Sporadic Prostate Cancer Research Articles

Influence of family history on psychosocial distress and perceived need for treatment in prostate cancer survivors

Familial clustering is common in prostate cancer (PCa), but the psychosocial consequences of being a PCa patient in an affected family are not well understood. This study investigated the effects of family history of PCa on psychosocial distress and perceived psychosocial treatment need. Data were gathered within the German national research project "Familial Prostate Cancer". 4.123 PCa survivors who had undergone prostatectomy at least 4years ago received a questionnaire set. 3.623 of the respondents [68.3% sporadic, sporadic prostate cancer (SPCa); 31.7% familial, familial prosate cancer (FPCa)] filled in measures of cancer-specific distress (QSC-R10), depression (PHQ-2), and anxiety (GAD-2). Perceived psychosocial treatment need was assessed using a single item. The prevalence of psychosocial distress did not differ between SPCa and FPCa survivors (cancer-specific distress: 16.2 vs. 16.7%; depression: 5.8 vs. 6.4%; anxiety: 6.6 vs. 5.8%; ps≥.397). Similarly, psychosocial treatment need did not differ between SPCa (11.8%) and FPCa (13.1%) cases (p=.303). However, family history moderated the effect of cancer-specific distress on treatment need (OR 2.67, 95% CI 1.43-4.96, p=.002). Exploratory analyses for the hereditary subtype (HPCa) revealed that cancer-specific distress was lower in HPCa survivors who had only daughters compared to survivors without any children or with at least one son. No such effect was observed in SPCa survivors (p=.040). PCa survivors with a positive family history do not experience increased psychosocial distress. Nonetheless, family history may exert subtle effects that deserve further research.

Association between estrogen receptor alpha PvuII polymorphism and prostate cancer risk

Accumulating evidence has suggested that estrogen receptor alpha (ER-α) PvuII polymorphism might be involved in the development of prostate cancer (PCa). However, the results have been inconsistent. We therefore performed a meta-analysis to clarify the associations between ER-α PvuII polymorphism and PCa. A comprehensive search was conducted to identify all case-control studies of ER-α PvuII polymorphism and PCa risk. We used odds ratios (ORs) to assess the strength of the association and 95% confidence intervals (CIs) to give a sense of the precision of the estimate. A total of 14 studies were found to be eligible for meta-analyses of PvuII variant. Results from this study showed that ER-α PvuII polymorphism were significantly associated with PCa risk under all genetic models in overall population (homogeneous codominant model, OR = 1.57, 95% CI = 1.11-2.21, P = 0.010; heterogeneous codominant model, OR = 1.37, 95% CI = 1.06-1.77, P = 0.02; recessive model, OR = 1.27, 95% CI = 1.02-1.57, P = 0.03; dominant model, OR = 1.40, 95% CI = 1.09-1.79, P = 0.009; and allelic model, OR = 1.25, 95% CI = 1.06-1.48, P = 0.010). Further sensitivity analysis confirmed the significant association. In subgroup analyses stratified by PCa type, there was a significant association between PvuII polymorphism and sporadic PCa risk under both Caucasians and Asians. The meta-analysis indicated elected PvuII polymorphism of ER-α was a risk factor for PCa development.

Correction: Polymorphisms in the mTOR Gene and Risk of Sporadic Prostate Cancer in an Eastern Chinese Population

Affiliations numbers 1 and 3 for multiple authors are incorrect. The correct affiliation number 1 is: Cancer Institute, Fudan University Cancer Center, Shanghai, China. The correct affiliation number 3 is: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.

Androgen receptor mutations and polymorphisms in African American prostate cancer.

The Androgen receptor (AR) plays a central role in the normal development of the prostate gland, in prostate carcinogenesis, and in the progression of prostate cancer (PCa) to advanced metastatic disease. African American (AA) men with PCa present with higher tumor volume, more advanced tumor stage, and higher Gleason score. This could be in part related to the AR expression or activity in the prostate tissue of AA men, or to unique mutations or polymorphisms of the AR. In Caucasian Americans (CAs), AR mutations are rare or infrequent in organ-confined tumors, but occur at a higher rate in advanced, metastatic, or castrate-recurrent disease. In AAs, the prevalence, clinical, and biological significance of AR mutations in PCa are unknown. In this study, we investigated the occurrence of somatic and germline AR mutations in patients with primary PCa in AAs compared with CAs. Due to very limited data available on allelic distribution of E213 (G/A) single nucleotide polymorphism (SNP), we also assessed this in patients with sporadic PCa and in unrelated healthy individuals from both ethnic populations. Somatic missense AR mutations were detected at a higher rate in AAs (17 out of 200 cases) than in CAs (2 out of 100 cases). In AAs, the majority of these mutations (41.1%) were from Gleason 7 tumors, a small portion (23.5%) from Gleason 8 tumors, and the rest (35.2%) from Gleason 6 tumors. Analysis of genomic DNAs extracted from white blood cells of patients with sporadic PCa revealed that the rate of germline AR mutations were also higher (~4 times) in AAs than in CAs. With respect to E213 (G/A) SNP, the E213 A-allele expression was 5.85 times higher in healthy unrelated AA men than in CA men. However, in AAs with somatic AR mutation, the E213 G-allele distribution was almost equal to the A-allele. Silencing of one of the somatic AR mutations (i.e., 597 Ser>Gly) in a primary AA-PCa cell line (e.g., E006AA) revealed that similar AR mutation can be associated simultaneously with both “gain-of-function” phenotype (cell migration and invasion) and a “loss-of-function” phenotype (proliferation). Our data demonstrated a higher susceptibility for genetic alterations in the AR in the form of somatic mutations in sporadic PCa or in the form of germline mutations in AAs as compared with CAs. These data may support the idea that AR-specific hypermutator phenotype in combination with other genes, might serve as a contributing factor to ethnic differences in PCa and potentially different clinical outcome in AAs as a high-risk population.

Association of RNASEL and 8q24 variants with the presence and aggressiveness of hereditary and sporadic prostate cancer in a hispanic population

To study the association between the polymorphisms Arg462Gln and Asp541Glu from the RNASEL gene (1q25), and the polymorphisms rs620861, rs1447295, rs6983267, rs7837328 from the chromosome 8q24 with the risk of presenting prostate cancer (PCa) and its clinical characteristics in a Hispanic (Chilean) population. The study was performed on 21 control patients and 83 patients diagnosed with PCa. Polymorphisms were analysed from blood samples through real-time PCR by using TaqMan probes, and the genetic analysis was performed with the SNPStats program. Also, a comparison was performed between clinical characteristics of PCa and the presence of the different polymorphism genotypes by using the Minitab software. There was a significant association between the genotype G/G from the polymorphism rs6983267 with an overall increased risk of PCa, in patients both with or without family history of PCa (OR = 4.47, 95% CI = 1.05–18.94, P = 0.034 and OR = 3.57, 95% CI = 0.96–13.35, P = 0.037, respectively). Regarding clinical parameters, patients carrying the genotype C/C from the polymorphism Asp541Glu had significantly higher prostate-specific antigen (PSA) levels than patients carrying the other genotypes (P = 0.034). Moreover, patients with the genotype G/G of rs6983267 had higher PSA levels (P = 0.024). The polymorphism rs6983267 from region 3 of the chromosome 8q24 appears to be a prominent risk factor for PCa and a biomarker for cancer aggressiveness in the group of patients who presented higher levels of PSA at the time of diagnosis.

G84E mutation in HOXB13 is firmly associated with prostate cancer risk: a meta-analysis

The rare but recurrent germline G84E mutation in HOXB13 was recently found to be associated with a significantly increased risk of familial prostate cancer (PCa). However, epidemiologic findings have been inconsistent. In an attempt to confirm and expand the findings that the PCa risk increased in men carrying G84E, we therefore performed a meta-analysis to clarify the association between the germline G84E mutation and PCa risk. We also aim to verify the increased PCa risk with respect to diagnostic age, family history, and disease aggressiveness. Comprehensive search of databases was carried out, and other relevant articles were also identified. Then, the meta-analyses were conducted according to the standard guidelines. A total of 11 studies with 120,167 participants were included on the basis of inclusion criteria. The G84E allele carrier frequencies ranged from 0.1 to 4.9 % in the patients with PCa, as compared with 0 to 1.4 % in control subjects. Men with the HOXB13 G84E variant had a 4.51-fold higher relative risk of PCa compared with non-carriers (95 % CI 3.28-6.20). The much higher risks were observed in individuals with early onset (odds ratio (OR) = 9.73, 95 % confidence interval (CI) 6.57-14.39), more than two affected relatives (OR = 7.27, 95 % CI 4.02-13.15), and highly aggressive disease (OR = 5.81, 95 % CI 3.72-9.08). Our findings provide further evidences that the rare mutation in HOXB13 contributes to both hereditary and sporadic PCa risk. Despite the low G84E carrier rate, biological and clinical implications of the mutation in subjects with early onset, more than two affected relatives, and highly aggressive disease remain important in continued investigation.

Germline missense variants in the BTNL2 gene are associated with prostate cancer susceptibility.

Rare, inherited mutations account for 5% to 10% of all prostate cancer cases. However, to date, few causative mutations have been identified. To identify rare mutations for prostate cancer, we conducted whole-exome sequencing (WES) in multiple kindreds (n = 91) from 19 hereditary prostate cancer (HPC) families characterized by aggressive or early-onset phenotypes. Candidate variants (n = 130) identified through family- and bioinformatics-based filtering of WES data were then genotyped in an independent set of 270 HPC families (n = 819 prostate cancer cases; n = 496 unaffected relatives) for replication. Two variants with supportive evidence were subsequently genotyped in a population-based case-control study (n = 1,155 incident prostate cancer cases; n = 1,060 age-matched controls) for further confirmation. All participants were men of European ancestry. The strongest evidence was for two germline missense variants in the butyrophilin-like 2 (BTNL2) gene (rs41441651, p.Asp336Asn and rs28362675, p.Gly454Cys) that segregated with affection status in two of the WES families. In the independent set of 270 HPC families, 1.5% (rs41441651; P = 0.0032) and 1.2% (rs28362675; P = 0.0070) of affected men, but no unaffected men, carried a variant. Both variants were associated with elevated prostate cancer risk in the population-based study (rs41441651: OR, 2.7; 95% CI, 1.27-5.87; P = 0.010; rs28362675: OR, 2.5; 95% CI, 1.16-5.46; P = 0.019). Results indicate that rare BTNL2 variants play a role in susceptibility to both familial and sporadic prostate cancer. Results implicate BTNL2 as a novel prostate cancer susceptibility gene.

ARLTS1 and Prostate Cancer Risk - Analysis of Expression and Regulation

Prostate cancer (PCa) is a heterogeneous trait for which several susceptibility loci have been implicated by genome-wide linkage and association studies. The genomic region 13q14 is frequently deleted in tumour tissues of both sporadic and familial PCa patients and is consequently recognised as a possible locus of tumour suppressor gene(s). Deletions of this region have been found in many other cancers. Recently, we showed that homozygous carriers for the T442C variant of the ARLTS1 gene (ADP-ribosylation factor-like tumour suppressor protein 1 or ARL11, located at 13q14) are associated with an increased risk for both unselected and familial PCa. Furthermore, the variant T442C was observed in greater frequency among malignant tissue samples, PCa cell lines and xenografts, supporting its role in PCa tumourigenesis. In this study, 84 PCa cases and 15 controls were analysed for ARLTS1 expression status in blood-derived RNA. A statistically significant (p = 0.0037) decrease of ARLTS1 expression in PCa cases was detected. Regulation of ARLTS1 expression was analysed with eQTL (expression quantitative trait loci) methods. Altogether fourteen significant cis-eQTLs affecting the ARLTS1 expression level were found. In addition, epistatic interactions of ARLTS1 genomic variants with genes involved in immune system processes were predicted with the MDR program. In conclusion, this study further supports the role of ARLTS1 as a tumour suppressor gene and reveals that the expression is regulated through variants localised in regulatory regions.

Polymorphisms in the mTOR Gene and Risk of Sporadic Prostate Cancer in an Eastern Chinese Population

BackgroundThe mTOR gene regulates cell growth by controlling mRNA translation, ribosome biogenesis, autophagy, and metabolism. Abnormally increased expression of mTOR was associated with carcinogenesis, and its functional single nucleotide polymorphisms (SNPs) may regulate the expression of mTOR and thus contribute to cancer risk.Methodology/Principal FindingsIn a hospital-based case-control study of 1004 prostate cancer (PCa) cases and 1051 cancer-free controls, we genotyped six potentially functional SNPs of mTOR (rs2536 T>C, rs1883965 G>A, rs1034528 G>C, rs17036508 T>C, rs3806317 A>G, and rs2295080 T>G) and assessed their associations with risk of PCa by using logistic regression analysis.Conclusions/SignificancesIn the single-locus analysis, we found a significantly increased risk of PCa associated with mTOR rs2536 CT/CC and rs1034528 CG/CC genotypes [adjusted OR = 1.42 (1.13–1.78), P = 0.003 and 1.29 (1.07–1.55), P = 0.007), respectively], compared with their common homozygous genotypes, whereas mTOR rs2295080 GT/GG genotypes were associated with a decreased risk of PCa [adjusted OR = 0.76 (0.64–0.92), P = 0.003], compared with wild-type TT genotypes. In the combined analysis of the six SNPs, we found that individuals carrying two or more adverse genotypes had an increased risk of PCa [adjusted OR = 1.24 (1.04–1.47), P = 0.016], compared with individuals carrying less than two adverse genotypes. In the multiple dimension reduction analysis, body mass index (BMI) was the best one-factor model with the highest CVC (100%) and the lowest prediction error (42.7%) among all seven factors. The model including an interaction among BMI, rs17036508, and rs2536 was the best three-factor model with the highest CVC (100%) and the lowest prediction error of 41.9%. These findings suggested that mTOR SNPs may contribute to the risk of PCa in Eastern Chinese men, but the effect was weak and needs further validation by larger population-based studies.

The poly(ADP-ribose) polymerase inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with sporadic cancer: a phase 1 dose-escalation trial

Poly(ADP-ribose) polymerase (PARP) is implicated in DNA repair and transcription regulation. Niraparib (MK4827) is an oral potent, selective PARP-1 and PARP-2 inhibitor that induces synthetic lethality in preclinical tumour models with loss of BRCA and PTEN function. We investigated the safety, tolerability, maximum tolerated dose, pharmacokinetic and pharmacodynamic profiles, and preliminary antitumour activity of niraparib. In a phase 1 dose-escalation study, we enrolled patients with advanced solid tumours at one site in the UK and two sites in the USA. Eligible patients were aged at least 18 years; had a life expectancy of at least 12 weeks; had an Eastern Cooperative Oncology Group performance status of 2 or less; had assessable disease; were not suitable to receive any established treatments; had adequate organ function; and had discontinued any previous anticancer treatments at least 4 weeks previously. In part A, cohorts of three to six patients, enriched for BRCA1 and BRCA2 mutation carriers, received niraparib daily at ten escalating doses from 30 mg to 400 mg in a 21-day cycle to establish the maximum tolerated dose. Dose expansion at the maximum tolerated dose was pursued in 15 patients to confirm tolerability. In part B, we further investigated the maximum tolerated dose in patients with sporadic platinum-resistant high-grade serous ovarian cancer and sporadic prostate cancer. We obtained blood, circulating tumour cells, and optional paired tumour biopsies for pharmacokinetic and pharmacodynamic assessments. Toxic effects were assessed by common toxicity criteria and tumour responses ascribed by Response Evaluation Criteria in Solid Tumors (RECIST). Circulating tumour cells and archival tumour tissue in prostate patients were analysed for exploratory putative predictive biomarkers, such as loss of PTEN expression and ETS rearrangements. This trial is registered with ClinicalTrials.gov, NCT00749502. Between Sept 15, 2008, and Jan 14, 2011, we enrolled 100 patients: 60 in part A and 40 in part B. 300 mg/day was established as the maximum tolerated dose. Dose-limiting toxic effects reported in the first cycle were grade 3 fatigue (one patient given 30 mg/day), grade 3 pneumonitis (one given 60 mg/day), and grade 4 thrombocytopenia (two given 400 mg/day). Common treatment-related toxic effects were anaemia (48 patients [48%]), nausea (42 [42%]), fatigue (42 [42%]), thrombocytopenia (35 [35%]), anorexia (26 [26%]), neutropenia (24 [24%]), constipation (23 [23%]), and vomiting (20 [20%]), and were predominantly grade 1 or 2. Pharmacokinetics were dose proportional and the mean terminal elimination half-life was 36·4 h (range 32·8-46·0). Pharmacodynamic analyses confirmed PARP inhibition exceeded 50% at doses greater than 80 mg/day and antitumour activity was documented beyond doses of 60 mg/day. Eight (40% [95% CI 19-64]) of 20 BRCA1 or BRCA2 mutation carriers with ovarian cancer had RECIST partial responses, as did two (50% [7-93]) of four mutation carriers with breast cancer. Antitumour activity was also reported in sporadic high-grade serous ovarian cancer, non-small-cell lung cancer, and prostate cancer. We recorded no correlation between loss of PTEN expression or ETS rearrangements and measures of antitumour activity in patients with prostate cancer. A recommended phase 2 dose of 300 mg/day niraparib is well tolerated. Niraparib should be further assessed in inherited and sporadic cancers with homologous recombination DNA repair defects and to target PARP-mediated transcription in cancer. Merck Sharp and Dohme.

A2 Allele Polymorphism of the CYP17 Gene and Prostate Cancer Risk in an Iranian Population

Studies have shown that alterations of steroid hormone metabolism, particularly involving testosterone, affect the risk of prostate cancer. Therefore, genetic variation in genes of enzymes which are involved could be of importance. The gene most interest is CYP17, whose enzyme product has an essential role in testosterone hormone synthesis. Some studies have indicated that the A2 allele polymorphism of CYP17 associated with increased risk of prostate cancer that could be affected by ethnicity. Therefore, the aim of this study was determination of presence or absence of the A2 allele in patients with prostate cancer. We studied the association of A2 allele and prostate cancer among 74 patients with prostate cancer and 128 healthy men which were referred to hospitals of SBMU. This study revealed a significant association between prostate cancer risk and the A2 allele in an Iranian population so that A1A2 and A2A2 genotypes were more common in cases than controls with P-values of 0.029 and 0.010, respectively. Results of our study support a possible role of the A2 allele in sporadic prostate cancer development in Iran, in line with findings elsewhere.

Steroid 5-alpha-reductase type 2 (SRD5A2) V89L and A49T polymorphisms and sporadic prostate cancer risk: a meta-analysis

Steroid 5-α-reductase type 2 (SRD5A2) V89L and A49T polymorphisms are thought to play a crucial role in the androgen synthesis and metabolic pathway, but their associations with prostate cancer risk remain controversial. To provide a more precise estimation of the associations between V89L and A49T polymorphisms and prostate cancer risk, we performed a meta-analysis using all published case-control studies of prostate cancer since January 1995. We used odds ratio (OR) and its 95% confidence interval (CI) to assess the strength of the association under various genetic models in both overall and stratified analyses. We also calculated the false-positive report probability, the power of the current study, and the observed P value for significant findings. This analysis included 45 eligible studies of a total of 15,562 cases and 15,385 controls, in which no significant associations were found for the V89L polymorphisms under all genetic models. However, small excess prostate cancer risk was associated with the 49T allele in mixed populations compared with the 49A allele (OR = 1.24, 95% CI = 1.02-1.50), and similar results were observed in Caucasians (OR = 1.24, 95% CI = 1.01-1.53). The sensitivity analysis further strengthened the validity of these findings without publication bias. Although there was no overall association between V89L and prostate cancer risk, A49T might play a role in the etiology of prostate cancer among Caucasians. Additional large and well-designed studies are warranted to validate these findings.

RNase L Variants Do Not Appear to Impact on Clinical Features of Sporadic Prostate Cancer Patients

Introduction: Prostate cancer is the most common non-cutaneous male cancers, contributing to significant mortality rates globally. Mutations of RNase L, an enzyme involved in inflammatory and immunological pathways, have been speculated to predispose to cancer. This study assesses three different mutations of the RNase L gene in Irish prostate cancer patients, including one linked with general cancer susceptibility never investigated before in prostate cancer (rs3738579), and reports on links with aggressive cancer. Methods: 134 patients had their RNase L mutation status determined by polymerase chain reaction (PCR) of serum DNA. Complementary clinical details for each patient are statistically analysed. Results: No link to age of diagnosis, high grade disease or prostate specific antigen (PSA) level at diagnosis was demonstrated with any of the studied single nucleotide polymorphisms (SNP). The SNP variation was consistent with that of published international series. Conclusion: SNP genotypic frequencies in Ireland are consistent with international findings. The studied RNase L mutations including rs3738579 do not appear to have a significant impact on our patient population.

Genetic Variations ofα-Methylacyl-CoA Racemase Are Associated with Sporadic Prostate Cancer Risk in Ethnically Homogenous Koreans

Background. To assess if the variants of (R)-alpha-methyl-CoA racemase (AMACR) gene would be associated with the risk of sporadic prostate cancer in ethnically homogenous Koreans. Materials and Methods. We enrolled 194 patients with prostate cancer and 169 healthy controls. A total of 17 single nucleotide polymorphisms of the AMACR gene were selected. The distribution of each genotype and haplotype was analyzed and their association with the incidence of prostate cancer was evaluated. Further, we detected AMACR expression in tumor with immunohistochemistry and analyzed its association with genotype regarding prostate cancer risk. Results. AG or GG genotype of rs2278008 (E277K) tended to lower prostate cancer risk. The minor G allele was found to be a significant allele that decreased the risk of prostate cancer (adjusted OR, 0.57; 95% CI, 0.35–0.93, P value = 0.025). In patients expression AMACR, AG or GG genotype was also significant genotype in terms of prostate cancer risk (adjusted OR, 0.47; 95% CI, 0.26–0.87, P value = 0.017). Further, [GGCGG] haplotype consisted of five coding SNPs of rs2278008, rs34677, rs2287939, rs10941112, and rs3195676 which decreased the risk of prostate cancer (P value = 0.047). Conclusions. Genetic variations of AMACR are associated with the risk of sporadic prostate cancer that underwent radical prostatectomy in Koreans.

Association between Mismatch Repair Gene MSH3 codons 1036 and 222 Polymorphisms and Sporadic Prostate Cancer in the Iranian Population

The mismatch repair system (MMR) is a post-replicative DNA repair mechanism whose defects can lead to cancer. The MSH3 protein is an essential component of the system. We postulated that MSH3 gene polymorphisms might therefore be associated with prostate cancer (PC). We studied MSH3 codon 222 and MSH3 codon 1036 polymorphisms in a group of Iranian sporadic PC patients. A total of 60 controls and 18 patients were assessed using the polymerase chain reaction and single strand conformational polymorphism. For comparing the genotype frequencies of patients and controls the chi-square test was applied. The obtained result indicated that there was significantly association between G/A genotype of MSH3 codon 222 and G/G genotype of MSH3 codon 1036 with an increased PC risk (P=0.012 and P=0.02 respectively). Our results demonstrated that MSH3 codon 222 and MSH3 codon 1036 polymorphisms may be risk factors for sporadic prostate cancer in the Iranian population.

Mitochondrial Haplogroups and Polymorphisms Reveal No Association with Sporadic Prostate Cancer in a Southern European Population

BackgroundIt is known that mitochondria play an important role in certain cancers (prostate, renal, breast, or colorectal) and coronary disease. These organelles play an essential role in apoptosis and the production of reactive oxygen species; in addition, mtDNA also reveals the history of populations and ancient human migration. All these events and variations in the mitochondrial genome are thought to cause some cancers, including prostate cancer, and also help us to group individuals into common origin groups. The aim of the present study is to analyze the different haplogroups and variations in the sequence in the mitochondrial genome of a southern European population consisting of subjects affected (n = 239) and non-affected (n = 150) by sporadic prostate cancer.Methodology and Principal FindingsUsing primer extension analysis and DNA sequencing, we identified the nine major European haplogroups and CR polymorphisms. The frequencies of the haplogroups did not differ between patients and control cohorts, whereas the CR polymorphism T16356C was significantly higher in patients with PC compared to the controls (p = 0.029). PSA, staging, and Gleason score were associated with none of the nine major European haplogroups. The CR polymorphisms G16129A (p = 0.007) and T16224C (p = 0.022) were significantly associated with Gleason score, whereas T16311C (p = 0.046) was linked with T-stage.Conclusions and SignificanceOur results do not suggest that mtDNA haplogroups could be involved in sporadic prostate cancer etiology and pathogenesis as previous studies performed in middle Europe population. Although some significant associations have been obtained in studying CR polymorphisms, further studies should be performed to validate these results.

Potential predictors of fear of progression among long-term prostate cancer survivors: Do illness perceptions and family history matter?

e15157 Background: Fear of illness progression (FoP) or recurrence is known to be one of the most prominent fears in patients with prostate cancer (PCa) even years after treatment. To improve detection of men at risk, possible predictors need to be discovered. So far, little is known about the influence of patients' illness perceptions (IP) and family history on dysfunctional FoP (dysFoP). Methods: A nationwide mail survey was sent out to a total of 6.305 men who had been treated with radical prostatectomy. Median time since diagnosis was 7.4 years. Patients were divided into 2 subgroups according to their family history: 68.9% (n=4.341) sporadic and 31.1% (n=1.964) familial (at least 1 first-degree relative with PCa). FoP was assessed with the short form of the Fear of Progression Questionnaire (FoP-Q-SF), IP were assessed with the Brief Illness Perception Questionnaire (B-IPQ). We also evaluated sociodemographic and clinical parameters and their influence on FoP. Results: Dysfunctional FoP was identified in 3.4% of all patients. Patients worried most about family, being dependent on others, and whether the children would also be diagnosed with PCa. Younger age, worse subjective economic situation, shorter time since diagnosis and disease progression were significantly associated with dysFoP (p<.01). IP and prevalence of dysFoP did not differ significantly between patients with sporadic and familial PCa, but familial PCa was associated with a higher mean level of FoP. IP explained a high amount of variance in FoP (R²=.435). Stronger perceptions of worry and negative emotions were significant predictors of FoP (p<.001). Furthermore, having at least one son (p=.004), time since diagnosis <5 years (p=.006) and worse subjective economic situation (p=.030) were predictive of dysFoP. Conclusions: In this study only a minority of patients reported dysFoP. The study findings suggest the importance of addressing IP, especially worries, negative emotions, and perceived consequences as key factors of FoP. Prevalence of dysFoP did not differ depending on family history, however patients with familial PCa showed higher mean levels of FoP.

RNASEL study of genetics of prostate cancer and its relation to clinical staging

ObjectivesThis study has aimed to find a possible genetic relationship between sporadic prostate cancers. An attempt is made to establish population subgroups in patients based on the genotype found and the aggressiveness of the cancer. Materials and methodsA total of 231 patients with sporadic prostate cancer and 68 controls were selected. The subjects were selected by an urologist using clinical parameters such as Prostate Specific Antigen (PSA) level and Gleason score. Both groups (patients and controls) were genotyped in RNASEL gene by sequencing the exons 1 and 3. ResultsStatistically significant differences were found between controls and patients in some of the genotyped regions of the RNASEL gene (I97L, D541E and R462Q). ConclusionsThanks to the genetic profile in some regions of the genoma, such as the RNASEL gene, together with the combination of the clinical and environmental parameters, we can suggest a care and more personalized follow-up of each patient.

Prostate cancer risk and aggressiveness associated with the CYP1B1 4326C/G (Leu432Val) polymorphism: a meta-analysis of 2788 cases and 2968 controls

To derive a precise estimation of the associations between the cytochrome P450 1B1 (CYP1B1) 4326C/G variants and prostate cancer (PCa) risk or aggressiveness, a meta-analysis was performed using all eligible published studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association in seven literature studies with 2788 cases and 2968 controls. In the overall analysis, no significant association was found between the CYP1B1 4326C/G polymorphism and PCa risk, but ethnicity subgroup analyses and a case-source analysis revealed significant associations. The 4326G allele showed a significant association with increased PCa risk in Asians (OR=1.52, 95% CI: 1.20-1.92), and significant associations were also observed in a heterozygote comparison (OR=1.40, 95% CI: 1.03-1.89), a homozygote comparison (OR=2.38, 95% CI: 1.31-4.33) and in a dominant genetic model (OR=1.52, 95% CI: 1.14-2.01). Moreover, the 4326G allele was also significantly correlated with an increased risk of sporadic PCa (OR=1.13, 95% CI: 1.04-1.24), and significant associations were observed in a heterozygote comparison (OR=1.16, 95% CI: 1.02-1.33), a homozygote comparison (OR=1.24, 95% CI: 1.03-1.49) and a dominant genetic model (OR=1.19, 95% CI: 1.05-1.34). The overall analyses and all subgroup analyses showed no significant association between the 4326C/G polymorphism and PCa aggressiveness. Our meta-analysis showed that CYP1B1 4326G allele is significantly associated with an increased PCa risk in Asians and in sporadic PCa cases.

Association of chromosome 8q24 variants with prostate cancer risk in the Siberian region of Russia and meta-analysis

Compelling evidence demonstrates chromosome 8q24 as a prostate cancer susceptibility locus. In present work we studied whether the common variants of 8q24 region, rs6983267 and rs1447295, were associated with the sporadic prostate cancer risk in the Russian population. Polymorphisms were genotyped in 393 case and 384 control Russian Caucasian men from Siberia region. The A allele of rs1447295 was significantly associated with the risk of prostate cancer (OR[CI 95%] = 1.74 [1.26-2.4], p = 7.8 x 10(-4)). A common G-A haplotype for rs6983267 - rs1447295 also showed an association with prostate cancer risk in Russian population (OR[CI 95%] = 2.03 [1.1 - 3.75], p = 0.02). We performed a meta-analysis combining our results with previous studies to evaluate the association between studied SNPs and prostate cancer risk. Meta-analysis has strongly supported the association for these SNPs (p < 10(-6)). Accordingly our study confirms the association between chromosome 8q24 and prostate cancer risk.