Risk Of Advanced Prostate Cancer Research Articles

Appendectomy and risk of prostate cancer in the Health Professionals Follow-up Study.

Appendectomy is a common surgical procedure to treat appendicitis. Limited studies examined its association on prostate cancer, with one large cohort study suggesting significant increased risk of overall and advanced prostate cancer, especially among younger men. A total of 49,104 men in the Health Professionals Follow-up Study were followed from 1986 to 2016. Cox proportional hazards models were applied to evaluate the association between self-reported history of appendectomy and risk of overall and subtype specific prostate cancer, adjusted for multiple risk factors. During 30 years of follow-up, we documented 7,253 overall prostate cancer including 579 advanced and 1,092 lethal events. Compared to men without appendectomy, those who reported at baseline having had appendectomy were not at higher risk of overall (hazard ratio (HR)=1.01, 95% CI = 0.95 to 1.07), advanced (HR=0.99, 95% CI = 0.81 to 1.23) or lethal (HR=1.04, 95% CI = 0.89 to 1.20) prostate cancer. The association remained null when stratified by age. We found no evidence of an association between appendectomy and risk of overall and clinically important prostate cancer. We showed that appendectomy was not associated with overall or advanced prostate cancer adjusted for multiple risk factors among a large population of men with 30 years of follow-up.

Abstract 2203: Dietary patterns and prostate cancer risk in the Multiethnic Cohort Study

Abstract Background: A growing body of research has shown the benefits of a healthy diet on a variety of cancer outcomes. Evidence is inconsistent for prostate cancer and research in diverse populations is limited. Methods: In the Multiethnic Cohort Study (MEC), we conducted a prospective cohort analysis to investigate the association of four diet quality indices (DQIs; AHEI-2010, aMED, HEI-2015, DASH; a higher score indicates healthier diet), three plant-based diet indices (PDI, hPDI, uPDI), two inflammatory (DII, EDIP), and two insulinemic dietary indices (EDIH, EDIR) (a higher score indicates more pro-inflammatory or pro-insulinemic diet) with incidence of prostate cancer (PCa) in 79,930 men from five racial/ethnic groups (White, African American, Japanese American, Latino, and Native Hawaiian). All dietary scores were constructed from a baseline quantitative food frequency questionnaire. Outcomes examined included total PCa, high-grade PCa (Gleason score > 7), advanced PCa (regional or distant), aggressive PCa (high-grade or advanced), and lethal PCa (distant or death due to PCa). Hazard ratios (HR) and 95% confidence intervals (CI) per one standard deviation (SD) increase in the dietary score were estimated from Cox proportional hazards models, overall and by race/ethnicity. Associations were considered nominally significant at P < 0.05. Results: During a mean follow-up of 18.9 years, a total of 9,759 incident PCa cases were identified, including 2,503 high-grade, 1,706 advanced, 3,430 aggressive, and 1,426 lethal PCa cases. None of the dietary scores was significantly associated with total PCa. We found a significant association between DII and advanced PCa (HR=1.08, 95% CI=1.01-1.15) overall and the association appeared to be the strongest in African Americans (HR=1.17, 95% CI=1.00-1.36) and Native Hawaiians (HR=1.29, 95% CI=0.98-1.68). We also observed weak associations of the four DQIs with advanced PCa (HR of 0.95-0.96, P of 0.07-0.10) in the overall population, among which a higher DASH score was significantly associated with a 15% (95% CI = 0.75-0.96) lower risk of advanced PCa in African Americans. In addition, we observed that several inflammatory (EDIP) and insulinemic (EDIH, EDIR) dietary scores were associated with lower incidence of advanced, aggressive, or lethal PCa (HR=0.89-0.95, P of 0.03-0.05), which requires further investigation. Conclusions: Our findings suggest that diets with high proinflammatory potential may increase risk of advanced PCa while following a healthy dietary pattern may reduce the risk of advanced PCa. Further studies are needed to better understand the inconsistent results across studies on diet and PCa risk and whether our findings can be replicated in other populations. Citation Format: Wei Xiong, Song-Yi Park, Anqi Wang, Peggy Wan, Lynne R. Wilkens, Loïc Le Marchand, Christopher A. Haiman, Fei Chen. Dietary patterns and prostate cancer risk in the Multiethnic Cohort Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2203.

Abstract 2207: Fiber intake and risk of lethal prostate cancer among men at increased genetic risk

Abstract Introduction High fiber intake from grains may lower advanced prostate cancer risk by enhancing insulin sensitivity, lowering insulin-like growth factor 1 and systemic inflammation. Whether a high-fiber diet can lower risk of metastatic disease and prostate cancer death in men at high genetic risk is unclear. Methods Using a new 400-SNP polygenic risk score (PRS) for prostate cancer, we quantified the genetic risk of 10,269 men with available genotype data in the Health Professionals Follow-up Study, followed between 1993 and 2019. Men in the top 50-100% PRS category were considered high-risk and included for analysis. Total fiber intake and different sources (cereal, fruits, vegetables) were assessed by validated food frequency questionnaires. Overall and lethal prostate cancer (metastatic disease/prostate cancer death) were analyzed using Cox proportional hazards models estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Results During 26 years of follow-up, we recorded 1,494 overall and 174 lethal prostate cancer events in the high genetic risk group. As expected, no associations were observed fiber intake with risk of overall prostate cancer. For lethal prostate cancer, the results varied according to the source of fiber. Higher cereal fiber intake was associated with a lower risk of lethal prostate cancer (per 3 g/d higher intake: 0.81 [0.68, 0.97], P-trend=0.02). We further observed a higher disease risk among men with higher fruit fiber intake (per 3g/d higher intake: 1.18 [1.02, 1.36], P-trend=0.03). The associations remained similar when mutually adjusted for each fiber type. No associations were observed for total or vegetable fiber intake. Conclusion In this analysis of men at high prostate cancer genetic risk, we observed that higher cereal fiber intake was associated with lower lethal prostate cancer risk, whereas higher fruit fiber intake showed an opposite trend. Further studies in different populations and investigations into the underlying mechanisms are needed. Fiber intake with risk of overall and lethal prostate cancer among men at high genetic risk. Fiber type Overall prostate cancer: No.event/PY Overall prostate cancer: HR (95% CI) Lethal prostate cancer: No.event/PY Lethal prostate cancer: HR (95% CI) All fiber, g/d T1, median=15.8 490/66047 ref. 42/73826 ref. T2, median=21.8 484/62237 0.96 (0.83-1.11) 61/69849 1.16 (0.77-1.75) T3, median=29.9 520/67374 1.02 (0.86-1.21) 71/75242 1.24 (0.75-2.05) Per 3 g/d 0.98 (0.96-1.01) 1.00 (0.92-1.08) P for trend 0.27 0.93 Cereal fiber, g/d T1, median=4.6 491/63911 ref. 49/72367 ref. T2, median=6.7 512/66251 1.04 (0.91-1.20) 76/73384 1.30 (0.90-1.87) T3, median=9.4 491/65496 0.92 (0.80-1.06) 49/73166 0.75 (0.50-1.12) Per 3 g/d 0.96 (0.90-1.01) 0.81 (0.68-0.97) P for trend 0.14 0.02 Fruit fiber, g/d T1, median=2.5 471/66306 ref. 33/74056 ref. T2, median=4.5 514/63268 1.06 (0.92-1.22) 51/70430 1.21 (0.76-1.91) T3, median=7.2 509/66085 1.00 (0.86-1.16) 90/74431 1.84 (1.18-2.87) Per 3 g/d 0.97 (0.91-1.03) 1.18 (1.02-1.36) P for trend 0.34 0.03 Vegetable fiber, g/d T1, median=4.8 481/64139 ref. 51/71594 ref. T2, median=6.9 505/64938 1.04 (0.91-1.20) 66/72291 1.22 (0.84-1.78) T3, median=9.6 508/66581 1.04 (0.90-1.20) 57/75031 0.98 (0.65-1.45) Per 3 g/d 0.99 (0.93-1.05) 0.97 (0.82-1.15) P for trend 0.72 0.74 Citation Format: Yiwen Zhang, Konrad H. Stopsack, Lorelei A. Mucci, Edward Giovannucci, Anna Plym. Fiber intake and risk of lethal prostate cancer among men at increased genetic risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2207.

Biological and clinical significance of the AGE-RAGE axis in the aggressiveness and prognosis of prostate cancer.

Dietary factors and chronic hyperglycemia are linked to the formation of advanced glycation end products (AGEs) and prostate cancer (PCa) risk. The activation of the receptor for AGEs (RAGE) acts as a bridge between various RAGE ligands and certain malignancies. This study showed that the interaction of AGEs and RAGE promoted PCa cell proliferation, invasion, and autophagy-mediated survival in response to chemotherapeutic agents. RAGE-overexpressed PCa cells underwent epithelial-mesenchymal transition and showed increased cancer stem cell-like properties. In mouse xenograft models, RAGE-overexpressed cells showed more substantial tumorigenic capacity than parental cells, whereas RAGE knockdown decreased tumorigenicity. The clinical data validated a positive correlation between high AGE and RAGE expressions with poor clinical outcomes. Our findings suggest that the AGE-RAGE axis facilitates PCa progression and aggressiveness. Prostatic AGEs and RAGE expression levels are associated with PCa prognosis. Adherence to a reduced-AGE diet and targeting RAGE are potential approaches to complement and synergize with the current PCa therapies.

Review of Plant-Based Diets and Comprehensive Lifestyle Changes on Prostate Cancer Reversal without the Use of Chemotherapy

Prostate cancer poses a significant health challenge, warranting innovative therapeutic strategies. This review explores the potential of plant-based diets and comprehensive lifestyle modifications as a non-chemotherapy approach to prostate cancer reversal. While chemotherapy is the conventional treatment for advanced prostate cancer, the adverse effects it entails have driven the exploration of alternative, less invasive interventions. The analysis considers a wide range of research, including interventional and observational studies, revealing the positive impact of plant-based diets on short-term oncologic outcomes, general health, and nutrition. Lifestyle interventions significantly reduced the need for conventional treatments, demonstrating the potential for delaying or avoiding them altogether. Furthermore, adopting plant- based diets exhibited a notable association with lower risks of advanced and fatal prostate cancer. Although direct evidence on prostate cancer reversal without chemotherapy remains limited, the reviewed studies underscore the importance of dietary and lifestyle adjustments in mitigating prostate cancer risks and enhancing overall outcomes. Further research is needed to explore the long-term implications of whole-food plant-based diets and to develop targeted interventions for prostate cancer prevention and treatment without chemotherapy

Chronic Glucocorticoid Use and Risk for Advanced Prostate Cancer at Presentation: A SEER-Medicare Cohort Study

BackgroundExamine the relationship between exposure to systemic glucocorticoids (steroids) and advanced prostate cancer (PCa) at presentation. Prior work suggested that steroid use may be associated with increased PCa risk. Materials and MethodsWe queried the linked SEER-Medicare database (2004-2015) to identify PSA screened patients diagnosed with PCa. Criteria for screening included a PSA lab test or DRE exam in both the 12 month and 13 to 36 month periods prior to diagnosis of PCa. Steroid exposure was determined using Medicare Part D and groups were divided based on duration of use in the 3 years prior to diagnosis: controls with no exposure, <30 days, 30 days – 1 year, 1 to 2 years, and >2+ years. Advanced PCa was defined as systemic metastases or regional lymph node metastasis at presentation. Risk estimates for advanced PCa at presentation for steroid exposure groups vs. controls were assessed with univariable and multivariable logistic regression models. ResultsWe identified 22,920 PSA screened patients diagnosed with PCa of which 29% used glucocorticoids in the exposure period. The mean (SD) duration for glucocorticoid use (in days) among all steroid users was 76.7 days (192.1). On univariable and multivariable analyses, > 2 years of steroid exposure was associated with significantly increased risk for advanced PCa (OR 2.06, 95% CI 1.35-3.14 and OR 1.74, 95% CI 1.12-2.69, respectively). ConclusionIn this population-based PSA-screened cohort, prolonged steroid use was associated with increased risk of advanced PCa at diagnosis. With the widespread use of glucocorticoids, it is important to consider the role steroids may play in PCa pathogenesis.

Impact of modifiable lifestyle risk factors for prostate cancer prevention: a review of the literature.

Although prostate cancer (PCa) is one of the most common cancers among men, the impact of modifiable risk and protective factors is still being debated. This review aims to qualitatively summarize the most recent studies related to potential healthy lifestyle factors affecting the development of PCa. The literature focusing on modifiable risk factors for prostate cancer was reviewed. Medline and Embase via the Ovid database were searched, and all relevant and inherent articles were analyzed. Non-eligible publications, such as review articles, editorials, comments, guidelines, or case reports, were excluded. This review confirms that there is strong evidence that being overweight or obese increases the risk of advanced prostate cancer (assessed by body mass index (BMI), waist circumference, and waist-hip ratio), particularly considering central adiposity and ethnicity as contributing factors. The possible contribution of smoking still seems not entirely clear, while alcohol seems to affect PCa prevention in patients taking 5α-reductase inhibitors (5-ARIs). Dietary fibers may have anti-inflammatory properties and improve insulin sensitivity by reducing IGF bioactivity. In particular, dietary fiber intake like insoluble and legume fibers may be inversely associated with prostate cancer risk. Also, hyperglycemia and hyperinsulinemia, with untreated diabetic fasting blood glucose levels, could be modifiable prostate cancer risk factors. In two studies, aspirin was associated with a lower risk of lethal PCa and overall mortality. Concerning the role of vitamins, despite conflicting and divergent results, serum retinol concentration seems to be associated with an increased risk of prostate cancer and high-grade prostate cancer. Some studies resulted in disagreement about the role of selenium and vitamin E. We found inconsistent and controversial findings about the association between vitamin D and prostate cancer risk. Far from being conclusive evidence, our findings confirm some strong evidence already found in the previous literature and highlight the need to clarify the role of some risk factors whose role is not yet completely known. This effort would facilitate the cultural and social change that may allow the shift from the treatment of prostate cancer when diagnosed to the real efforts needed for systematic prevention.

Association between nut consumption and prostate cancer risk in adults: A systematic review and dose-response meta-analysis of observational studies

AimsData on the association between nut consumption and prostate cancer risk are conflicting. Therefore, this systematic review and dose-response meta-analysis aimed to summarize available findings from observational studies on the associations of nut intake with risk of total, advanced, non-advanced, and fatal prostate cancers. Data synthesisWe searched the online databases of PubMed, Scopus, and Web of Science as well as Google Scholar using appropriate keywords to identify eligible articles up to September 2022. In total, 11 articles with a total sample size of 287,786 participants and 32,213 cases of prostate cancer were included in the current systematic review and meta-analysis. By comparing the highest and lowest intake of total nuts, pooled relative risks (RRs) and 95% confidence intervals (95% CIs) for total, advanced, non-advanced, and fatal prostate cancers were 0.94 (95% CI: 0.85–1.04, P = 0.22), 1.10 (95% CI: 0.98–1.24, P = 0.12), 0.97 (95% CI: 0.85–1.11, P = 0.69), 0.97 (95% CI: 0.79–1.18, P = 0.73), respectively, which indicated non-significant inverse associations for total, non-advanced, and fatal prostate cancers and a non-significant positive association for advanced prostate cancer. In the dose-response analyses, we found no evidence of a linear or non-linear association between total nut intake and prostate cancer risk. Data on other types of nuts, including walnut, tree nuts, peanut, and peanut butter, were not sufficient for performing a meta-analysis. ConclusionWe found no significant association between nut intake and risk of total, advanced, non-advanced, and fatal prostate cancer. Further studies are required to confirm our findings. Prospero registration codeCRD42022347094. Ethical approvalNot required.

Characterizing the Role of Calcium Sensing Receptor in the Progression of Obesity-Mediated Aggressive Prostate Cancer Phenotype

Obesity increases the risk of advanced prostate cancer (PCa). The calcium sensing receptor (CaSR) has been shown to be responsive to obesity-mediated cytokines and is upregulated in metastatic PCa. This study used a novel in vitro approach, involving the exposure of PCa cells to sera, from obese or normal weight males, and to CaSR inhibitor NPS-2143. Cell viability was determined using MTT assay. MMP-9 activity and invasion were assessed using zymography and invasion chambers, respectively. Microscopy was used to visualize EMT proteins. qRT-PCR and immunoblot analysis were used to quantify changes in genes and proteins important for tumorigenesis. Exposure to obese sera increased the proliferation, and the invasive capacity of PCa cells and de-localized epithelial-mesenchymal transition markers, which were attenuated with CaSR inhibition. Exposure to obese sera upregulated mRNA expression of PTHrP and protein expression of COX-2, IL-6, and CaSR. Inhibition of CaSR downregulated the mRNA expression of PTHrP and RANK, and protein expression of pERK and TNF-α. Obesity was shown to increase invasion and upregulate the expression of genes and proteins involved in PCa tumorigenesis. CaSR inhibition downregulated the expression of several of these factors. Thus, CaSR is a potentially important protein to target in obesity-mediated PCa progression.

Statins and prostate cancer-hype or hope? The biological perspective.

Growing evidence suggests that men prescribed a statin for cholesterol control have a lower risk of advanced prostate cancer (PCa) and improved treatment outcomes; however, the mechanism by which statins elicit their anti-neoplastic effects is not well understood and is likely multifaceted. Statins are potent and specific inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the rate-limiting enzyme of the mevalonate (MVA) metabolic pathway. This two-part series is a review of the observational and experimental data on statins as anti-cancer agents in PCa. In this article, we describe the functional role that deregulated MVA metabolism plays in PCa progression and summarize the biological evidence and rationale for targeting the MVA pathway, with statins and other agents, for the treatment of PCa.

Abstract 2270: Hyperlipidemia promotes aggressive variant prostate cancer via RNA-binding protein Quaking

Abstract Introduction: Hyperlipidemia has been associated with increased risk of advanced stage and high Gleason grade prostate cancer (PCa), yet the underlying mechanism is not completely understood. Quaking (QKI) is an RNA-binding protein (RBP) that regulate lipid metabolism. For PCa, QKI overexpression has been associated with increased chance of metastatic recurrence. Method: We performed RNA sequencing of prostate cancer tissues of hyperlipidemia (n = 12) and normolipidemia (n=32). Tissue samples were acquired by MRI-US fusion targeted biopsy. DESeq2 and GSEA was used to identify differently expressed genes and enriched genesets. A web-based RBP motif screening tool TRANSITE was utilized to identify active RBPs in hyperlipidemia-associated PCa. Results: PCa samples of hyperlipidemia patients exhibited poorer histology than normolipidemia PCA. RNA sequencing found that hyperlipidemia-associated PCa is enriched of Myc-regulated genes as well as interferon or innate immunity-associated genes. Interestingly, hyperlipidemia-associated PCa gene expression signature identified PCa samples devoid of common PCa genetic alterations - TMPRSS2-ERG fusion and PTEN deletion/mutation. RBP motif screening found QKI as one of the top enriched RBP in hyperlipidemia-associated PCa transcriptome. In a separate a consecutive radical prostatectomy series (n=190), we found that QKI-high (immunohistochemistry staining score 2-3) tumors had significantly higher serum cholesterol than QKI-low (score 0-1) tumors. Overexpression and knockdown experiments proved that QKI is responsible of rapid cell proliferation and interferon-related inflammatory gene expressions, In silico analysis predicted QKI overexpressing cancer cells are susceptive to stain-mediated ferroptosis-like cell death. Mechanistically, QKI regulates expression of acyl-CoA synthetase long-chain family member 4 (ACSL4), which dictates the sensitivity of QKI overexpressing cells to ferroptosis. Conclusion: Hyperlipidemia was associated with aggressive pathologic characteristics of PCa without TMPRSS2-ERG fusion or PTEN deletion/mutation, and high tissue expression of QKI, an RNA-binding protein. QKI overexpression in PCa increased sensitivity to ACSL4-mediated ferroptosis by statins. This explains the epidemiological associations between hyperlipidemia and PCa, and will guide molecular subtype-driven drug repurposing studies. Citation Format: Hyun Ho Han, Jin Sol Sung, Dong Wook Song, Cheol Keun Park, Nam Hoon Cho, Young Deuk Choi, Woo Jin Ko. Hyperlipidemia promotes aggressive variant prostate cancer via RNA-binding protein Quaking [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2270.

Regular, Long-Duration Multivitamin Use and Risk of Overall and Aggressive Prostate Cancer in the Health Professionals Follow-Up Study.

Multivitamin supplement is commonly used among older adults in the United States. Evidence on multivitamin use and prostate cancer risk is limited, and some suggested potential risk for clinically important subtypes of cancer. A total of 48,137 men from the Health Professionals Follow-up Study were followed from 1986 to 2017. Multivitamin use and frequency were self-reported at baseline and updated biennially. Clinical features of prostate cancer included advanced, lethal and high-grade outcomes. Cox proportional hazards models were used to estimate multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) of multivitamin use and incidence of prostate cancer. The median followup for men without prostate cancer diagnosis or death was 30.7 years. We documented 7,108 incident prostate cancer cases including 564 advanced and 1,065 lethal. Overall, we observed a null association between multivitamin use and risk of prostate cancer. Compared to never-users, men who used multivitamin 10 or more tablets per week had similar risk of advanced (HR: 1.14, 95% CI: 0.77-1.70, Ptrend=0.46) or lethal (HR: 1.07, 95% CI: 0.80-1.44, Ptrend=0.59) prostate cancer, and multivitamin use of 15 years or more was not associated with risk of advanced (HR: 1.10, 95% CI: 0.80-1.50, Ptrend=0.46) or lethal (HR: 1.04, 95% CI: 0.83-1.31, Ptrend=0.13) prostate cancer. Regular or long-duration multivitamin use among older, generally well-nourished men was not associated with either increased or lower risk of overall or aggressive prostate cancer.

Association of plant-based diet index with prostate cancer risk

Plant-based diets are associated with multiple health benefits and a favorable environmental impact. For prostate cancer, previous studies suggest a beneficial role of specific plant-based foods (e.g., tomatoes) and a potentially harmful role of specific animal-based foods (e.g., meat, dairy). However, less is known about plant-based dietary patterns. We sought to examine the relation between plant-based diet indices and prostate cancer risk, including clinically relevant disease. This was a prospective cohort study including 47,239 men in the Health Professionals Follow-Up Study (1986-2014). Overall and healthful plant-based diet indices were calculated from FFQs. Cox proportional hazards models were used to estimate HRs and 95% CIs to examine the risk of incident prostate cancer (total and by clinical category), among men ages <65 and ≥65 y. Of the 47,239 men, 6655 men were diagnosed with prostate cancer over follow-up, including 515 with advanced-stage disease at diagnosis, 956 with lethal disease (metastasis or death), and 806 prostate cancer deaths. Greater overall plant-based consumption was associated with a significantly lower risk of fatal prostate cancer (HR: 0.81; 95% CI: 0.64, 1.01; P-trend = 0.04). In men aged <65, a higher plant-based diet index was associated with a lower risk of advanced, lethal, and fatal prostate cancer. Moreover, greater consumption of a healthful plant-based diet was associated with lower risks of total (HR: 0.84; 95% CI: 0.73, 0.98; P-trend = 0.046) and lethal prostate cancer (HR: 0.56; 95% CI: 0.34, 0.94; P-trend = 0.03) at age <65. There were no associations between overall or healthful plant-based diet indices with prostate cancer among men ≥65 y. Fewer than 1% of participants followed a strict vegetarian or vegan diet. This prospective study provides supportive evidence that greater consumption of healthful plant-based foods is associated with a lower risk of aggressive forms of prostate cancer, with stronger benefit among men aged <65 y.

A Rare Germline HOXB13 Variant Contributes to Risk of Prostate Cancer in Men of African Ancestry

A rare African ancestry–specific germline deletion variant in HOXB13 (X285K, rs77179853) was recently reported in Martinican men with early-onset prostate cancer. Given the role of HOXB13 germline variation in prostate cancer, we investigated the association between HOXB13 X285K and prostate cancer risk in a large sample of 22 361 African ancestry men, including 11 688 prostate cancer cases. The risk allele was present only in men of West African ancestry, with an allele frequency in men that ranged from 0.40% in Ghana and 0.31% in Nigeria to 0% in Uganda and South Africa, with a range of frequencies in men with admixed African ancestry from North America and Europe (0–0.26%). HOXB13 X285K was associated with 2.4-fold increased odds of prostate cancer (95% confidence interval [CI] = 1.5-3.9, p = 2 × 10−4), with greater risk observed for more aggressive and advanced disease (Gleason ≥8: odds ratio [OR] = 4.7, 95% CI = 2.3–9.5, p = 2 × 10−5; stage T3/T4: OR = 4.5, 95% CI = 2.0–10.0, p = 2 × 10−4; metastatic disease: OR = 5.1, 95% CI = 1.9–13.7, p = 0.001). We estimated that the allele arose in West Africa 1500–4600 yr ago. Further analysis is needed to understand how the HOXB13 X285K variant impacts the HOXB13 protein and function in the prostate. Understanding who carries this mutation may inform prostate cancer screening in men of West African ancestry. Patient summaryA rare African ancestry–specific germline deletion in HOXB13, found only in men of West African ancestry, was reported to be associated with an increased risk of overall and advanced prostate cancer. Understanding who carries this mutation may help inform screening for prostate cancer in men of West African ancestry.

A Review on Role of Circadian Rhythms in Management of Prostate Cancer

The circadian clock is a molecular evolutionary mechanism that controls the time of physiology to maintain homeostasis. Circadian disorder in particular has been identified as an independent risk factor for cancer and has been classified as a carcinogen. The circadian rhythm regulates several biological pathways, including oncogenic tumors, metabolism, and cell reproduction. The new data examined in this article suggest that circadian regulatory functions play a key role in various aspects of cancer, including cell proliferation control, cell death, DNA repair, and metabolism. Circadian irregularities are incorrect input signals, such as exposure to night light, variability in circadian rhythm genes, and output changes that regulate circadian behavior, including melatonin. Night work, shift work, workday changes, urinary melatonin levels, and insomnia put older men at risk for prostate cancer. Melatonin has anti-cancer properties. Men with lower melatonin levels in the morning had a higher risk of advanced or fatal prostate cancer. Melatonin, a hormone found in the pineal gland, plays an important role in the functioning of the circadian function. The integration of circadian biology into cancer research opens up new avenues for more effective cancer treatment, including the prevention, diagnosis, and treatment of this destructive disease. This review examines the role of the circadian clock in tumor formation and cancer symptoms, and examines whether pharmacological changes in circadian clock genes may lead to new treatment options.

Adolescent Plant Product Intake in Relation to Later Prostate Cancer Risk and Mortality in the NIH-AARP Diet and Health Study

BackgroundAlthough fruit and vegetable intake during adolescence, a potentially sensitive time period for prostate cancer (PCa) development, has been proposed to protect against PCa risk, few studies have investigated the role of adolescent plant product intake in PCa development. MethodsIntake of various vegetables, fruit, and grains by males at ages 12–13 y was examined in relation to later PCa risk and mortality in the NIH-AARP Diet and Health Study. Cox proportional hazards regression was used to calculate HRs and 95% CIs of nonadvanced (n = 14,238) and advanced (n = 2,170) PCa incidence and PCa mortality (n = 760) during 1,729,896 person-years of follow-up. ResultsNone of the plant products examined were associated consistently with all PCa outcomes. However, greater adolescent intakes of tomatoes (P-trend = 0.004) and nonstarch vegetables (P-trend = 0.025) were associated with reduced risk of nonadvanced PCa, and greater intakes of broccoli (P-trend = 0.050) and fruit juice (P-trend = 0.019–0.025) were associated with reduced risk of advanced PCa and/or PCa mortality. Positive trends were also observed for greater intakes of fruit juice (P-trend = 0.002), total fruit (P-trend = 0.014), and dark bread (P-trend = 0.035) with nonadvanced PCa risk and for greater intakes of legumes (P-trend < 0.001), fiber (P-trend = 0.001), and vegetable protein (P-trend = 0.013–0.040) with advanced PCa risk or PCa mortality. ConclusionsOur findings do not provide strong evidence to suggest that adolescent plant product intake is associated with reduced PCa risk.

Effect of Statins on the Risk of Different Stages of Prostate Cancer: A Meta-Analysis

Introduction: The aim of this article was to investigate the relationship between statins and the risk of different stages or grades of prostate cancer. Methods: A comprehensive literature search was performed for articles published until December 18, 2020, on the PubMed, Embase, and the Cochrane Library databases. The pooled relative risk (RR) and 95% confidence interval (CI) were then analyzed using the STATA.16.0 software. Results: A total of 588,055 patients from 14 studies were included in the analysis. We found that the use of statins expressed a significant correlation with a lower risk of advanced prostate cancer (RR = 0.81, 95% CI: 0.73–0.91; RR = 0.86, 95% CI: 0.75–0.99, respectively). However, no evidence suggested that the use of statins was beneficial for the prevention of localized prostate cancer incidence. Similarly, the pooled results also revealed no association between the use of statins and the risk of high-grade and low-grade prostate cancer. Conclusion: It has been found that the use of statins is associated with a lower risk of advanced prostate cancer but was not related to the risk of localized, low-grade, or high-grade prostate cancer.

MP32-06 ASSOCIATION OF PLANT-BASED DIETARY PATTERNS WITH PROSTATE CANCER RISK

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History II (MP32)1 Sep 2021MP32-06 ASSOCIATION OF PLANT-BASED DIETARY PATTERNS WITH PROSTATE CANCER RISK Stacy Loeb, Benjamin C. Fu, Scott R. Bauer, Claire H. Pernar, June M. Chan, Erin L. Van Blarigan, Edward L. Giovannucci, Stacey A. Kenfield, and Lorelei A. Mucci Stacy LoebStacy Loeb More articles by this author , Benjamin C. FuBenjamin C. Fu More articles by this author , Scott R. BauerScott R. Bauer More articles by this author , Claire H. PernarClaire H. Pernar More articles by this author , June M. ChanJune M. Chan More articles by this author , Erin L. Van BlariganErin L. Van Blarigan More articles by this author , Edward L. GiovannucciEdward L. Giovannucci More articles by this author , Stacey A. KenfieldStacey A. Kenfield More articles by this author , and Lorelei A. MucciLorelei A. Mucci More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002036.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Plant-based diets are associated with multiple health benefits as well as a favorable environmental impact. For prostate cancer, previous studies suggest a beneficial role of specific plant-based foods (e.g., tomatoes with lycopene) and a potentially harmful role of specific animal-based foods (e.g., meat and dairy). However, less is known about plant-based dietary patterns and prostate cancer risk. METHODS: This was a prospective study including 47,243 men followed for up to 28 years in the Health Professionals Follow-up Study. Plant-based dietary indices were calculated using data from food frequency questionnaires collected every four years. Cox proportional hazards models were used to calculate multivariable hazard ratios (HR) and 95% confidence intervals (CI) of the association between plant-based diet in relation to risk of incident prostate cancer. A priori we hypothesized that a plant-based diet would be associated with a lower risk of advanced, lethal and fatal cancers, and among men less than 65 years at diagnosis. RESULTS: A total of 6,660 men were diagnosed with prostate cancer over follow-up, including 516 with advanced stage at diagnosis, 958 with lethal disease and 807 deaths from prostate cancer. There was no association between the overall plant-based dietary index with total prostate cancer risk, although greater overall plant-based consumption was associated with a nonsignificant lower risk of fatal prostate cancer. In men age less than 65 at diagnosis, greater overall consumption of plant-based diet was associated with a lower risk of advanced prostate cancer (HR 0.68, 95% CI 0.42-1.10, p-trend=0.046). Moreover, among younger men, greater consumption of a healthful plant-based diet was associated with lower risks of total prostate cancer (HR 0.81; 95% CI 0.70-0.95, p-trend=0.01) and fatal disease (HR 0.53; 95% CI 0.32-0.90, p-trend=0.03). There were no associations with either the overall or healthful plant-based diet indices with prostate cancer among men older than 65 years. Limitations of the study include that <1% of the participants followed a strict vegetarian or vegan diet. CONCLUSIONS: In addition to well-established benefits for general health and the environment, data from this prospective study provide supportive evidence that greater consumption of healthful plant-based foods may be associated with a lower risk of total and fatal prostate cancer among younger men. Source of Funding: This work was supported by grants from the National Institutes of Health (U01 CA167552, T32 CA009001). SL and LAM are supported by the Prostate Cancer Foundation. SB is supported by grant 1K12DK111028 from the National Institute of Diabetes, Digestive, and Kidney Disorders © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e566-e567 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Stacy Loeb More articles by this author Benjamin C. Fu More articles by this author Scott R. Bauer More articles by this author Claire H. Pernar More articles by this author June M. Chan More articles by this author Erin L. Van Blarigan More articles by this author Edward L. Giovannucci More articles by this author Stacey A. Kenfield More articles by this author Lorelei A. Mucci More articles by this author Expand All Advertisement Loading ...

Definition of Outcome-Based Prostate-Specific Antigen (PSA) Thresholds for Advanced Prostate Cancer Risk Prediction.

Simple SummaryIn this study, we used a well calibrated risk prediction model to define prostate-specific antigen (PSA) thresholds for identifying or excluding advanced prostate cancer (PCa) as an aid to personalize management of the diagnostic workup. PSA concentrations ≤ 4.1 (<65 years old) and ≤3.7 μg/L (≥65 years old) excluded an advanced PCa in patients without glandular inflammation, while PSA > 5.7 (<65) and >6.1 μg/L (≥65) suggested a biopsy referral. In the presence of glandular inflammation, PSA does not provide a valid estimate for risk of advanced cancer since the marker variability is higher and the pre-test probability of PCa is low in this group. The proposed PSA thresholds may allow an individualized approach to the diagnostic workup, assisting patients in making an informed decision. However, patients with asymptomatic prostatitis cannot benefit from the use of this model since they cannot be pre-biopsy identified.We defined prostate-specific antigen (PSA) thresholds from a well calibrated risk prediction model for identifying and excluding advanced prostate cancer (PCa). We retrieved 902 biopsied patients with a pre-biopsy PSA determination (Roche assay). A logistic regression model predictive for PCa including the main effects [i.e., PSA, age, histological evidence of glandular inflammation (GI)] was built after testing the accuracy by calibration plots and Hosmer-Lemeshow test for goodness of fit. PSA thresholds were derived by assuming a diagnostic sensitivity of 95% (rule-out) and 80% (rule-in) for overall and advanced/poorly differentiated PCa. In patients without GI, serum PSA concentrations ≤ 4.1 (<65 years old) and ≤3.7 μg/L (≥65 years old) excluded an advanced PCa (defined as Gleason score ≥ 7 at biopsy), with a negative predictive value of 95.1% [95% confidence interval (CI): 83.0–98.7] and 88.8% (CI: 80.2–93.9), respectively, while PSA > 5.7 (<65) and >6.1 μg/L (≥65) should address biopsy referral. In presence of GI, PSA did not provide a valid estimate for risk of advanced cancer because of its higher variability and the low pre-test probability of PCa. The proposed PSA thresholds may support biopsy decision except for patients with asymptomatic prostatitis who cannot be pre-biopsy identified.

Exploratory assessment of pineal gland volume, composition, and urinary 6-sulfatoxymelatonin levels on prostate cancer risk.

Melatonin levels are partially driven by the parenchyma volume of the pineal gland. Low urinary levels of 6-sulfatoxymelatonin have been associated with increased risk of advanced prostate cancer, but the relationship between pineal gland volume and composition and prostate cancer risk has not been examined. We utilized data from 864 men from the AGES-Reykjavik Study with complete pineal gland volumes and urinary 6-sulfatoxymelatonin measurements. Pineal parenchyma, calcification, and cyst volumes were calculated from brain magnetic resonance imaging. Levels of 6-sulfatoxymelatonin were assayed from prediagnostic urine samples. We calculated Pearson correlation coefficients between parenchyma volume and urinary 6-sulfatoxymelatonin levels. We used Cox proportional hazards regression to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) comparing prostate cancer risk across parenchyma volume tertiles and across categories factoring in parenchyma volume, gland composition, and urinary 6-sulfatoxymelatonin level. Parenchyma volume was moderately correlated with urinary 6-sulfatoxymelatonin level (r = .24; p < .01). There was no statistically significant association between parenchyma volume tertile and prostate cancer risk. Men with high parenchyma volume, pineal cysts and calcifications, and low urinary 6-sulfatoxymelatonin levels had almost twice the risk of total prostate cancer as men with low parenchyma volume, no pineal calcifications or cysts, and low urinary 6-sulfatoxymelatonin levels (HR: 1.98; 95% CI: 1.02, 3.84; p: .04). Although parenchyma volume is not associated with prostate cancer risk, pineal gland composition and other circadian dynamics may influence risk for prostate cancer. Additional studies are needed to examine the interplay of pineal gland volume, composition, and melatonin levels on prostate cancer risk.