Lycopene intake and prostate cancer risk in men at high cardiovascular risk: a prospective cohort study

Risk Factors for Prostate Cancer in Men Aged Less Than 60 Years: A Case–Control Study from Italy

<p>Tables S1-S7. Table S1. Characteristics of all cases and population controls in the NCI Maryland Prostate Cancer Case-Control Study. Table S2. Pain reliever use of participants in the NCI Maryland Prostate Cancer Case-Control Study. Table S3. Adjusteda odds ratios and 95% confidence intervals for associations of regular aspirin use and prostate cancer risk in the NCI Maryland Prostate Cancer Case-Control Study. Table S4. Adjusteda odds ratios and 95% confidence intervals for associations of regular aspirin use and prostate cancer risk in men with low stageb disease compared to population controls. Table S5. Adjusteda odds ratios and 95% confidence intervals for associations of regular aspirin use and prostate cancer risk in men with high stageb disease compared to controls. Table S6. Adjusteda odds ratios and 95% Confidence intervals for associations of regular aspirin use and prostate cancer risk in men with aggressiveb disease compared to population controls. Table S7. Adjusteda odds ratios and 95% confidence intervals for associations of regular aspirin use and prostate cancer risk in men with nonaggressiveb disease compared to populations controls.</p>

Circulating 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with both higher and lower risk of prostate cancer (PCa), whereas elevated levels of circulating calcium has been related to higher risks. However, there are few studies that account for effects of both calcium and 25(OH)D concentrations on incident PCa in a black population. We examined these relationships in a case–control study of men 40–80 years old with newly diagnosed, histologically confirmed PCa in Jamaica, a tropical country. Mean serum calcium concentrations was higher among cases (2.32 ± 0.19 mmol/L) than controls, (2.27 ± 0.30 mmol/L) (P = 0.023) however, there were no differences in 25(OH)D by cancer status (cases, 33.67 ± 12.71 ng/mL; controls (32.25 ± 12.59 ng/mL). Serum calcium was not correlated with 25(OH)D (partial correlation: r, 0.06; P = 0.287). Multivariable-adjusted models showed a positive linear relationship between PCa and serum calcium (OR, 1.12; CI, 1.00–1.25 per 0.1 nmol/L). Serum 25(OH)D concentration also showed a positive association with PCa (OR, 1.23; CI, 1.01–1.49 per 10 ng/mL). The odds of PCa in men with serum 25(OH)D tertile 2 was OR, 2.18; CI, 1.04–4.43 and OR, 2.47 CI, 1.20–4.90 for tertile 3 (Ptrend = 0.013). Dietary intakes of calcium showed no relationship with PCa. Despite the strong relationship between serum calcium and vitamin D the mechanism by which each affects prostate cancer risk in men of African ancestry needs additional investigation.

Advanced but Not Localized Prostate Cancer is Associated With Increased Oxidative Stress

Prostate cancer is the most common non-cutaneous cancer and second leading cause of cancer death among men in the U.S. Although ecologic and migrant studies suggest that diet plays a role in the etiology of prostate cancer, few specific nutrients that alter its occurrence have been identified in case-control and cohort studies. Phytoestrogens are a family of bioactive compounds that are abundant in soy products and some other food groups (e.g. legumes and chick peas). Experimental studies revealed that phytoestrogen intake may modulate the risk of prostate cancer due to their structural similarity to 17β-estradiol and the resulting competitive binding to estrogen receptors. Despite biological plausibility, it still remains elusive whether phytoestrogen intake influences prostate cancer risk in human populations. Therefore, the objective of the present study was to investigate the associations between dietary intake of phytoestrogens and the risk of total and advanced prostate cancer among 30,097 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). A total of 3628 cases of prostate cancer (including 396 advanced cases) have been documented during a median follow up of 11.5 years. Advanced prostate cancer were defined as stage II cancer with a Gleason score of ≥8, or stage III or stage IV cancer. Dietary intake of phytoestrogens was assessed with a validated food frequency questionnaire. Cox proportional hazards regression was performed to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for dietary intake of phytoestrogens in relation to prostate cancer risk. After adjustment for confounders, an increased risk of advanced prostate cancer was found for the higher dietary intake of isoflavones (HR: 1.58; 95% CI: 1.11, 2.24), genistein (HR: 1.42; 95% CI: 1.02, 1.98), daidzein (HR: 1.62; 95% CI: 1.13, 2.32), and glycitein (HR: 1.53; 95% CI: 1.09, 2.15). Conversely, it appears that the higher dietary intake of genistein was associated with a reduced risk of non-advanced prostate cancer (HR: 0.88; 95% CI: 0.78, 0.99) and total prostate cancer (HR: 0.90; 95% CI: 0.81, 1.00). The risk estimates presented above were obtained for comparisons between the quintile 5 and quintile 1 of respective phytoestrogen intake. In summary, our analysis of this national prospective cohort study suggests that dietary intake of phytoestrogens modulated the risk of prostate cancer and that some of these effects may differ by the aggressiveness of the disease. Citation Format: Michael Reger, Terrell Zollinger, Ziyue Liu, Josette Jones, Jianjun Zhang. Dietary intake of phytoestrogens and the risk of prostate cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1884. doi:10.1158/1538-7445.AM2015-1884

Prostate cancer is one of the most frequent malignancies in the world, with significant morbidity and death rates. Identifying novel biomarkers is critical to reducing morbidity and mortality from the illness today. Although lipids have been linked to an increased risk of prostate cancer, it is unclear if the non-high-density lipoprotein cholesterol (NHDL-C) to high-density lipoprotein cholesterol (HDL-C) ratio (NHHR) is related to prostate cancer. Therefore, we assessed the relationship between NHHR and prostate cancer risk. This study comprised 1,718 individuals who attended the First Affiliated Hospital of Xinjiang Medical University between March 2020 and March 2024. A pathological examination of a prostate puncture biopsy was utilized to confirm the diagnosis of prostate cancer. The study collected information on participants' clinical and laboratory examinations, used propensity score matching to eliminate potential confounders, and analyzed the relationship between NHHR and prostate cancer, using logistic regression models combined with restricted cubic spline (RCS) and receiver operating characteristic (ROC) curve. Furthermore, sensitivity analyses were undertaken to assess the robustness of the results. (1) There were statistically significant differences in neutrophils, erythrocytes, triglycerides, alkaline phosphatase, and NHHR between the two groups; (2) after adjusting for all covariates, logistic regression revealed a negative association between NHHR and prostate cancer (0.91 (0.83∼0.99), P=0.028). Participants in the second quartile had a significantly lower risk of prostate cancer after comprehensive adjustment (0.69 (0.50∼0.96), P=0.026); (3) the restrictive cubic spline curve shows a non-linear relationship between NHHR and prostate cancer risk, with a turning point of 1.824; (4) the results of the ROC curve showed that the NHHR had an area under the curve (AUC) of 0.73; the results of the decision curve suggested that the model was able to provide a high benefit value for patients, with a threshold range of approximately 0.01-0.98 and a maximum net benefit of 0.52, and the calibration curve demonstrated that the model was accurate and reliable. There is a non-linear dose-response relationship between NHHR and prostate cancer risk, which may be associated with a reduced risk of prostate cancer. The finding can be used to detect high-risk groups and prevent prostate cancer.

MP09-20 THE COMBINATION OF HISTOLOGICAL PROSTATE ATROPHY AND INFLAMMATION IS ASSOCIATED WITH LOWER RISK OF PROSTATE CANCER

Prostate cancer (PCa) is a common illness for aging males. Lycopene has been identified as an antioxidant agent with potential anticancer properties. Studies investigating the relation between lycopene and PCa risk have produced inconsistent results. This study aims to determine dietary lycopene consumption/circulating concentration and any potential dose–response associations with the risk of PCa. Eligible studies published in English up to April 10, 2014, were searched and identified from Pubmed, Sciencedirect Online, Wiley online library databases and hand searching. The STATA (version 12.0) was applied to process the dose–response meta-analysis. Random effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs) and to incorporate variation between studies. The linear and nonlinear dose–response relations were evaluated with data from categories of lycopene consumption/circulating concentrations. Twenty-six studies were included with 17,517 cases of PCa reported from 563,299 participants. Although inverse association between lycopene consumption and PCa risk was not found in all studies, there was a trend that with higher lycopene intake, there was reduced incidence of PCa (P = 0.078). Removal of one Chinese study in sensitivity analysis, or recalculation using data from only high-quality studies for subgroup analysis, indicated that higher lycopene consumption significantly lowered PCa risk. Furthermore, our dose–response meta-analysis demonstrated that higher lycopene consumption was linearly associated with a reduced risk of PCa with a threshold between 9 and 21 mg/day. Consistently, higher circulating lycopene levels significantly reduced the risk of PCa. Interestingly, the concentration of circulating lycopene between 2.17 and 85 μg/dL was linearly inversed with PCa risk whereas there was no linear association >85 μg/dL. In addition, greater efficacy for the circulating lycopene concentration on preventing PCa was found for studies with high quality, follow-up >10 years and where results were adjusted by the age or the body mass index. In conclusion, our novel data demonstrates that higher lycopene consumption/circulating concentration is associated with a lower risk of PCa. However, further studies are required to determine the mechanism by which lycopene reduces the risk of PCa and if there are other factors in tomato products that might potentially decrease PCa risk and progression.

BackgroundCurrent evidence on risk of prostate cancer following a diagnosis of male breast cancer is limited and guidance for screening in this potentially higher-risk population remainsunclear. Our objective was to quantify prostate cancer risk in men diagnosed with breast cancer.MethodsWe identified men diagnosed with first primary breast cancer between 1988 and 2012 using the Surveillance, Epidemiology and End Results Program registry databases. Men were followed for occurrence of a second primary prostate cancer and secondary outcomes of cancer-specific and overall survival. Stratified analyses were performed by age, breast cancer stage, race, and breast cancer hormone receptor status. Excess risk per 10,000 person-years and standardized incidence ratios (SIR) with 95% confidence intervals (95% CI) were calculated. We used multivaraible Cox proportional hazard models to estimate hazard ratios (HR) and 95% CI for characteristics associated with secondary prostate cancer and survival.ResultsFrom a cohort of 5753 men with breast cancer with median follow up of 4.3 years, we identified 250 cases of second primary prostate cancer. Overall, the incidence of second primary prostate cancer was modestly greater than expected (SIR = 1.12, 95% CI 0.93–1.33), although not statistically significant. Stratified analyses demonstrated associations for men ages 65–74 at the time of breast cancer diagnosis (SIR = 1.34, 95%CI 1.01–1.73), hormone receptor-positive breast cancer (SIR = 1.23, 95%CI 1.11–1.39) or AJCC stage I breast cancer (SIR = 1.36, 95%CI 1.04–1.75) and second primary prostate cancer diagnosis.ConclusionsThe incidence of prostate cancer in men with history of breast cancer is similar to the general population. Men with favorable characteristics of their breast cancer were more likely to develop prostate cancer, possibly due to a lower competing risk of breast cancer mortality.

Oxidative Stress Measured by Urine F2-Isoprostane Level is Associated With Prostate Cancer

<div>Abstract<p>Prostate cancer risk is influenced by rare and common germline variants. We examined the aggregate association of rare germline pathogenic/likely pathogenic/deleterious (P/LP/D) variants in <i>ATM, BRCA2, PALB2,</i> and <i>NBN</i> with a polygenic risk score (PRS) on prostate cancer risk among 1,796 prostate cancer cases (222 metastatic) and 1,424 controls of African ancestry. Relative to P/LP/D non-carriers at average genetic risk (33%–66% of PRS), men with low (0%–33%) and high (66%–100%) PRS had Odds Ratios (ORs) for overall prostate cancer of 2.08 [95% confidence interval (CI) = 0.58–7.49] and 18.06 (95% CI = 4.24–76.84) among P/LP/D carriers and 0.57 (95% CI = 0.46–0.71) and 3.02 (95% CI = 2.53–3.60) among non-carriers, respectively. The OR for metastatic prostate cancer was 2.73 (95% CI = 0.24–30.54) and 28.99 (95% CI = 4.39–191.43) among P/LP/D carriers and 0.54 (95% CI = 0.31–0.95) and 3.22 (95% CI = 2.20–4.73) among non-carriers, for men with low and high PRS, respectively. Lifetime absolute risks of overall prostate cancer increased with PRS (low to high) from 9.8% to 51.5% in P/LP/D carriers and 5.5% to 23.9% in non-carriers. Lifetime absolute risks of metastatic prostate cancer increased with PRS from 1.9% to 18.1% in P/LP/D carriers and 0.3% to 2.2% in non-carriers These findings suggest that assessment of prostate cancer risk for rare variant carriers should include PRS status.</p>Significance:<p>These findings highlight the importance of considering rare and common variants to comprehensively assess prostate cancer risk in men of African ancestry.</p></div>

Use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAID), particularly long-term use, has been associated with modestly reduced risk of prostate cancer in previous epidemiologic studies. Acetaminophen, a commonly used pain reliever, is not traditionally considered an NSAID but can have anti-inflammatory effects. Few studies have examined the association between long-term acetaminophen use and prostate cancer incidence. We examined the association between acetaminophen use and prostate cancer incidence among 78,485 men in the Cancer Prevention Study II Nutrition Cohort. Information on acetaminophen use was obtained from a questionnaire completed at study enrollment in 1992 and updated by using follow-up questionnaires in 1997 and every two years thereafter. Relative risks (RR) were estimated by using proportional hazards regression models. All models were adjusted for age, race, education, body mass index, diabetes, NSAID use, and history of prostate-specific antigen testing. During follow-up from 1992 through 2007, 8,092 incident prostate cancer cases were identified. Current regular use of acetaminophen (30 or more pills per month) for 5 or more years was associated with lower risk of overall prostate cancer (RR = 0.62, 95% CI: 0.44-0.87) and aggressive prostate cancer (RR = 0.49, 95% CI: 0.27-0.88). Current regular use of less than 5 years duration was not associated with prostate cancer risk. These results suggest that long-term regular acetaminophen use may be associated with lower prostate cancer risk. If the association between acetaminophen use and lower risk of prostate cancer is confirmed, it could provide clues about biological mechanisms that are important in prostate carcinogenesis.

Background - There is suggestive evidence of familial clustering of breast and prostate cancer in first-degree relatives; women with a family history of prostate cancer are at increased risk of breast cancer. Few studies have investigated joint family history of breast and prostate cancer and prostate cancer risk, and no study to date has examined lethal prostate cancer. Methods - We studied 42,672 from the Health Professionals Follow-up Study between 1996 to 2012. During follow-up, 4,258 prostate cancer cases were diagnosed, of whom 380 were lethal disease. Men self-reported family history of breast and prostate cancer, including in siblings or parents. Using cause-specific hazards regression, we estimated hazard ratios (HR) and 95% confidence intervals (CI) of the association between family history and prostate cancer risk and progression. Results - About 8% of men had a family history of prostate cancer, 8.7% had a family history of breast cancer, and 1.4% of men had a family history of both breast and prostate cancer. A family history of prostate cancer was significantly associated with an increased risk of prostate cancer (HR: 1.69; 95% CI: 1.54-1.85). Increased risk was higher for men with a father diagnosed with prostate cancer (HR: 1.64 95% CI: 1.49-1.80) than for men with a diagnosis in a brother(s) (HR: 1.51 95% CI: 1.27-1.80). A positive family history of breast cancer was associated with a small, but significant 22% increased risk (HR: 1.22; 95% CI: 1.11-1.35). Familial breast cancer in a sister (HR: 1.22 95% CI: 1.06-1.41) increased risk more than familial breast cancer in a mother (HR: 1.12; 95% CI: 0.99-1.25). Men with a family history of both prostate and breast cancer had a 52% (HR: 1.52; 95%CI: 1.23-1.88) increased risk of prostate cancer compared to men with no family history of either cancer. Risk of lethal prostate cancer was also significantly increased for men with a positive family history of prostate cancer (HR: 1.64; 95% CI: 1.20-2.24), as well as for men with a family history of breast cancer (HR: 1.47; 95% CI: 1.07-2.01). Conclusions - These results support the findings of familial aggregation of breast and prostate cancer, and for the first time suggest an association between familial breast cancer and lethal prostate cancer. Data from this prospective study have translational relevance for family counseling of cancer patients. Citation Format: Lauren E. Barber, Travis A. Gerke, Sarah C. Markt, Giovanni Parmigiani, Lorelei A. Mucci. A family affair: Prostate cancer risk and family history of breast or prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2543.

Soy is a major plant source of dietary protein to humans. Epidemiologic studies show that soy consumption may be associated with a reduction in cancer risk in humans. The purpose of this study was to conduct a meta‐analysis on the association between soy and prostate cancer in men. We systematically reviewed studies obtained through a thorough MEDLINE literature search and identified 15 studies on soy consumption and eight on isoflavone intake in relation to prostate cancer risk. We conducted this analysis using a random‐effects model in which studies with smaller standard error of estimate are given greater weight in the summary measure. Our analysis of studies on soy intake yielded an overall risk estimate of 0.74 (95% confidence interval: 0.63, 0.89; P = 0.001). When separately analyzed, studies on non‐fermented soy foods yielded an overall risk estimate of 0.70 (0.56, 0.88; P = 0.002) and those on fermented ones yielded 1.02 (0.73, 1.42; P = 0.922). The analysis of studies on isoflavones yielded an overall risk estimate of 0.88 (0.76, 1.02; P = 0.085). When analyzed on the basis of daily isoflavone intakes, we found an overall risk estimate of 0.63 (0.41, 0.96; P = 0.03) from studies at mg/day and 0.99 (0.85, 1.16; P = 0.909) from those at µg/day, respectively. Results of this analysis suggest that consumption of soy foods is associated with a reduction in prostate cancer risk in men.

Soy foods have been part of traditional Asian diets for many centuries, while soy products were introduced in Western countries only a few decades ago. Migrants from Asia maintained their food habits to a certain degree when they moved to the U.S., but they also adopted Western foods (1). Inspired by studies among migrants and by the low incidence rates for several cancers among Asians, research into the protective effects of isoflavones in soy foods was initiated. Due to their estrogen-like structure, much of the research has focused on hormone-dependent cancers, i.e., breast, endometrial, ovarian, and prostate cancer, but some work on colorectal cancer has also been performed. During years of experimental and epidemiologic research, it has become evident that not all populations may derive the same benefit from consuming soy foods. One of the more consistent findings in soy research is the fact that epidemiologic studies report a stronger protective effect of soy foods against breast cancer among women who grew up in Asian countries and in those who consumed soy foods throughout childhood and adolescence (2). This presentation will focus on epidemiologic studies that have investigated the association between soy foods and cancer risk among populations with different ethnic backgrounds. In addition, some underlying mechanisms that may be responsible for ethnic differences, such as intestinal equol production, genetic polymorphisms, and timing of exposure will be discussed. Epidemiologic studies among women of Asian, primarily Japanese and Chinese, ancestry show a more consistent protective effect against breast cancer than investigations among Western populations; the odds ratio (OR) was 0.71 (95% CI: 0.60-0.85) among Asians when the highest and lowest intake group were compared, while soy food was unrelated to breast cancer risk in Western studies (OR = 1.04; 95%CI: 0.97-1.11) (2). Similarly, a meta-analysis of prostate cancer studies found a lower risk associated with soy consumption only among Asian (OR = 0.52; 95%CI: 0.33-0.81) but not Western populations (OR = 0.99; 95% CI: 0.85-1.16) (3). On the other hand, meta-analyses for endometrial, ovarian, and colorectal cancer described only small differences in associations by ethnicity (4, 5). Recent case-control analyses nested within the Multiethnic Cohort in Hawaii and Los Angeles examined urinary isoflavone excretion as a biomarker of soy intake and reported similar results for breast but not prostate cancer. While the risk associated with breast cancer was 0.69 (95% CI: 0.51-0.92) among Japanese Americans and 0.98 (95% CI: 0.61-1.55) among Caucasians (6), the risk estimates did not differ by ethnicity for prostate cancer (7). Evidence from observational and intervention studies also suggests possible differential effects of soy intake on biomarkers of breast cancer risk (8-10), e.g., mammographic density and concentrations of serum estrogens and testosterone, urinary estrogen metabolite patterns, IGF-I, and PSA. Whereas the higher intake and possibly the type of soy foods in Asian populations may explain the observations for breast and prostate cancer risk (11), bioavailability of bioactive substances may also be a contributing factor (12). For example, the capacity of the intestinal bacteria to metabolize the isoflavone dadzein into the metabolite equol varies across populations and may confer a greater protection against disease than the other isoflavonoids (13, 14). Another reason that not all individuals may benefit from soy food exposure to the same degree is genetic variation. Genetic polymorphisms may alter enzyme activity or modulate the expression of genes involved in pathways influenced by isoflavones and relevant to cancer risk. Menopausal status, obesity, and other dietary components are other causes for isoflavones to exert differential actions across populations. Alternatively, the overall effect of soy foods on carcinogenesis may depend on the time of life when isoflavones were administered because isoflavones have estrogenic and anti-estrogenic effects. A number of case-control studies that assessed soy intake during childhood or adolescence found a stronger protection for early life than adult soy intake. Since experimental studies indicate that estrogen exposure in young animals induces protection against cancer development, the weak estrogenic effects of isoflavones in soy beans, if consumed early in life, may achieve or accelerate differentiation of breast tissue structures similar to an early pregnancy and, thereby, make the tissue less susceptible to carcinogens and prevent tumor development later in life. Since the reports about beneficial effects of soy against cancer come primarily from Asian populations who have consumed soy foods since childhood and whose diet and lifestyle differs in many other ways from Western countries, the expectations of individuals in Western countries who start eating soy products later in life may not be fulfilled. Therefore, future research in different populations should focus on how soy affects cancer risk throughout life.