Relative Risk Of Prostate Cancer Research Articles

Polygenic risk for prostate cancer: Decreasing relative risk with age but little impact on absolute risk

Polygenic risk scores (PRSs) for a variety of diseases have recently been shown to have relative risks that depend on age, and genetic relative risks decrease with increasing age. A refined understanding of the age dependency of PRSs for a disease is important for personalized risk predictions and risk stratification. To further evaluate how the PRS relative risk for prostate cancer depends on age, we refined analyses for a validated PRS for prostate cancer by using 64,274 prostate cancer cases and 46,432 controls of diverse ancestry (82.8% European, 9.8% African American, 3.8% Latino, 2.8% Asian, and 0.8% Ghanaian). Our strategy applied a novel weighted proportional hazards model to case-control data to fully utilize age to refine how the relative risk decreased with age. We found significantly greater relative risks for younger men (age 30-55 years) compared with older men (70-88 years) for both relative risk per standard deviation of the PRS and dichotomized according to the upper 90th percentile of the PRS distribution. For the largest European ancestral group that could provide reliable resolution, the log-relative risk decreased approximately linearly from age 50 to age 75. Despite strong evidence of age-dependent genetic relative risk, our results suggest that absolute risk predictions differed little from predictions that assumed a constant relative risk over ages, from short-term to long-term predictions, simplifying implementation of risk discussions into clinical practice.

Prostate cancer incidence and survival in relation to prostate cancer as second cancer in relatives.

ObjectivesTo investigate if the risk of prostate cancer (PC) differs based on the order of primary PC diagnosed in first‐degree relatives (FDRs) given possibly different risk factors for PC as first primary cancer (PCa‐1) and second primary cancer (PCa‐2).Subjects and MethodsIn this Swedish nationwide cohort, PC diagnosis was followed for among 149,985 men with one FDR affected by PCa‐1, 10,972 with one FDR affected by PCa‐2 and 2,896,561 without any FDRs affected by cancer in a maximum of 57 years. PC patients were further followed for death due to PC since diagnosis. Relative risk (RR) of PC was estimated with Poisson regression and hazard ratio (HR) with Cox proportional hazard model.ResultsCompared to men without any FDRs affected by cancer, the RRs of PC in men with one FDR affected by PCa‐1 and PCa‐2 were 2.12 (95% confidence interval [CI]: 2.07–2.17) and 1.69 (1.54–1.85), respectively. The risk in men with one FDR affected by PCa‐2 was significantly lower than those with one FDR affected by PCa‐1 after additionally adjusting for family relationship (father‐son and brothers) and age at diagnosis of PC in FDR (RR PCa‐2 vs PCa‐1, 0.85, 95% CI, 0.78–0.94). PC patients with a family history of PCa‐2 were more likely to be detected at late‐stage and less likely to be diagnosed by screening, compared to those with a family history of PCa‐1. Patients whose PC was diagnosed after the diagnosis of PCa‐1 in FDRs had a better survival than those without a family history of cancer (HR, 0.88, 95% CI, 0.80–0.97), but no such association was observed among patients with a family history of PCa‐2.ConclusionOur study indicates a discrepancy between PC risks associated with a family history of PCa‐1 and PC‐2 and the reason behind it may be multifactorial.

The Association between Dietary Diversity Score and Risk of Prostate Cancer: (A Case-Control Study)

There are few studies that evaluated the relationship between dietary diversity score (DDS) and risk of cancer. The purpose of this study was to examine the association of DDS with the risk of prostate cancer (PC) among Iranian men. This case-control study was performed among 60 cases with prostate cancer and 60 hospital-based controls. Anthropometric measurements were done and demographic information was recorded using standard protocols. A validated 160-item semi-quantitative food frequency questionnaire (FFQ) was used to assess usual dietary intakes. Also, Binary logistic regression was performed to estimate the risk of PC in relation to DDS. After controlling for several confounders (age, body mass index, physical activity, energy intake, job, education, and antihypertensive drugs usage) higher adherence to DDS (OR = 0.33; 95% CI (0.11-0.97)), fruits group (OR = 0.19; 95% CI (0.06-0.63)), and vegetables group (OR = 0.17; 95% CI (0.05 − 0.58)) were significantly associated with lower risk of PC. In contrast, greater adherence to the meat group (OR = 3.88; 95% CI (1.32-11.42)) was significantly associated with increased PC risk. Our results showed that adherence to a diet with higher DDS, especially higher amounts of fruits and vegetables and a lower amount of meat could decrease the risk of PC.

Geospatial analysis, web-based mapping and determinants of prostate cancer incidence in Georgia counties: evidence from the 2012\u20132016 SEER data

BackgroundProstate cancer (CaP) cases are high in the United States. According to the American Cancer Society, there are an estimated number of 174,650 CaP new cases in 2019. The estimated number of deaths from CaP in 2019 is 31,620, making CaP the second leading cause of cancer deaths among American men with lung cancer been the first. Our goal is to estimate and map prostate cancer relative risk, with the ultimate goal of identifying counties at higher risk where interventions and further research can be targeted.MethodsThe 2012–2016 Surveillance, Epidemiology, and End Results (SEER) Program data was used in this study. Analyses were conducted on 159 Georgia counties. The outcome variable is incident prostate cancer. We employed a Bayesian geospatial model to investigate both measured and unmeasured spatial risk factors for prostate cancer. We visualised the risk of prostate cancer by mapping the predicted relative risk and exceedance probabilities. We finally developed interactive web-based maps to guide optimal policy formulation and intervention strategies.ResultsNumber of persons above age 65 years and below poverty, higher median family income, number of foreign born and unemployed were risk factors independently associated with prostate cancer risk in the non-spatial model. Except for the number of foreign born, all these risk factors were also significant in the spatial model with the same direction of effects. Substantial geographical variations in prostate cancer incidence were found in the study. The predicted mean relative risk was 1.20 with a range of 0.53 to 2.92. Individuals residing in Towns, Clay, Union, Putnam, Quitman, and Greene counties were at increased risk of prostate cancer incidence while those residing in Chattahoochee were at the lowest risk of prostate cancer incidence.ConclusionOur results can be used as an effective tool in the identification of counties that require targeted interventions and further research by program managers and policy makers as part of an overall strategy in reducing the prostate cancer burden in Georgia State and the United States as a whole.

Relative risks of prostate cancer associated with different family cancer histories.

1505 Background: Recently developed clinical guidelines have suggested that men in families with Hereditary Prostate Cancer (HPC), Hereditary Breast and Ovarian Cancer (HBOC), and Lynch Syndrome (LS) be referred for consideration of genetic testing, especially in the setting of aggressive disease. However, while a family history (FH) of the same disease among close relatives is an established risk factor for prostate cancer (PC), a direct comparison of risk associated with specific FH, and particularly with respect to known familial cancer syndromes, in a single population is needed. Methods: The Utah Population Database was used to identify 569,320 men, 40+ years with a pedigree that included at least three consecutive generations. Each man was evaluated for FH of FPC, HPC, HBOC and LS, as well as their own PC status. PC cases (N=34,889) were identified from both the SEER Utah Cancer Registry and death certificates and classified into one or more subtypes: early-onset (EO [age of diagnosis <60 years]), lethal, and/or aggressive (Gleason Grade ≥7, metastatic, or lethal). Relative risks (RR) associated with each PC subtype, adjusted for important covariates, were calculated in STATA using a modified Poisson regression with robust error variances to obtain corresponding confidence intervals (CIs) for each FH definition. Results: A FH of HPC conveyed the greatest relative risk for all PC subtypes (RR=2.30; 95% CI 2.21-2.39), followed by HBOC and LS. Furthermore, the strongest risks associated with FH were generally observed for EO disease. No differences in risk by degree of FH were observed for either lethal or aggressive disease. Conclusions: In this large population-based family database, the risk of PC was shown to vary by cancer FH and was most strongly associated with EO disease. These results are critically valuable in understanding and targeting high-risk populations that would benefit from genetic screening and enhanced surveillance. [Table: see text]

Vitamin K intake and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial

Vitamin K inhibits prostate cancer cells, and an altered expression of vitamin K-dependent proteins in prostate tumors has been linked to their aggressiveness and progression. However, little is known about the effect of vitamin K intake on prostate cancer in human populations. We evaluated the associations of dietary intake of phylloquinone (vitamin K-1), menaquinones (vitamin K-2), and total vitamin K with the development of prostate cancer among participants in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial. Dietary intake of vitamin K was assessed with the Dietary Questionnaire (DQX) at baseline and the Dietary History Questionnaire (DHQ) at the third anniversary of randomization by using high-performance liquid chromatography-based food-composition data obtained from the USDA and published studies. During a median follow-up of 11.8 y, 2978 cases of prostate cancer (including 490 advanced cases) were identified from the 28,356 men who completed DQX. Similarly, 2973 cases of prostate cancer (including 647 advanced cases) were documented from the 48,090 men who completed DHQ. Cox proportional hazards regression was used to estimate prostate cancer risk in relation to the dietary intake of vitamin K. After adjustment for confounders, dietary intakes of phylloquinone, menaquinones, and total vitamin K, assessed with either the DQX or DHQ, were not significantly associated with the risk of advanced, nonadvanced, and total prostate cancer. These results remained virtually the same when vitamin K intake was modeled as a categorical (divided into quintiles) or continuous (per IQR increase) variable or after outliers of total vitamin K intake (defined as a value that falls above the sum of third quartile and twice the IQR) were excluded. The present study does not suggest that vitamin K intake influences the occurrence of total and advanced prostate cancer in the general US population.

Antihypertensive drugs and prostate cancer risk in a Finnish population-based cohort

Background: The etiology of prostate cancer (PCa) involves environmental and genetic factors. Understanding the role of medication use on PCa risk may clarify the pathophysiological changes and mechanisms in development of cancer.Methods: This study investigated PCa risk in relation to overall use of anti-hypertensive drugs and those with specific mechanisms of action. The study cohort (78,615 men) was linked to the prescription database to obtain information on medication use during 20-year follow-up. Information was obtained on PCa diagnoses, causes of deaths, and for a sub-set on B.M.I. and use of non-prescription drugs. Time-dependent drug use variables hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox regression analyses.Results: Use of antihypertensive drugs slightly increased PCa risk (HR = 1.16, 95% CI = 1.11–1.22). The risk increase was clearest for metastatic PCa (HR = 1.36, 95% CI = 1.14–1.62). ACE inhibitors, beta-blockers, and diuretics were all separately associated with a small excess risk (HR = 1.10, 95% CI = 1.01–1.19, HR = 1.14, 95% CI = 1.06–1.21, and HR = 1.16, 95% CI = 1.07–1.27, respectively). None of the other groups showed a clear association with PCa risk.Conclusions: The use of antihypertensive drugs was associated with increased prostate cancer risk. Similar risk association for multiple drug groups suggests that the findings may not reflect a direct medication effect, but may be due to underlying hypertension.

The clinical usefulness of natural killer cell activity in patients with suspected or diagnosed prostate cancer: an observational cross-sectional study.

PurposeTo investigate the clinical usefulness of natural killer cell activity (NKA) for detection of prostate cancer (PCa) and prediction of Gleason grade.Patients and methodsWe prospectively enrolled 221 patients who underwent transrectal ultrasound-guided prostate biopsy for suspected PCa due to elevated prostate-specific antigen (PSA) >2.5 ng/mL or abnormal findings on digital rectal examination (n=146), or who were diagnosed with PCa (n=75) between 2016 and 2017. The NKA was compared according to PCa and Gleason grade. Correlation analysis was used to evaluate associations among NKA, PCa, and Gleason grade, and expressed using distribution dot plots. The absolute risk and relative risk of PCa, and odds ratios at different cut-off values of NKA were calculated.ResultsOf the total 221 patients, PCa was identified in 135 (61.9%) patients. When patients were divided according to PCa, there was no significant difference in NKA (1,267.6 vs 1,198.9 pg/mL, P=0.491). Furthermore, in 135 patients with PCa, the NKA was not significantly different according to Gleason grade (P=0.893). These results were not changed when confined to the patients with PSA between 2.5 and 10.0 ng/mL (P=0.654 and P=0.672, respectively). In addition, there was no significant difference in the risk of PCa at different cut-off values of NKA.ConclusionThese results indicate that NKA does not appear to be very useful for detection of PCa and prediction of Gleason grade. Further large multi-institutional studies are required to verify the role of NKA in PCa detection and Gleason grade prediction.

Abstract 227: Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Abstract We performed an in-depth and well-powered investigation of genetic variation across the cancer susceptibility region at chromosome 8q24 (127.6-129.0 Mb) to search for novel risk variants associated with prostate cancer (PCa) risk in the European ancestry population. We combined genotyped and imputed data from the PRACTICAL/ELLIPSE OncoArray and iCOGS consortia consisting of 71,535 PrCa cases and 52,935 controls of European ancestry. Variants with high imputation quality score (>0.8) were retained for a total of 5,600 overlapping variants between the two datasets. Associations of genetic variants with PCa risk were evaluated using unconditional logistic regression with adjustment for country and ten principal components. The marginal risk estimates for the 5,600 variants that passed quality control were combined by a fixed effects meta-analysis. A meta-stepwise selection was performed on variants marginally associated with PCa risk from the meta results (P<0.05). A polygenic risk score and the contribution to the familial relative risk of PCa were estimated for variants from the final model. Of the 5,600 variants at 8q24 retained for analysis, 1,268 (23%) were associated with PCa risk at P<5x10-8 while 2,772 (49%) were marginally associated at P<0.05. In the stepwise model, 12 variants remained statistically significantly associated with PCa risk with conditional meta p-values between 2.93x10-137 and 4.28x10-15. The independent stepwise signals were confirmed by Joint Analysis of Marginal (JAM) summary statistics, which defined the credible sets of variants driving those signals. Three of the variants (rs1914295, rs190257175, rs12549761) were weakly correlated (r2≤0.17) with any known PCa risk marker, and may define novel association signals. Men in the top 1% of the polygenic risk score distribution had a 3.97-fold relative risk (95%CI=3.87-4.07) compared to men with "average risk" (25th-75th percentiles). The 12 independent signals at 8q24 capture 11.54% (95%CI=9.86-13.65) of the familial relative risk of PCa, which is approximately one quarter of the total PCa familial relative risk explained by known genetic risk factors. Most of the independently associated signals have good evidence for biologic functionality; in particular, many reside within putative transcriptional enhancers and/or binding sites for AR and FOXA1 transcription factors in prostate cell lines. In summary, we defined 12 independent association signals among men of European ancestry, with three of the risk variants representing putative novel association signals. Whereas the individual associations of these variants with PCa risk are relatively modest (ORs<2.0), their cumulative effects are substantial, and their contribution to the overall familial relative risk of PCa is substantially greater than any other known prostate cancer risk locus. Citation Format: Marco Matejcic, Edward J. Saunders, Tokhir Dadaev, Mark Brook, Ali Amin Al Olama, Fredrick R. Schumacher, Sonja I. Berndt, Sara Benlloch, Kenneth Muir, Koveela Govindasami, Victoria L. Stevens, Susan M. Gapstur, Catherine M. Tangen, Jyotsna Batra, Judith Clements, APCB (Australian Prostate Cancer Bio Resource), Henrik Gronberg, Nora Pashayan, Johanna Schleutker, Demetrius Albanes, Alicja Wolk, Catharine West, Lorelei Mucci, Peter Kraft, Géraldine Cancel-Tassin, Stella Koutros, Karina Dalsgaard Sorensen, Lovise Maehle, Eli Marie Grindedal, Sara Strom, David E. Neal, Freddie C. Hamdy, Jenny L. Donovan, Ruth C. Travis, Robert J. Hamilton, Sue Ann Ingles, Barry Rosenstein, Yong-Jie Lu, Graham G. Giles, Adam S. Kibel, Ana Vega, Jeanette Bensen, Manolis Kogevinas, Fredrik Wiklund, Stephen Chanock, Douglas F. Easton, Rosalind A. Eeles, Zsofia Kote-Jarai, David V. Conti, Christopher A. Haiman. Germline variation at 8q24 and prostate cancer risk in men of European ancestry [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 227.

Difference in prostate cancer incidence around sixty years: effects of age and metabolic diseases.

We examined the risk of prostate cancer in the Korean population stratified on the basis of age group and risk based on metabolic diseases, using National Health Insurance System (NHIS) data. Of the 51,827,813 people from the NHIS data in 2015, 10,879,591 men without prostate cancer who underwent a health examination were analyzed. The risk of prostate cancer was analyzed with stratification by age. Multivariate‐adjusted Cox regression analysis was conducted to examine the association between prostate cancer and metabolic diseases by age groups. The risk of prostate cancer increased continuously with age and 59 years may be a point of inflection. The hazard ratio (HR) of prostate cancer development rose sharply as that age point passed. The population with metabolic diseases was more likely to develop prostate cancer than the population without any of these components. In addition, the incidence rate ratio (IRR) decreased from the youngest age group to the age group comprising 55–59 year olds. Beyond this age group, there was a plateau. The relative risk for prostate cancer associated with metabolic diseases also showed divergent associations with age. The risk of prostate cancer increased continuously with age and the peak Youden index was at 59 years. The relative risk for prostate cancer according to metabolic diseases also showed divergent associations beyond 59 years of age. Therefore, setting the age threshold at 59 years would improve the present clinical risk stratification for prostate cancer in Korea.

Adherence to Mediterranean diet and risk of prostate cancer

In Europe, countries following the traditional Mediterranean Diet (MeDi), particularly Southern European countries, have lower prostate cancer (PCa) incidence and mortality compared to other European regions. In the present study, we investigated the association between the MeDi and the relative risk of PCa and tumor aggressiveness in a Spanish population. Among individual score components, it has been found that subjects with PCa were less likely to consume olive oil as the main culinary fat, vegetables, fruits and fish than those without. However, these differences were not statistically significative. A high intake of fruit, vegetables and cooked tomato sauce Mediterranean style (sofrito) was related to less PCa aggressiveness. Results showed that there are no differences in the score of adherence to the Mediterranean dietary patterns between cases and controls, with mean values of 8.37 ± 1.80 and 8.25 ± 2.48, respectively. However, MeDi was associated with lower PCa agressiveness according to Gleason score. Hence, relations between Mediterranean dietary patterns and PCa are still inconclusive and merit further investigations. Further large-scale studies are required to clarify the effect of MeDi on prostate health, in order to establish the role of this diet in the prevention of PCa.

A study of prostate cancer and its association with dyslipidemia, elevated insulin levels in blood, and relative insulin resistance prevalent in South East Asia

Background and Objectives: Prostate cancer is the second most common cause of cancer and the sixth leading cause of cancer death among men worldwide. In India, it is the second most common cancer in males as per the Indian Council of Medical Research and various state cancer registries. This study was designed to investigate the effect of dyslipidemia, elevated insulin levels, and insulin resistance on the risk of prostate cancer. Materials and Methods: This case–control study was conducted on a total of 200 individuals. Cases were 100 males under the age of 80 (range, 50–80 years), newly diagnosed with histologically confirmed primary adenocarcinoma of the prostate. Controls were 100 age-matched disease-free males, without any complications. Mean ± standard deviation in case and control groups was compared using the unpaired Student's t-test. Pearson's correlation analysis was used to determine the association between variables of interest and prostate-specific antigen (PSA), Homeostasis Model Assessment-Insulin Resistance (HOMA-IR), and body mass index (BMI) among prostate cancer patients. Unadjusted and adjusted odd ratios with 95% CI were calculated using logistic regression models for prostate cancer risk in relation to dyslipidemia and IR. Results: Data showed that serum PSA significantly positively associated with BMI, total cholesterol, triglycerides (TGs), low-density lipoprotein-cholesterol (LDL-C), insulin, HOMA-IR and significantly negatively associated with high-density lipoprotein-cholesterol (HDL-C). HOMA-IR significantly positively associated with BMI, TGs, glucose, and insulin. The binary logistic regression analysis showed a significant adjusted* Odds Ratio (OR) with 95% confidence interval (P

Prostate-Specific Antigen Increase during Dutasteride to Indicate the Need for Prostate Biopsy: Influence of Prostatic Inflammation

The aim of this study was to analyze the significance of an increase in total prostate-specific antigen (PSA) serum levels despite dutasteride treatment as a predictor of prostate cancer (PC) at biopsy. We focused our attention on the rate of the first PSA increase and on the influence of prostatic inflammation. From 2011 to 2016, 365 men with a previous negative prostate biopsy and persistent elevated PSA levels received dutasteride treatment. The population was followed for a range of 12-48 months. One hundred twelve cases with a confirmed PSA increase >0.5 ng/ml over the nadir value during the follow-up were included in Group A and underwent a new prostate biopsy. In Group A, the PSA increase was associated with PC at the re-biopsy in 66% of cases. The percentage of PSA reduction after 6 months of treatment was not a significant indicator of the risk for PC. The distribution of inflammatory infiltrates significantly (p<00.01) varied from positive to negative prostate biopsies. The relative risk for PC at biopsy significantly increased according to PSA level during dutasteride. Treatment with dutasteride can help to analyze PSA kinetic. A persistent prostatic inflammation is a factor able to reduce the performance of PSA kinetic during dutasteride treatment.

P007 - Prostate cancer risk in relation to Insulin-like Growth Factor-1, IGF-Binding Protein-3 and Body Mass Index

P007 - Prostate cancer risk in relation to Insulin-like Growth Factor-1, IGF-Binding Protein-3 and Body Mass Index

Common cancers share familial susceptibility: implications for cancer genetics and counselling

BackgroundIt has been proposed that cancer is more common in some families than in others, but the hypothesis lacks population level support. We use a novel approach by studying any...

Prostate Cancer Risk in Relation to CYP3A4 and CYP3A5 Genotypes in the Bangladeshi Population

Genetic polymorphism on CYP3A4 and CYP3A5 gene and their associational susceptibility to prostate cancer was studied on Bangladeshi population, considering the importance of CYP3A4 and CYP3A5 gene in detoxification of xenobiotics from physiological territory. In this case control regulated study, we focused on two allelic variants CYP3A4 rs2740574 (CYP3A4*1B) and CYP3A5 rs776746 (CYP3A5*3) applying Polymerase Chain Reaction (PCR)-Restriction Fragment Length Polymorphism (RFLP). Associational risk on prostate cancer was estimated as odds ratio (OR) and 95% confidence interval (CI) using unconditional logistic regression models. An elevated prostate cancer risk was found with heterozygous, mutant and heterozygous plus mutant variants of CYP3A4*1B which is not statistically significant (p&gt;0.05), whereas a significant association was found with heterozygous, mutant and heterozygous plus mutant variants of CYP3A5*3 (OR =4.36, 95%CI = 1.53 to 12.38, P =0.003; OR =3.85, 95%CI = 1.19 to 12.43, P = 0.017 and OR =4.13, 95%CI = 1.84 to 9.28, p =0.0006 respectively). The findings signposted a significant association of CYP3A5*3 gene and nullify the association of CYP3A4*1B gene’s polymorphism with prostate cancer risk in Bangladeshi subject.Dhaka Univ. J. Pharm. Sci. 14(2): 179-185, 2015 (December)

Worldwide Prevalence of Human Papillomavirus and Relative Risk of Prostate Cancer: A Meta-analysis.

Despite the increasing number of studies conducted recently to evaluate the association between HPV infections and the risk of prostate cancer, the results remain inconclusive. Furthermore, the prevalence and distribution of overall and individual HPV types worldwide in prostate cancer has not been reported until now. Therefore, we estimated the prevalence of HPV in prostate cancer by pooling data of 46 studies with 4919 prostate cancer cases, taking into account the heterogeneity of major related parameters, including study region, specimen type, HPV DNA source, detection method, publication calendar period and Gleason score. Moreover, we tested the association of HPV infections with prostate cancer risks by a meta-analysis of 26 tissue-based case-control studies. We found that the prevalence of HPV infection was 18.93% (95% CI = 17.84–20.05%) in prostate cancer cases, and most of which were high-risk HPV types (17.73%, 95% CI = 16.52–18.99%). The prevalence varied by region, PCR primers used, publication calendar period and Gleason score. Our study also showed a significantly increased risk of prostate cancer with the positivity of overall HPV detected in prostate tissues (OR = 1.79, 95% CI = 1.29–2.49) and revealed the geographic variation of association strength (P < 0.001). In conclusion, HPV infections may contribute to the risk of prostate cancer.

Physical Activity from Early Adulthood and Risk of Prostate Cancer: A 24-Year Follow-Up Study among Icelandic Men.

Physical activity in adult life may reduce prostate cancer risk. Data are scarce on the role of activity during early adulthood, as well as combined recreational and occupational physical activity on prostate cancer risk and mortality. We undertook a prospective study of 8,221 Icelandic men (born 1907 to 1935) in the population-based Reykjavik Study. At enrollment, between 1967 and 1987, the men provided information on regular recreational physical activity since the age of 20 years as well as current occupational activity. Through linkage to nationwide cancer and mortality registers, the men were followed for prostate cancer diagnosis and mortality through 2009. We used Cox models to calculate the relative risk of prostate cancer by level of physical activity. During a mean follow-up of 24.8 years, 1,052 men were diagnosed with prostate cancer, of whom 349 had advanced disease (stage 3+ or prostate cancer death). Neither recreational nor occupational physical activity was, independently or combined, associated with overall or localized prostate cancer. Compared with physically inactive men, we observed a nonsignificant lower risk of advanced prostate cancer [HR, 0.67; 95% confidence interval (CI), 0.42-1.07] among men reporting both recreational and occupational physical activities (P value for interaction = 0.03). Awaiting confirmation in larger studies with detailed assessment of physical activity, our data suggest that extensive physical activity beginning in early adulthood may reduce the risk of advanced prostate cancer.

Abstract 3449: Risk for death from prostate cancer predicted from complete family history of lethal prostate cancer

Abstract Background: Familial relative risks (RR) for death from prostate cancer (lethal prostate cancer or LPC) are rare. Most risk estimations are for diagnosis of prostate cancer (PC); and typically focus on close relatives, rather than on complete family history. This study provides RRs for LPC based on specific family history data of LPC obtained from a statewide Cancer Registry linked to genealogy data. The risk estimates presented avoid common recall, recruitment, and ascertainment biases, and provide more individualized risk estimates. Methods: We used a population-based resource to estimate RRs for LPC based on a full constellation of family history of LPC. We include complete family history, taking into account degree of relationship (first to third-degree), age at diagnosis, paternal or maternal family history, number of affected individuals, and age at diagnosis of youngest relative. Estimations of RR for LPC based on specific family history are informative for patients and clinicians for appropriate screening decisions. The Utah Population Data Base (UPDB), a computerized population genealogical resource linked to a statewide SEER cancer registry, and statewide death certificates was analyzed. Over 1 million individuals were analyzed. All males with specific constellations of LPC were identified in the UPDB (probands) and the observed number of LPC cases among these probands was compared to the expected number using internal cohort-specific rates to obtain RR estimates. Results: Over 3,921 LPC cases were identified. Risk for LPC was significantly elevated with each additional LPC first-degree relative (FDR), ranging from RR = 2.26 (95% CI: 2.09, 2.44) for &amp;gt;0 FDRs to RR = 3.93 (1.69, 7.73) for &amp;gt;2 FDRs affected. Even in the absence of FDR family history, significantly increased risk for LPC was observed in the presence of &amp;gt;0 second degree relatives (SDR) affected (RR = 1.53: 1.41, 1.66). In the absence of affected FDRs and SDRs, there was significantly increased risk for LPC for &amp;gt;1 third degree relative (TDR) affected (RR = 1.22: 1.15, 1.29). Results indicated higher risks for maternal vs paternal history, e.g. RR = 1.50 (1.27, 1.76) for affected paternal uncle versus RR = 1.83 (1.59, 2.09) for affected maternal uncle. Discussion: RRs for LPC have more clinical significance than RRs for PC. This study provides unbiased, population-based estimates of LPC risk based on a man's specific family history LPC constellation. Many individuals at 2-3 times increased risk for dying from PC were identified based on family history. This study provides a means for containing healthcare costs and conserving resource utilization through informed use of familial LPC risks. Using informative LPC family history in the planning of screening, treatment, and monitoring opens additional avenues for implementation of more sound translational medicine practices, decreasing morbidity and mortality, and improving the quality of life in patients. Citation Format: Frederick S. Albright, Neeraj Agarwal, William T. Lowrance, Robert A. Stephenson, Lisa A. Cannon-Albright. Risk for death from prostate cancer predicted from complete family history of lethal prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3449. doi:10.1158/1538-7445.AM2015-3449

PROSTATE CANCER AND HEREDITARY SYNDROMES

The aim of this study is to assess relative risk of prostate cancer (PC) and other tumors in families of patients with multiple primary malignancies (MPM) and the syndrome of hereditary nonpolyposis colorectal cancer (HNPCC). The study is based on data from the cancer register of families that includes information on 560 patients with MPM, 126 families with HNPCC and their first-degree relatives. Incidence of these diseases in population served as the control. Among 560 probands with PPN 217 (38.7%) were male and 343 (61.3%) – female. Only 12 (2.1%) male patients had tumor in the prostate. In these patients 24 tumors were identified. Two patients had synchronous tumors, other ten patients had metachronous. Eight patients with prostate cancer had tumors of other organs: 5 – in rectum, 2 – in colon and 1 – in bladder. As a second tumor prostate cancer was diagnosed in 4 patients, three of them had rectal cancer and one – colon cancer. Only 2 (0.3%) patients had prostate cancer as a primary tumor. Clinical and genealogical information achieved from 543 patients with MPM, including in 206 male probands. Among 3637 first-degree relatives of probands with MPM prostate cancer was diagnosed in 2 (0.11 ±2.3%) patients that was 1.7 times higher than in population (0.063±0.0019%). The relative risk of prostate cancer for relatives of patients from families with HNPCC syndrome was 0.8 ± 6.3% that was 12/7 times higher than in the control group (p <0.05). The estimation of the relative risk in families of male probands was perfprmed. Among 1460 male relatives with MPM only 1 (0.14%) case of prostate cancer was diagnosed (son of proband). Among 42 families of male probands with HNPCC syndrome, prostate cancer was detected in 2 (1.3%) brothers that exceeds population risk 20.6 times. Although the molecular mechanisms and pathogenesis of prostate cancer in such families is unknown, its association with a HNPCC-syndrome and possibly MPM-syndrome is obvious. Higher relative risk of developing prostate cancer for male relatives of probands with MPM and HNPCC syndrome presupposes inherited genetically determined predisposition to disease development. Further molecular and genetic studies are needed to determine the genetic basis of predisposition to prostate cancer in these families.