Risk Of Developing Prostate Cancer Research Articles

Homologous recombination repair gene mutations in Malaysian prostate cancer patients.

Genetic alterations in the homologous recombination repair (HRR) genes are associated with an increased risk of prostate cancer development, and patients harboring these mutations can benefit from targeted therapy. The main aim of this study is to identify genetic alterations in HRR genes as a potential target for targeted treatment. In this study, targeted next generation sequencing (NGS) is used to analyze mutations in the protein-coding regions of the 27 genes involved in HRR and mutations in hotspots of 5 cancer-associated genes in four FFPE samples and three blood samples from prostate cancer patients. We identified two mutations in TP53 and KRAS. We also identified four conflicting interpretations of pathogenicity variants in BRCA2, STK11 genes and one variant of uncertain significance in the RAD51B gene. In addition, we detected one drug response variant in TP53, and two novel variants in CDK12 and ATM. Our results revealed some actionable pathogenic and potential pathogenic variants that may be associated with response to the Poly (ADP-ribose) polymerase (PARP) inhibitor treatment. More studies in a larger cohort are needed to evaluate and determine the association of HRR mutations with prostate cancer.

<i>BRCA</i> associated prostate cancer. <i>BRCA</i> heredity of one family

In western European countries prostate cancer is one of the most common malignant disease among male population. Due to innovations in molecular genetics research technology over recent years genetic features of etiology and pathogenesis of prostate cancer have been discovered and this helped to distinguish people with high risk of prostate cancer development. Hereditary forms of malignant tumors occupy a special position due to association with mutations in BRCA1/2 gene in a group of patients with prostate cancer. The most important part of examination of patients with malignant diseases is medico-genetic counseling. It helps to reveal the hereditary of the disease. The detection of germinal mutations in BRCA1/2 gene helps to personify diagnostic measures for primary prophylaxis and treatment of prostate cancer.Here is a case of one patient with hereditary feature of prostate cancer with a mutation in BRCA1 gene. It is important to note that revealing mutations in BRSA gene helps to early diagnose malignant neoplasms. Screening measures to reveal germinal mutations in healthy population can improve early detection of such malignant diseases as breast cancer, prostate cancer and other malignant neoplasms.

Risk of prostate cancer in patients with inflammatory bowel disease: a nationwide cohort study in South Korea.

Several studies have suggested an association between inflammatory bowel disease (IBD) and the risk of prostate cancer development. However, these findings are inconsistent, and studies based on Asian populations are limited. We compared the risk of prostate cancer according to IBD status using the Korean National Health Insurance Service database. A population-based retrospective cohort of age-matched 59,044 non-IBD patients and 14,761 IBD patients between January 2009 and December 2011 was analyzed up to December 2017. The risk of prostate cancer was compared between patients with IBD and controls using the Cox proportional hazards regression model and Kaplan-Meier survival analysis. During a median follow-up of 6 years, the incidence rate of prostate cancer was 264 per 100,000 person-years in non-IBD patients and 242 per 100,000 person-years in patients with IBD. IBD status was not associated with the risk of prostate cancer compared to non-IBD [adjusted hazard ratio (aHR) 0.93, 95% confidence interval (CI): 0.80-1.08, p = 0.32). The cumulative incidence of prostate cancer did not differ by IBD status (non-IBD patients versus IBD patients: log-rank p = 0.27; non-IBD patients versus ulcerative colitis versus Crohn's disease: log-rank p = 0.42). In multivariate analysis, age was an independent risk factor for the development of prostate cancer (HR 1.03, 95% CI: 1.02-1.03, p < 0.001). In our population-based study, IBD status was not associated with the risk of prostate cancer.

Role of Genetic Variations in CDK2, CCNE1 and p27KIP1 in Prostate Cancer.

Our aim was to investigate possible influences of genetic variants in genes involved in the G1/S transition [cyclin-dependent kinase-2 (CDK2), cyclin E1 (CCNE1) and cyclin-dependent kinase inhibitor 1B (p27KIP1)] on the expression/activity of their corresponding proteins and to assess the functional impact of these variants on the risk of prostate cancer. We genotyped 530 cases and 562 healthy controls for two relevant single nucleotide polymorphisms (CDK2 rs2069408 and CCNE1 rs997669) by TaqMan genotyping assay. p27KIP1 rs2066827 polymorphisms were studied by polymerase chain reaction-restriction fragment length polymorphism assay. In addition, the expression of CDK2, CCNE1 and p27KIP1 was evaluated by quantitative real-time-polymerase chain reaction and western blotting in 44 prostate cancer tissues and 31 benign prostatic hyperplasia tissues. No association was found between CDK2 rs2069408, CCNE1 rs997669 or p27KIP1 rs2066827 polymorphisms and an increased risk of prostate cancer development. Higher CDK2 expression was more prevalent in those with rs2069408 GG genotype than in AA carriers (p>0.05). We also noted reduced p27KIP1 protein expression in those with the p27KIP1 G109 allele. No difference was observed for CCNE1 expression in relation to the risky genotype (CC). A significant association was detected between CCNE1 mRNA overexpression and development of higher-grade carcinomas (Gleason score >7, p<0.05). Polymorphisms CDK2 rs2069408, CCNE1 rs997669 and p27KIP1 rs2066827 have no significant impact on prostate cancer risk nor on the gene and protein expression of CDK2, CCNE1 and p27KIP1, although high CCNE1 expression was significantly associated with a higher tumour grade in patients with prostate cancer.

The BARCODE1 Pilot: a feasibility study of using germline single nucleotide polymorphisms to target prostate cancer screening.

ObjectivesTo assess the feasibility and uptake of a community‐based prostate cancer (PCa) screening programme selecting men according to their genetic risk of PCa. To assess the uptake of PCa screening investigations by men invited for screening. The uptake of the pilot study would guide the opening of the larger BARCODE1 study recruiting 5000 men.Subjects and MethodsHealthy males aged 55–69 years were invited to participate via their general practitioners (GPs). Saliva samples were collected via mailed collection kits. After DNA extraction, genotyping was conducted using a study specific assay. Genetic risk was based on genotyping 130 germline PCa risk single nucleotide polymorphisms (SNPs). A polygenic risk score (PRS) was calculated for each participant using the sum of weighted alleles for 130 SNPs. Study participants with a PRS lying above the 90th centile value were invited for PCa screening by prostate magnetic resonance imaging (MRI) and biopsy.ResultsInvitation letters were sent to 1434 men. The overall study uptake was 26% (375/1436) and 87% of responders were eligible for study entry. DNA genotyping data were available for 297 men and 25 were invited for screening. After exclusions due to medical comorbidity/invitations declined, 18 of 25 men (72%) underwent MRI and biopsy of the prostate. There were seven diagnoses of PCa (38.9%). All cancers were low‐risk and were managed with active surveillance.ConclusionThe BARCODE1 Pilot has shown this community study in the UK to be feasible, with an overall uptake of 26%. The main BARCODE1 study is now open and will recruit 5000 men. The results of BARCODE1 will be important in defining the role of genetic profiling in targeted PCa population screening. Patient SummaryWhat is the paper about?Very few prostate cancer screening programmes currently exist anywhere in the world. Our pilot study investigated if men in the UK would find it acceptable to have a genetic test based on a saliva sample to examine their risk of prostate cancer development. This test would guide whether men are offered prostate cancer screening tests.What does it mean for patients?We found that the study design was acceptable: 26% of men invited to take part agreed to have the test. The majority of men who were found to have an increased genetic risk of prostate cancer underwent further tests offered (prostate MRI scan and biopsy). We have now expanded the study to enrol 5000 men. The BARCODE1 study will be important in examining whether this approach could be used for large‐scale population prostate cancer screening.

Impact of early hypothalamic-pituitary-gonadal axis maturation on prostate cancer: cross-sectional analysis of a Veterans affairs cohort.

BackgroundIt has been hypothesized that earlier onset of puberty, and thus a more prolonged exposure to high androgen levels, increases risk of prostate cancer development. Our objective was to determine whether earlier age of first shave and height, as surrogates of pubertal onset, were associated with risk of prostate cancer diagnosis.MethodsA prospectively collected outcomes registry of patients presenting for a prostate biopsy at the Charlie Norwood Veterans Affair Medical Center in Augusta, GA between July 1995 and June 2016 was utilized. The associations between age of first shave and height, each, and risks of a positive prostate biopsy, high grade cancer, and high volume disease were evaluated using univariable and multivariable logistic regression analysis, controlling for baseline patient demographic and oncologic characteristics.ResultsOur cohort included 2,456 patients. Biopsies were positive in 1,257 (51.2%) patients, of whom 293 (23.3%) and 407 (32.4%) had high grade and volume disease, respectively. Median age of first shave was 17.0 years (interquartile range 16.0–19.0) and height was 177.7 cm (172.8–182.9). On multivariable analysis, later of age of first shave was significantly associated with increased odds of a positive prostate biopsy (odds ratio for >18 versus <16 years: 5.34, P=0.02) and taller patients had significantly increased odds of high grade cancer (odds ratio for 175–180 versus <175 cm: 7.46, P=0.037).ConclusionsAmongst patients presenting for a prostate biopsy, those with a later age of first shave and taller height have an increased risk of a positive prostate biopsy and high grade prostate cancer, respectively.

Interleukin-13 rs1800925/-1112C/T promoter single nucleotide polymorphism variant linked to anti-schistosomiasis in adult males in Murehwa District, Zimbabwe.

Chronic schistosomiasis is predominantly induced through up-regulation of inflammatory cytokines such as interleukin (IL)-13. IL-13 may contribute to the disease outcomes by increasing eosinophil infiltration thereby promoting fibrosis. IL-13 may act as an immunosuppressive inflammatory cytokine that may promote carcinogenesis and also may offer protection against schistosomiasis thereby reducing risk of schistosome infections. Our study evaluated the frequency of the IL-13 rs1800925/-1112 C/ T promoter single nucleotide polymorphisms (SNPs) among schistosomiasis infected individuals and assessed the association of the variants on IL-13 cytokine levels. We also investigated IL-13 rs1800925 polymorphisms on prostate-specific antigen levels as an indicator for risk of prostate cancer development. The study was cross-sectional and included 50 schistosomiasis infected and 316 uninfected male participants residing in Murehwa District, Zimbabwe. IL-13 rs1800925 SNPs were genotyped by allele amplification refractory mutation system-polymerase chain reaction. Concentrations of serum prostate-specific antigens and plasma IL-13 were measured using enzyme-linked immunosorbent assay. Frequencies of the genotypes CC, CT and TT, were 20%, 58% and 22% in schistosomiasis infected, and 18.3%, 62.1% and 19.6% in uninfected participants with no statistical differences. There were significantly (p<0.05) higher IL-13 cytokine levels among both infected and uninfected participants with the genotypes CC and CT; median 92.25 pg/mL and 106.5 pg/mL, respectively, compared to TT variant individuals; 44.78 pg/mL. Within the schistosomiasis uninfected group, CC and CT variants had significantly (p<0.05) higher IL-13 levels; median 135.0 pg/mL and 113.6 pg/mL, respectively compared to TT variant individuals; 47.15 pg/mL. Within the schistosomiasis infected group, CC, CT and TT variant individuals had insignificant differences of IL-13 level. Using logistic regression, no association was observed between prostate-specific antigen levels, IL-13 cytokine levels and IL-13 rs1800925 variants (p>0.05). IL-13 rs1800925 C variant individuals had the highest IL-13 cytokine levels among the schistosomiasis uninfected suggesting that they may be protective against Schistosoma infections. There was no association between IL-13 concentrations or IL-13 rs1800925 variants and risk of prostate cancer indicating that IL-13 levels and IL-13 rs10800925 may not be utilised as biomarker for risk of prostate cancer in schistosome infections.

A Systematic Review of Serum γ-Glutamyltransferase as a Prognostic Biomarker in Patients with Genitourinary Cancer.

γ-Glutamyltransferase (GGT), a membrane-bound enzyme, contributes to the metabolism of glutathione (GSH), which plays a critical physiological role in protecting cells against oxidative stress. GGT has been proposed as a biomarker of carcinogenesis and tumor progression given that GGT activity is important during both the promotion and invasion phases in cancer cells. Moreover, GGT expression is reportedly related to drug-resistance possibly because a wide range of drugs are conjugated with GSH, the availability of which is influenced by GGT activity. While serum GGT activity is commonly used as a quick, inexpensive, yet reliable means of assessing liver function, recent epidemiological studies have shown that it may also be an indicator of an increased risk of prostate cancer development. Moreover, elevated serum GGT is reportedly an adverse prognostic predictor in patients with urologic neoplasms, including renal cell carcinoma, prostate cancer, and urothelial carcinoma, although the background mechanisms have still not been well-characterized. The present review article summarizes the possible role of GGT in cancer cells and focuses on evidence evaluation through a systematic review of the latest literature on the prognostic role of serum GGT in patients with genitourinary cancer.

Organochlorine pesticide exposure and risk of prostate cancer development and progression: a systematic review

Background: There is an increasing body of evidence linking the exposure of an individual to pesticides such as organochlorine pesticides (OPCs) and an increased risk of developing diseases such as cancer. Exposure to OPCs has been suggested to increase the risk of developing hormone-dependant cancers such as prostate cancer (PCa). However, there is a relative paucity of information about the influence of exposure to these pesticides on the evolution of PCa, including risk of tumour development, progression to metastasis, and disease recurrence following therapy. Methods: We used several databases such as PubMed MEDLINE Database, Web of Science, and Scopus, in order to conduct a systematic review of the available epidemiological data implicating an association between exposure to OCPs and biochemical recurrence (BCR) of PCa. We searched all peer-reviewed articles published up to July 31st 2020. Pre-defined eligibility criteria for the inclusion of studies were that they be original studies, reviews, previous meta-analyses, or case–control or cohort studies. Results: Agent Orange is the most widely-studied OCP in the context of any possible causal role in the recurrence of PCa following radical prostatectomy, or in the progression to advanced disease. Only two studies didn’t demonstrate a significant association between exposure to OCPs and subsequent BCR following radical prostatectomy. Another study identified a significant association between exposure to Oxychlordane and PCB44 and progression to advanced PCa. Conclusion: This review confirmed a relative lack of high-quality evidence regarding this topic. However, the available evidence to date suggests the presence of a potential causal relationship between exposure to OPCs and PCa development and progression.

Association between estrogen receptor β polymorphisms and prostate cancer in a Slovak population.

Sex steroid hormones have important roles in the function of the prostate; however, they may also serve as factors in the initiation and progression of carcinogenesis. Estrogens, acting through estrogen receptors, may significantly affect prostate cancer development and progression. The main aim of the present study was to analyze the association between the rs3020449, rs4986938 and rs1256049 polymorphisms in the promoter region of the estrogen receptor β (ESR2) gene and prostate cancer risk in the Slovak population. A total of 510 patients with prostate cancer and 184 healthy men were included in the present study. No association between the rs4986938 and rs1256049 polymorphisms and prostate cancer development and progression was revealed; however, there was a statistically significant association between the rs3020449 GG genotype [odds ratio (OR), 2.35; P=0.002] and the G allele (OR, 1.42; P=0.005) and a higher risk of prostate cancer development. The rs3020449 GG genotype was significantly associated with a higher risk of development of carcinoma with a Gleason score >7 (OR, 2.66; P=0.005), as well as with the development of carcinoma with pT3/pT4 (OR, 2.28; P=0.02). According to the results from the present study, the rs3020449 polymorphism, in the promoter region of ESR2, may be considered to have a role in the development and progression of prostate cancer in the Slovak population.

Prostate cancer and androgenic alopecia: The role of finasteride as a dual agent

Background: Prostate cancer (PC) is recognised as the leading cancer diagnosis in Canadian men and the third-highest cause of cancer mortality. Despite its prevalence increasing with age, in Canada, funding for PC research is much lower when compared to other forms of cancer. Androgenic alopecia (AA) is a medical condition known to affect more than a third of all men and women. Studies show that AA is a medical condition with significant physical and psychological harms to the patient but one that can be treated effectively by a general practitioner. Objective: The objective is to determine the possibility of using finasteride to concurrently treat AA and prevent PC for men with more than one PC risk factor, one of which being AA. Methods: Numerous databases were searched, including OVID, Cochrane, Medline and PubMed. Additional internet searches were done using keywords such as dihydrotestosterone (DHT), AA, male pattern baldness, prostate-specific antigen, PC and finasteride, including a Medical Subject Headings search combining these words. Results and Conclusion: As a risk indicator for a PC diagnosis, early recognition of AA is important. Considering AA in conjunction with other risk factors for PC provides a more accurate risk assessment for patients. Finasteride has been shown to be effective in treating AA. By reducing DHT, a determining factor of both AA and PC development, finasteride has been demonstrated to reduce the risk of PC development by 25%. Finasteride therapy is an effective, low-risk, AA treatment option with the benefit of protecting potentially more susceptible men from PC. Given its excellent safety profile, as demonstrated in long-term studies of benign prostatic hyperplasia treatment, finasteride should be offered routinely to men with AA.

Second primary neoplasms in patients with primary orbital lymphoma: a population‐based study 1992 to 2016

AbstractPurposeTo investigate, in a population‐based study, the risk of developing second primary neoplasms (SPNs) after a diagnosis of primary orbital lymphoma (OL).MethodsData on a cohort of patients with a diagnosis of primary OL as their first malignancy were extracted from the Surveillance, Epidemiology, and End Results US registry from 1992 to 2016. Observed‐to‐expected ratio of developing SPNs was calculated to estimate relative risk (RR) and associated 95% confidence interval (CI), which were compared to a reference population (RP) matched for age, sex, race, and calendar year.ResultsA total of 1063 patients with primary OL were identified, 14% of whom developed SPNs. Mean age at OL diagnosis was 66 years old, while that at a SPN diagnosis was 74. There was a significant 20% excess risk of SPNs development in OL patients compared to the RP (p &lt; 0.05). Two to 11 months after OL diagnosis, there was an increased risk of respiratory tract malignancies [RR: 3.2 (95% CI: 1.2–6.9); p &lt; 0.05], while 10–15 years after diagnosis, there was an increased risk of colorectal cancer [RR: 3.0 (95% CI: 1.1–6.4); p &lt; 0.05]. Stratification by sex revealed an increased risk of prostate cancer development in males [RR: 3.4 (95% CI: 1.1–8.0); p &lt; 0.05]. Patients aged 40–59 years old experienced the greatest burden of SPNs with a significant 46% excess risk compared to the RP (p &lt; 0.05). Radiotherapy‐treated patients were at a higher risk of thyroid SPNs [RR: 3.8 (95% CI: 1.04–9.6); p &lt; 0.05].ConclusionsPatients with primary OL experience a 20% increased risk of SPNs compared to the RP. Two to 11 months and 10–15 years after OL diagnosis mark an increased risk of respiratory tract and colorectal SPNs, respectively. Male OL patients tend to more readily develop prostate malignancies than the RP. Patients 40–59 years old display the highest risk of SPNs. Radiotherapy is associated with an increased risk of developing thyroid neoplasms. Patients who are diagnosed with primary orbital lymphoma should be followed with these risks in mind.BibliographySurveillance Research Program, National Cancer Institute SEER*Stat software (www.seer.cancer.gov/seerstat) version 8.3.6.1.

C-Reactive Protein is a Poor Marker of Baseline Inflammation in Prostate Cancer and Response to Radiotherapy or Androgen Ablation

C-Reactive Protein (CRP) is an acute phase reactant used as a general marker for inflammation. There is some evidence that elevated levels are associated with increased risk of prostate cancer development, PSA, Gleason score, and decreased response to chemotherapy and radiotherapy (RT). Available literature largely focuses on pre-therapeutic levels as a prognostic marker. We seek to establish whether CRP levels reflect inflammation caused by prostate cancer before and in response to RT with or without prior androgen ablation (AA). This study included 209 patients who had a CBC, PSA, and CRP taken at up to four different time points. Labs were performed prior to AA via leuprolide injection (pre-AA), up to one week prior to RT (pre-RT), during the final week of RT (post-RT), and 3 months following RT completion (FU). Prior to RT, 33% of patients had received prior prostatectomy and 50.7% had received AA. Radiation fields included pelvic lymph nodes in 82% of patients. For comparisons at each time point, CRP had a significant relationship with WBCs pre-AA (p-value = 0.0050), pre-RT (p-value = 0.0170), and post-RT (p-value = 0.0113), but not at FU (p = .096). CRP had no significant relationship with PSA at any time points. For those who did or did not receive AA, pre-RT mean PSA was significantly lower (2.3 vs 5.4, p-value = 0.0072) while CRP was not. Pre-AA, pre-RT, and post-RT CRP levels were not significantly related to FU-PSA. No CRP levels were associated with risk groups. Only PSA significantly changed from pre-AA to pre-RT (p-value<0.0001). PSA, WBCs, and lymphocytes significantly decreased from pre-RT to post-RT, with significant recovery from post-RT to FU (p-value<0.0001 for all six comparisons), though still with overall significant change from pre-RT to FU (p-value = 0.0054, p-value<0.0001, p-value<0.0001, respectively). CRP did not significantly change during any period, nor significantly relate to changes in WBCs or PSA. There was a significant difference between the treated vs. untreated lymph node groups in post-RT lymphocytes (p-value<0.0001), FU-lymphocytes (p-value<0.0001), post-RT-WBCs (p-value = 0.0004), and FU-WBCs (p-value = 0.0141). CRP was not significantly different between these groups. Our results demonstrate a lack of clinical utility for CRP as a marker of the inflammatory effects of prostate cancer. It has no correlation with PSA levels or trends, before or after radiation therapy, with or without androgen ablation. It does not change with significant PSA decrease after androgen ablation and corresponding decrease in cancer activity. It does not change at the end of radiation therapy despite significant changes in lymphocytes and WBCs. It does not change with 3-month follow-up to correspond with either significant recovery of lymphocytes and WBCs or a decrease of radiation-induced inflammation.

Association of schistosomiasis and risk of prostate cancer development in residents of Murehwa rural community, Zimbabwe

BackgroundProstatic male genital schistosomiasis and prostate cancer co-existence cases are uncommon however, some studies have indicated that schistosomiasis may trigger development of prostate cancer regardless of age. Schistosomiasis is a public health problem in sub-Saharan Africa and may account for some undocumented cases of schistosomiasis prostatic cancer in schistosome endemic rural communities. It is against this background that we investigated the association between schistosomiasis and risk of prostate cancer development in residents of Murehwa Community, a schistosomiasis endemic area.MethodologyWe conducted a cross sectional study involving 366 men residing in Murehwa District, Zimbabwe. Schistosoma haematobium and S. mansoni infection was diagnosed using urine filtration and Kato Katz techniques, respectively. Haematuria was detected using urinalysis reagent strip test. A structured questionnaire was used to obtain history of schistosomiasis infection among study participants. Risk of prostate cancer development was assessed by measuring prostate-specific antigen levels in serum using the ELISA.ResultsPrevalence of S. haematobium and S. mansoni infection was 12.3% and 1.4%, respectively. Individuals with schistosomiasis had higher prostate-specific antigen levels (mean 1.208 ± SD 1.557 ng/mL) compared to those without schistosomiasis (mean 0.7721 ± SD 1.173 ng/mL; p < 0.05). Older individuals > 50 years had higher prostate specific antigen levels (mean 0.7212 ± SD 1.313 ng/mL) compared to individuals < 50 years old (mean 0.4159 ± SD 0.8622 ng/mL; p < 0.05). Prostate-specific antigen levels log10 (mean 0.2584 ± SD 0.2128 ng/mL) and were associated to S. haematobium infection intensity log10 (mean 1.121 ± SD 0.5371 eggs/10 mL), r(s) = − 0.3225, p < 0.05. There was a correlation between prostate-specific antigen levels log10 (mean 0.2246 ± SD 0.1858 ng/mL) and S. haematobium infection intensity log10 (mean 1.169 ± SD 0.5568 eggs/10 mL) among participants with a history of schistosomiasis infection (r(s) = − 0.3520; p < 0.05). There was no correlation between prostate-specific antigen levels of > 4 ng/mL (mean 5.324 ± SD1.568 ng/mL) and schistosome eggs log10 (mean 1.057 ± SD 0.6730 eggs/10 mL; p > 0.05).ConclusionUrogenital schistosome infections and history of schistosome infections were associated with prostate specific antigen levels, an indicator for risk of prostate cancer. Therefore, S. haematobium schistosome egg burden was associated with the risk of prostate cancer development in adult males residing in Murehwa District, Zimbabwe.

Milk Consumption and Prostate Cancer: A Systematic Review.

Prostate cancer is the third most common cancer in men globally, and the most common cancer among men in the United States. Dietary choices may play an important role in developing prostate cancer; in particular, a higher dairy product intake has been associated with an increased risk of developing prostate cancer. The overall positive association between milk consumption and the risk of prostate cancer development and prostate cancer mortality has been well documented in multiple epidemiological studies. However, there is limited literature on the association between types of milk, as classified by fat content (skim, low fat, and whole), and the risk of developing prostate cancer. When further examining current state of the literature on this topic, there is a number of epidemiologic studies assessing the relationship between prostate cancer and milk consumption. On the contrary, very few experimental studies explore this topic. Further experimental research may be necessary to examine the relationship between dairy and dairy products consumption and the increased risk of development of prostate cancer. At this time, there are no formal clinical recommendations regarding dairy products consumption for patients who are at risk of prostate cancer development or who have a history of prostate cancer. In this manuscript, we sought to systematically review the existing literature on the association between milk consumption classified by fat content, and the risk of developing prostate cancer. These findings may be useful for the clinicians who provide recommendations for the patients at risk of developing prostate cancer.

Prostate Carcinogenesis: Insights in Relation to Epigenetics and Inflammation.

Prostate cancer is a multifactorial disease that mainly occurs due to the accumulation of somatic, genetic, and epigenetic changes, resulting in the inactivation of tumor-suppressor genes and activation of oncogenes. Mutations in genes, specifically those that control cell growth and division or the repair of damaged DNA, make the cells grow and divide uncontrollably to form a tumor. The risk of developing prostate cancer depends upon the gene that has undergone the mutation. Identifying such genetic risk factors for prostate cancer poses a challenge for the researchers. Besides genetic mutations, many epigenetic alterations, including DNA methylation, histone modifications (methylation, acetylation, ubiquitylation, sumoylation, and phosphorylation) nucleosomal remodeling, and chromosomal looping, have significantly contributed to the onset of prostate cancer as well as the prognosis, diagnosis, and treatment of prostate cancer. Chronic inflammation also plays a major role in the onset and progression of human cancer, via modifications in the tumor microenvironment by initiating epithelialmesenchymal transition and remodeling the extracellular matrix. In this article, the authors present a brief history of the mechanisms and potential links between the genetic aberrations, epigenetic changes, inflammation, and inflammasomes that are known to contribute to the prognosis of prostate cancer. Furthermore, the authors examine and discuss the clinical potential of prostate carcinogenesis in relation to epigenetics and inflammation for its diagnosis and treatment..

Assessment of expression levels of leptin and leptin receptor as potential biomarkers for risk of prostate cancer development and aggressiveness.

BackgroundProstate cancer (PCa) is one of the most frequently diagnosed cancers worldwide. Despite the growing evidence associating obesity and adipokines, particularly leptin and its receptors, with cancer development and progression, it is still a debatable matter in PCa.ObjectivesWe aimed to assess the role of leptin and its receptors as potential biomarkers for the risk of PCa development and aggressiveness.MethodsIn this study, 176 men were included and categorized according to an established histopathological diagnosis into three age‐ and BMI‐matched groups. The PCa group included 56 patients while the BPH group and the control group comprised 60 men each. Serum levels of total PSA (tPSA) were assessed by ELISA and mRNA expression levels of leptin and leptin receptors were assessed by RT‐PCR.ResultsLeptin and leptin receptor mRNA expression levels were significantly higher in PCa patients relative to BPH and to healthy control men. Both were overexpressed in PCa patients with aggressive and distantly metastasizing tumors compared to patients with confined tumors. Leptin receptor mRNA was an independent predictor of high Gleason score ≥ 7, distant metastasis, LN, and seminal vesicles invasion.ConclusionLeptin and its receptors are suggested to be potential biomarkers for PCa; leptin receptor mRNA might predict risk and aggressiveness of PCa.

Does increased body mass index lead to elevated prostate cancer risk? It depends on waist circumference

BackgroundWe examined the association between obesity and prostate cancer based on both body mass index (BMI) and waist circumference (WC) using the National Health Insurance System (NHIS) database for the entire male population of Korea.MethodsA total of 1,917,430 men who underwent at least one health examination in 2009 without a previous diagnosis of any other cancer were tracked through December 2015. The hazard ratio (HR) and 95% confidence interval (CI) value for the association between prostate cancer and obesity were analyzed using multiple Cox regression model. Since there was a statistically significant interaction between WC and BMI, a multiple HR for prostate cancer was estimated with stratifying both WC and BMI to control the interaction between WC and BMI.ResultsWithout considering WC as an adjustment factor, very weak association between BMI and prostate cancer development risk was observed. When WC was considered as an adjustment factor, no significant change in the HRs for prostate cancer development beyond the reference BMI was observed in the group with WC < 85 cm in the multivariable-adjusted models. However, in the group with WC ≥ 85 cm, the HRs for prostate cancer increased as the BMI increased beyond the reference BMI. In addition, there was a discrepancy in the trend of prostate cancer development according to BMI among the groups with different categories for WC.ConclusionIn groups with abdominal obesity, a significant linear relationship was observed between increasing BMI and prostate cancer risk. Higher the WC category, the stronger was the association with BMI, signifying that the association of BMI with risk of prostate cancer development depends on abdominal obesity.

IL-18 Gene Polymorphisms Impacts on Its Serum Levels in Prostate Cancer Iraqi Patients

Prostate cancer is one of the most common types of cancer in men. A total of 110 Iraqi Arab individuals were included in this study; 60 individuals of them had prostate cancer with increased levels of TPSA (patients group); their age range 52-90 years. They were referred for diagnosis and treatment to the National Al-Amal Hospital for oncology in Baghdad during the period from July 2017 to October 2017. While the other 50 apparently healthy subjects were the control group, their age range similar to patients group. Sera and blood samples were collected from all patients and controls than used to assess for the level of IL-18 and DNA extraction, respectively. The polymorphisms were analyzed using polymerase chain reaction-single specific primer (PCR-SSP), at the position -137 G\C (rs187238) in the promoter of IL18 gene. The genetic polymorphism of the IL18 gene promoter -137G/C (rs187238) was determined and presented with three genotypes (GG, GC, and CC) in prostate cancer patients and controls. Testing for Hardy-Weinberg (H-W) equilibrium revealed that Prostate cancer patients showed insignificant variation in the distribution of IL-18 -137 genotypes (P&gt; 0.05). While the control samples showed significant variation (p ≤0.05) between the observed and expected. Comparing patients with controls indicated that IL-18-137 alleles or genotypes showed no association with the risk of prostate cancer development in Iraqi Arab population or protection against them. Serum level of IL-18 was highly significant (P ≤ 0.001) increased in patients compared to control. The IL-18 serum levels differences in GG and GC genotypes was significant (p &lt;0.05) between patients and control. While there were no significant differences between the three IL-18 -137 genotypes inpatient or in controls.

Associations Between Gene Polymorphisms of Vascular Endothelial Growth Factor and Prostate Cancer.

The aim of this study was to evaluate the association between selected polymorphisms of the vascular endothelial growth factor gene (rs699947, rs144854329, rs833061, rs2010963, rs3025039) and the risk of prostate cancer development and progression. The present study included 446 patients with prostate cancer and 241 healthy men. Genotyping was performed by polymerase-chain reaction-restriction fragment length polymorphism analysis. No significant association between the individual polymorphisms studied and the risk of prostate cancer development was detected. A statistically significantly increased risk of prostate cancer development associated with the presence of 9 or 10 risky alleles was found considering the whole group of patients, as well as in patients with low-grade carcinomas (Gleason score <7). Individual polymorphisms of VEGF do not appear to contribute to prostate cancer. However, a combination of risky alleles of the studied polymorphisms significantly increases the risk of prostate cancer in Slovak patients.