionnaire. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated for each exposure variable. A significant positive association was found between height and prostate cancer risk (OR, 1.52; 95% CI, 1.00-2.31, between the highest and lowest quartiles; P for trend = 0.03). A significant association of urban-born with prostate cancer risk was also found (OR, 1.48; 95% CI, 1.03-2.13). Analyses by stage revealed that height might be more strongly associated with the risk of advanced prostate cancer. For other major cancers, no significant association with height and early-life factors was observed. Height and early-life factors were significantly associated with prostate cancer risk. Compared with other major cancers, these associations were specific to prostate cancer.

Circulating Concentrations of Folate and Vitamin B12 in Relation to Prostate Cancer Risk: Results from the European Prospective Investigation into Cancer and Nutrition Study

Determinants of one-carbon metabolism, such as folate and vitamin B(12), have been implicated in cancer development. Previous studies have not provided conclusive evidence for the importance of circulating concentrations of folate and vitamin B(12) in prostate cancer etiology. The aim of the present study was to investigate the relationship between prostate cancer risk and circulating concentrations of folate and vitamin B(12) in a large prospective cohort. We analyzed circulating concentrations of folate and vitamin B(12) in 869 cases and 1,174 controls, individually matched on center, age, and date of recruitment, nested within the European Prospective Investigation into Cancer and Nutrition cohort. Relative risks (RR) for prostate cancer were estimated using conditional logistic regression models. Overall, no significant associations were observed for circulating concentrations of folate (P(trend) = 0.62) or vitamin B(12) (P(trend) = 0.21) with prostate cancer risk. RRs for a doubling in folate and vitamin B(12) concentrations were 1.03 [95% confidence interval (95% CI), 0.92-1.16] and 1.12 (95% CI, 0.94-1.35), respectively. In the subgroup of cases diagnosed with advanced stage prostate cancer, elevated concentrations of vitamin B(12) were associated with increased risk (RR for a doubling in concentration, 1.69; 95% CI, 1.05-2.72, P(trend) = 0.03). No other subgroup analyses resulted in a statistically significant association. This study does not provide strong support for an association between prostate cancer risk and circulating concentrations of folate or vitamin B(12). Elevated concentrations of vitamin B(12) may be associated with an increased risk for advanced stage prostate cancer, but this association requires examination in other large prospective studies.

8q24 and prostate cancer: association with advanced disease and meta-analysis

Compelling evidence demonstrates chromosome 8q24 as a prostate cancer susceptibility locus. Multiple variants within three adjacent regions at 8q24 have recently been identified to impact the risk of prostate cancer. Yet, the role of these variants in more advanced disease has not been rigorously assessed. To examine the relationship between 8q24 variants and advanced disease, we tested 10 previously associated 8q24 variants in a case-control study of advanced prostate cancer (N=1012). Of these ten 8q24 variants, six were associated with the risk of advanced prostate cancer (P=0.001-0.038). Three of these variants (rs10090154-region 1, rs16901979-region 2, and rs6983267-region 3), each variant residing in one of the three previously reported 8q24 regions, could account for our 8q24 effects on advanced disease. A meta-analysis across 10 studies including our results of four 8q24 variants (rs1442295 and DG8S737-region 1, rs16901979-region 2, and rs6983267-region 3) and prostate cancer risk demonstrated strong associations across a wide array of study designs and populations. Our findings provide the first confirmation that the three 8q24 regions independently influence the risk of prostate cancer and, in particular, advanced disease.