Use of hospital big data to optimize and personalize laboratory test interpretation with an application.

BACKGROUND AND AIMS: In laboratory medicine, test results are generally interpreted with 95% reference intervals but correlations between laboratory tests are usually ignored. We aimed to use hospital big data to optimize and personalize laboratory data interpretation, focusing on platelet count. MATERIAL AND METHODS: Laboratory tests were extracted from the hospital database and exploited by an algorithmic stepwise procedure. For any given laboratory test Y, an "optimized and personalized reference population" was defined by keeping only patients whose laboratory values for all Y-correlated tests fell within their own usual reference intervals, and by partitioning groups by individual-specific variables like sex and age category. The method was applied to platelet count. RESULTS: Laboratory data were recorded for 28,082 individuals. At the end of the algorithmic process, seven correlated laboratory tests were chosen, resulting in a reference sample of 159 platelet counts. A new 95 % reference interval was constructed [152-334 × 109/L], notably reduced (27.2 %) compared to conventional reference values [150-400 × 109/L]. The reference interval was validated on a sample of 2,129 patients from another downtown laboratory, emphasizing the potential transference of the hospital-derived reference limits. CONCLUSION: This method offers new perspectives in laboratory data interpretation, especially in patient screening and longitudinal follow-up.

Circulating Biomarkers Predictive of Treatment Response in Patients with Hormone-sensitive or Castration-resistant Metastatic Prostate Cancer: A Systematic Review.

BACKGROUND AND OBJECTIVE: Metastatic prostate cancer (mPCa) harbors genomic alterations that may predict targeted therapy efficacy. These alterations can be identified not only in tissue but also directly in biologic fluids (ie, liquid biopsies), mainly blood. Liquid biopsies may represent a safer and less invasive alternative for monitoring patients treated for mPCa. Current research focuses on the description and validation of novel predictive biomarkers to improve precision medicine in mPCa. Our aim was to systematically review the current evidence on liquid biopsy biomarkers for predicting treatment response in mPCa. METHODS: We systematically searched Medline, Web of Science, and evidence-based websites for publications on circulating biomarkers in mPCa between March 2013 and February 2024 for review. Endpoints were: prediction of overall survival, biochemical or radiographic progression-free survival after treatment (chemotherapy, androgen deprivation therapy, androgen receptor pathway inhibitors [ARPIs], immunotherapy, or PARP inhibitors [PARPIs]). For each biomarker, the level of evidence (LOE) for clinical validity was attributed: LOE IA and IB, high level of evidence; LOE IIB and IIC, intermediate level; and LOE IIIC and LOE IV-VD, weak level. KEY FINDINGS AND LIMITATIONS: The predictive value of each biomarker for the response to several therapies was evaluated in both metastatic hormone-sensitive (mHSPC) and castration-resistant prostate cancer (mCRPC). In patients with mCRPC, BRCA1/2 or ATM mutations predicted response to ARPIs (LOE IB) and PARPIs (LOE IIB), while AR-V7 transcripts or AR-V7 protein levels in circulating tumor cells (CTCs) predicted response to ARPIs and taxanes (LOE IB). CTC quantification predicted response to cabazitaxel, abiraterone, and radium-223 (LOE IIB), while TP53 alterations predicted response to 177Lu prostate-specific membrane antigen radioligand treatment (LOE IIB). AR copy number in circulating tumor DNA before the first treatment line and before subsequent lines predicted response to docetaxel, cabazitaxel, and ARPIs (LOE IIB). In mHSPC, DNA damage in lymphocytes was predictive of the response to radium-223 (LOE IIB). CONCLUSIONS AND CLINICAL IMPLICATIONS: BRCA1/2, ATM, and AR alterations detected in liquid biopsies may help clinicians in management of patients with mPCa. The other circulating biomarkers did not reach the LOE required for routine clinical use and should be validated in prospective independent studies. PATIENT SUMMARY: We reviewed studies assessing the value of biomarkers in blood or urine for management of metastatic prostate cancer. The evidence indicates that some biomarkers could help in selecting patients eligible for specific treatments.

Sexually and non-sexually transmitted infections and the risk of prostate cancer: Results from the EPICAP study.

INTRODUCTION: Prostate cancer (PCa) is by far the most common type of cancer among men in western countries. However, relatively little is known about its etiology despite the high morbidity and mortality. It has been suggested that chronic inflammation may be involved in prostate carcinogenesis. We investigated the role of sexually and non-sexually transmitted infections in prostate cancer risk with a specific interest in the aggressive types. METHODS: We used data from epidemiological study of prostate cancer (EPICAP), a population-based case-control study. A total of 819 incident cases and 879 controls were interviewed face-to-face using a standardized questionnaire gathering information on known or suspected risk factors of prostate cancer and personal history of specific sexually and non-sexually transmitted infections: gonorrhea, syphilis, trichomonas, herpes, mononucleosis, Epstein-Barr virus, varicella-zoster, and dengue. Odds ratios (OR) and their 95% confidence interval were estimated using multivariate unconditional logistic regression. RESULTS: There was no significant association between gonorrhea (OR: 0.90, 95% CI: 0.61-1.33), trichomonas (OR: 0.74, 95% CI: 0.27-2.07), genital herpes (OR: 0.69, 95% CI: 0.38-1.27), and the risk of prostate cancer. No association emerged for overall sexually transmitted bacterial and viral infections (OR 1.05, 95% CI: 0.86-1.29) and overall non-sexually transmitted viral infections (OR 1.11, 95% CI: 0.90-1.35) and the risk of prostate cancer. CONCLUSION: Our results showed that sexually or non-sexually transmitted infections, either bacterial or viral, were not associated to prostate cancer. Therefore, further investigation is needed to help advance our understanding of the role of chronic inflammation in the etiology of prostate cancer, with a particular focus on its most aggressive types.

Circulating tumour cells and PD-L1-positive small extracellular vesicles: the liquid biopsy combination for prognostic information in patients with metastatic non-small cell lung cancer.

BACKGROUND: Circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), and extracellular vesicles (EVs) are minimally invasive liquid biopsy biomarkers. This study investigated whether they predict prognosis, alone or in combination, in heterogenous unbiased non-small cell lung cancer (NSCLC) patients. METHODS: Plasma samples of 54 advanced NSCLC patients from a prospective clinical trial. CtDNA mutations were identified using the UltraSEEK™ Lung Panel (MassARRAY® technology). PD-L1 expression was assessed in small EVs (sEVs) using an enzyme-linked immunosorbent assay. RESULTS: At least one ctDNA mutation was detected in 37% of patients. Mutations were not correlated with overall survival (OS) (HR = 1.1, 95% CI = 0.55; 1.83, P = 0.980) and progression-free survival (PFS) (HR = 1.00, 95% CI = 0.57-1.76, P = 0.991). High PD-L1+ sEV concentration was correlated with OS (HR = 1.14, 95% CI = 1.03-1.26, P = 0.016), but not with PFS (HR = 1.08, 95% CI = 0.99-1.18, P = 0.095). The interaction analysis suggested that PD-L1+ sEV correlation with PFS changed in function of CTC presence/absence (P interaction = 0.036). The combination analysis highlighted worse prognosis for patients with CTCs and high PD-L1+ sEV concentration (HR = 7.65, 95% CI = 3.11-18.83, P < 0.001). The mutational statuses of ctDNA and tumour tissue were significantly correlated (P = 0.0001). CONCLUSION: CTCs and high PD-L1+ sEV concentration correlated with PFS and OS, but not ctDNA mutations. Their combined analysis may help to identify patients with worse OS. TRIAL REGISTRATION: NCT02866149, Registered 01 June 2015, https://clinicaltrials.gov/ct2/show/study/NCT02866149 .

Conversation between a clinical biologist and an artificial intelligence on prostate cancer biomarkers: a critical reading.

Artificial intelligence is increasingly used in the field of medicine as a diagnostic aid, particularly for image analysis and more generally for data processing. Many artificial intelligence-based tools have been specifically developed for clinical biology, but some more general ones can help to improve the dissemination of medical knowledge. To test whether and to what extent an automated conversation tool could answer questions on a clinical biology topic (i.e. prostate cancer biomarkers), we questioned ChatGPT, an artificial intelligence-powered model dedicated to optimize language models for dialogue. Then we analyzed its responses.

Detection and Monitoring of Tumor-Derived Mutations in Circulating Tumor DNA Using the UltraSEEK Lung Panel on the MassARRAY System in Metastatic Non-Small Cell Lung Cancer Patients.

Analysis of circulating tumor DNA (ctDNA) is a potential minimally invasive molecular tool to guide treatment decision-making and disease monitoring. A suitable diagnostic-grade platform is required for the detection of tumor-specific mutations with high sensitivity in the circulating cell-free DNA (ccfDNA) of cancer patients. In this multicenter study, the ccfDNA of 72 patients treated for advanced-stage non-small cell lung cancer (NSCLC) was evaluated using the UltraSEEK® Lung Panel on the MassARRAY® System, covering 73 hotspot mutations in EGFR, KRAS, BRAF, ERBB2, and PIK3CA against mutation-specific droplet digital PCR (ddPCR) and routine tumor tissue NGS. Variant detection accuracy at primary diagnosis and during disease progression, and ctDNA dynamics as a marker of treatment efficacy, were analyzed. A multicenter evaluation using reference material demonstrated an overall detection rate of over 90% for variant allele frequencies (VAFs) > 0.5%, irrespective of ccfDNA input. A comparison of UltraSEEK® and ddPCR analyses revealed a 90% concordance. An 80% concordance between therapeutically targetable mutations detected in tumor tissue NGS and ccfDNA UltraSEEK® analysis at baseline was observed. Nine of 84 (11%) tumor tissue mutations were not covered by UltraSEEK®. A decrease in ctDNA levels at 4-6 weeks after treatment initiation detected with UltraSEEK® correlated with prolonged median PFS (46 vs. 6 weeks; p < 0.05) and OS (145 vs. 30 weeks; p < 0.01). Using plasma-derived ccfDNA, the UltraSEEK® Lung Panel with a mid-density set of the most common predictive markers for NSCLC is an alternative tool to detect mutations both at diagnosis and during disease progression and to monitor treatment response.

[Immuno-analytical characteristics of PSA and derived biomarkers (total PSA, free PSA, p2PSA)]. / Caractéristiques immuno-analytiques du PSA et des biomarqueurs dérivés (PSA total, PSA libre et P2ProPSA).

Prostate-specific antigen (PSA) is the recommended tumor marker for individual screening and follow-up of prostate cancer. This paper reviews main structural and physiological data about prostate specific antigen isoforms: total PSA, free PSA, [-2]proPSA (also named p2PSA). It describes the pre-, per- and post-analytical conditions for these different parameters. It presents the interpretation of results and derived calculated indices (free/total PSA ratio, Prostate Health Index or PHI) for the management of prostate cancer (initial diagnosis and follow-up).

Urinary biomarkers for bladder cancer diagnosis and NMIBC follow-up: a systematic review.

BACKGROUND: Bladder cancer detection and follow-up is based on cystoscopy and/or cytology, but it remains imperfect and invasive. Current research focuses on diagnostic biomarkers that could improve bladder cancer detection and follow-up by discriminating patients at risk of aggressive cancer who need confirmatory TURBT (Transurethral Resection of Bladder Tumour) from patients at no risk of aggressive cancer who could be spared from useless explorations. OBJECTIVE: To perform a systematic review of data on the clinical validity and clinical utility of eleven urinary biomarkers (VisioCyt®, Xpert®Bladder, BTA stat®, BTA TRAK™, NMP22 BC®, NMP22® BladderChek® Test, ImmunoCyt™/uCyt1+™, UroVysion Bladder Cancer Kit®, Cxbladder, ADXBLADDER, Urodiag®) for bladder cancer diagnosis and for non-muscle invasive bladder cancer (NMIBC) follow-up. METHODS: All available studies on the 11 biomarkers published between May 2010 and March 2021 and present in MEDLINE® were reviewed. The main endpoints were clinical performance for bladder cancer detection, recurrence or progression during NMIBC monitoring, and additional value compared to cytology and/or cystoscopy. RESULTS: Most studies on urinary biomarkers had a prospective design and high level of evidence. However, their results should be interpreted with caution given the heterogeneity among studies. Most of the biomarkers under study displayed higher detection sensitivity compared with cytology, but lower specificity. Some biomarkers may have clinical utility for NMIBC surveillance in patients with negative or equivocal cystoscopy or negative or atypical urinary cytology findings, and also for recurrence prediction. CONCLUSION: Urinary biomarkers might have a complementary place in bladder cancer diagnosis and NMIBC surveillance. However, their clinical benefit remains to be confirmed.

HE4 and CA-125 kinetics to predict outcome in patients with recurrent epithelial ovarian carcinoma: the META4 clinical trial.

HE4 and CA-125 are used for epithelial ovarian cancer (EOC) screening, diagnosis, and follow-up. Our objective was to study HE4 and CA-125 kinetics in patients treated for recurrent EOC. Serum samples were prospectively collected before the first chemotherapy cycle and every 3 months until disease progression. Data from 89/101 patients could be analyzed. At baseline, the median CA-125 and HE4 concentrations were 210 IU/L (7-10,310) and 184 pM (31-4,836). Among the 12 patients (13%) with normal CA-125 (<35 IU/L) concentration, eight had HE4 concentration ≥75 pM, and among the 16 patients with normal HE4 concentration (18%), 12 had increased CA-125 concentration. The median nadir concentrations were 31 IU/L (3-8,744) for CA-125 and 75 pM (20-4,836) for HE4. The median times to nadir were 14 (0-130) weeks for CA-125 and 12 (0-52) weeks for HE4. In multivariate analysis, CA-125 and HE4 nadir concentrations (<35 IU/L, HR 0.35, 95% CI: 0.17-0.72 and<75 pM, HR 0.40, 95% CI: 0.20-0.79) and time to CA-125 and HE4 nadir (>14 weeks, HR 0.37, 95% CI: 0.20-0.70 and >12 weeks, HR 0.43, 95% CI: 0.23-0.83) were prognostic factors of progression-free survival. More investigations on HE4 kinetics could help to better monitor patients with CA-125 concentration within normal values.

Diabetes, metabolic syndrome and prostate cancer risk: Results from the EPICAP case-control study.

BACKGROUND: Diabetes may be associated with decreased prostate cancer (PCa) risk. However, previous studies have not always accounted for time since diabetes diagnosis or antidiabetic drug use. Futhermore, the role of metabolic syndrome (MetS) in PCa risk is still debated. We investigated the role of diabetes and MetS in PCa risk based on data from the Epidemiological study of PCa (EPICAP). METHODS: EPICAP is a population-based case-control study that included 819 incident PCa cases in 2012-2013 and 879 controls frequency matched by age. MetS was characterized according to National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III). Logistic regression models adjusted for age, family history of PCa and ethnicity, were used to assess odds ratios (ORs) and their 95%conficence intervals (CIs) for the associations between diabetes, MetS and PCa risk. RESULTS: Whereas we did not observed an association between diabetes and PCa, a decreased risk of PCa has been highlighted with an increasing treated diabetes duration (p-trend=0.008). No association has been observed between MetS, the number of MetS criteria and the risk of PCa. However, we suggested that NSAIDs use could modify the association between MetS and PCa risk. CONCLUSION: Our results suggest an inverse association between the duration of diabetes and PCa risk. The role of metabolic factors, such as MetS and its components, in PCa risk remains unclear and requires further investigations.

Sleep Patterns and Risk of Prostate Cancer: A Population-Based Case Control Study in France (EPICAP).

BACKGROUND: Sleep disturbances have been singled out for their implication in the risk of several cancer sites. However, results for prostate cancer are still inconsistent. METHODS: We used data from the EPICAP study, a French population-based case-control study including 819 incident prostate cancer cases and 879 controls frequency matched by age. Detailed information on sleep duration on work/free days, and sleep medication over lifetime was collected. RESULTS: Sleep duration and sleep deprivation were not associated with prostate cancer, whatever the aggressiveness of prostate cancer. However, sleep deprivation was associated with an increased prostate cancer risk among men with an evening chronotype [OR, 1.96; 95% confidence interval (CI), 1.04-3.70]. We also observed an increased risk of prostate cancer with higher duration of sleep medication use (Ptrend = 0.008). This association with long duration of sleep medication use (≥10 years) was more pronounced among men who worked at night 15 years or more (OR, 3.84; 95% CI, 1.30-11.4) and among nonusers of NSAID (OR, 2.08; 95% CI, 1.15-3.75). CONCLUSIONS: Our results suggested that chronotype, night work, or NSAID use could modify the association between sleep disorders and prostate cancer occurrence needing further investigations to go further. IMPACT: EPICAP is the first study, which investigates several sleep indicators taking into account potential effect modifiers. If our findings were confirmed, we could identify subgroups of men at higher risk of prostate cancer that may be accessible to preventive measures.

Occupation and prostate Cancer risk: results from the epidemiological study of prostate cancer (EPICAP).

BACKGROUND: Although prostate cancer (PCa) is the most frequent male cancer in industrialized countries, little is known about its aetiology. The literature has suggested an influence of the environment, including occupational exposures, but results are inconsistent. In this context, we investigated PCa risk associated to employment among several occupations using data from EPICAP study. METHODS: EPICAP is a French population-based case-control study including 819 PCa incident cases and 879 controls frequency-matched on age. In-person interviews gathered data on potential risk factors and lifetime occupational histories for each job held at least 6 months. Then, occupations were coded using ISCO 68. Unconditional logistic regressions were performed to assess the association between occupations (ever occupied and by duration) and PCa risk, whether all and aggressive, after adjusting for potential confounders. RESULTS: For ≥10 years of employment, we found positive associations with PCa, whether overall and aggressive, among Medical, Dental and Veterinary workers (OR (odds ratios) =5.01 [95% confidence interval] [1.27; 19.77]), Members of the armed forces (OR = 5.14 [0.99; 26.71]) and Fishermen, hunters and related workers (OR = 4.58 [1.33; 15.78]); whether overall and non-aggressive PCa, among Legislative officials and Government administrators (OR = 3.30 [1.10; 9.84]) or Managers (OR = 1.68 [1.18; 2.41]); however a negative association, whether overall and non-aggressive PCa, among Material-Handling and Related Equipment Operators, Dockers and Freight Handlers (OR = 0.40 [0.17; 0.97]). CONCLUSION: Excess PCa risks were observed in the EPICAP study mostly among white collar workers exposed to several factors in their work environment. These emerging associations can be used to lead future research investigating specific occupational exposures.

[Moving towards a personalized oncology: The contribution of genomic techniques and artificial intelligence in the use of circulating tumor biomarkers]. / En marche vers une oncologie personnalisée : l'apport des techniques génomiques et de l'intelligence artificielle dans l'usage des biomarqueurs tumoraux circulants.

Technological advances, in particular the development of high-throughput sequencing, have led to the emergence of a new generation of molecular biomarkers for tumors. These new tools have profoundly changed therapeutic management in oncology, with increasingly precise molecular characterization of tumors leading to increasingly personalized therapeutic targeting. Detection of circulating tumor cells and/or circulating tumor DNA in blood samples -so-called 'liquid biopsies'- can now provide a genetic snapshot of the patient's tumor through an alternative and less invasive procedure than biopsy of the tumor tissue itself. This procedure for characterizing and monitoring the disease in real time facilitates the search for possible relapses, the emergence of resistance, or emergence of a new therapeutic target. In the long term, it might also provide a means of early detection of cancer. These new approaches require the treatment of ever-increasing amounts of clinical data, notably, with the goal of calculating composite clinical-biological predictive scores. The use of artificial intelligence will be unavoidable in this domain, but it raises ethical questions and implications for the health-care system that will have to be addressed.

[Clinical use and evolution of circulating biomarkers in the era of personalized oncology: From protein markers to bioclinical scores]. / Utilisation clinique et évolution des biomarqueurs circulants à l'ère de l'oncologie personnalisée : des marqueurs protéiques aux scores clinicobiologiques.

In oncology, the identification of targets that correlate with a type of cancer has led to a profound change in the notion of "tumor markers". Technological advances, in particular the development of high-throughput sequencing, have led to the emergence of a new generation of molecular biomarkers for tumors. Despite their limited utility for screening and diagnosis, conventional tumor markers remain interesting for evaluation of prognoses, the choice and optimization of treatments, as well as for monitoring the effectiveness of those treatments. In this article, we revisit the conventional serum markers that are enjoying a 'come back' thanks to the development of high-performance scores based on biological, cytological, clinical, or radiological criteria.

Traumatic memory reactivation with or without propranolol for PTSD and comorbid MD symptoms: a randomised clinical trial.

Post-traumatic stress disorder (PTSD) is difficult to treat but one promising strategy is to block memory reconsolidation of the traumatic event. This study aimed to evaluate the efficacy of traumatic memory reactivation under the influence of propranolol, a noradrenergic beta-receptor blocker, in reducing PTSD symptoms as well as comorbid major depression (MD) symptoms. We conducted a double blind, placebo-controlled, randomised clinical trial in 66 adults diagnosed with longstanding PTSD. Propranolol or a placebo was administered 90 min before a brief memory reactivation session, once a week for 6 consecutive weeks. Measures included the SCID PTSD module, the PTSD Check List (PCL-S) and the Beck Depression Inventory-II (BDI-II). PTSD symptoms decreased both in the pre-reactivation propranolol group (39.28%) and the pre-reactivation placebo group (34.48 %). During the 6 treatment sessions, PCL-S and BDI-II scores decreased to similar extent in both groups and there were no treatment differences. During the 3-month follow-up period, there were no treatment effects for the mean PCL-S and BDI-II scores. However, in patients with severe PTSD symptoms (PCL-S ≥ 65) before treatment, PCL-S and BDI-II scores continued to decline 3 months after the end of treatment in the propranolol group while they increased in the placebo group. Repeated traumatic memory reactivation seemed to be effective for PTSD and comorbid MD symptoms. However, the efficacy of propranolol was not greater than that of placebo 1 week post treatment. Furthermore, in this traumatic memory reactivation, PTSD symptom severity at baseline might have influenced the post-treatment effect of propranolol.

Clinical practice guidelines for BRCA1 and BRCA2 genetic testing.

BRCA1 and BRCA2 gene pathogenic variants account for most hereditary breast cancer and are increasingly used to determine eligibility for PARP inhibitor (PARPi) therapy of BRCA-related cancer. Because issues of BRCA testing in clinical practice now overlap with both preventive and therapeutic management, updated and comprehensive practice guidelines for BRCA genotyping are needed. The integrative recommendations for BRCA testing presented here aim to (1) identify individuals who may benefit from genetic counselling and risk-reducing strategies; (2) update germline and tumour-testing indications for PARPi-approved therapies; (3) provide testing recommendations for personalised management of early and metastatic breast cancer; and (4) address the issues of rapid process and tumour analysis. An international group of experts, including geneticists, medical and surgical oncologists, pathologists, ethicists and patient representatives, was commissioned by the French Society of Predictive and Personalised Medicine (SFMPP). The group followed a methodology based on specific formal guidelines development, including (1) evaluating the likelihood of BRCAm from a combined systematic review of the literature, risk assessment models and expert quotations, and (2) therapeutic values of BRCAm status for PARPi therapy in BRCA-related cancer and for management of early and advanced breast cancer. These international guidelines may help clinicians comprehensively update and standardise BRCA testing practices.

Mass Spectrometry as a Highly Sensitive Method for Specific Circulating Tumor DNA Analysis in NSCLC: A Comparison Study.

Plasma-based tumor mutational profiling is arising as a reliable approach to detect primary and therapy-induced resistance mutations required for accurate treatment decision making. Here, we compared the FDA-approved Cobas® EGFR Mutation Test v2 with the UltraSEEK™ Lung Panel on the MassARRAY® System on detection of EGFR mutations, accompanied with preanalytical sample assessment using the novel Liquid IQ® Panel. 137 cancer patient-derived cell-free plasma samples were analyzed with the Cobas® and UltraSEEK™ tests. Liquid IQ® analysis was initially validated (n = 84) and used to determine ccfDNA input for all samples. Subsequently, Liquid IQ® results were applied to harmonize ccfDNA input for the Cobas® and UltraSEEK™ tests for 63 NSCLC patients. The overall concordance between the Cobas® and UltraSEEK™ tests was 86%. The Cobas® test detected more EGFR exon19 deletions and L858R mutations, while the UltraSEEK™ test detected more T790M mutations. A 100% concordance in both the clinical (n = 137) and harmonized (n = 63) cohorts was observed when >10 ng of ccfDNA was used as determined by the Liquid IQ® Panel. The Cobas® and UltraSEEK™ tests showed similar sensitivity in EGFR mutation detection, particularly when ccfDNA input was sufficient. It is recommended to preanalytically determine the ccfDNA concentration accurately to ensure sufficient input for reliable interpretation and treatment decision making.

Body mass index trajectories and prostate cancer risk: Results from the EPICAP study.

Elevated body mass index (BMI) has been inconsistently associated with prostate cancer occurrence but it has been suggested that life course adulthood obesity may be associated with an increased risk of prostate cancer. However, few studies have investigated lifetime BMI and prostate cancer risk. We analyzed life course BMI trajectories on prostate cancer risk based on data from the Epidemiological study of Prostate Cancer (EPICAP). We included in our analyses 781 incident prostate cancer cases and 829 controls frequency matched by age. Participants were asked about their weight every decade from age 20 to two years before reference date. BMI trajectories were determined using group-based trajectory modeling to identify groups of men with similar patterns of BMI changes. We identified five BMI trajectories groups. Men with a normal BMI at age 20 developing overweight or obesity during adulthood were at increased risk of aggressive prostate cancer compared to men who maintained a normal BMI. Our results suggest that BMI trajectories resulting in overweight or obesity during adulthood are associated with an increased risk of aggressive prostate cancer, particularly in never smokers, emphasizing the importance of maintaining a healthy BMI throughout adulthood.

Circadian genes polymorphisms, night work and prostate cancer risk: Findings from the EPICAP study.

Over the past two decades, several studies have attempted to understand the hypothesis that disrupting the circadian rhythm may promote the development of cancer. Some have suggested that night work and some circadian genes polymorphisms are associated with cancer, including prostate cancer. Our study aims to test the hypothesis that prostate cancer risk among night workers may be modulated by genetic polymorphisms in the circadian pathway genes based on data from the EPICAP study, a population-based case-control study including 1511 men (732 cases/779 controls) with genotyped data. We estimated odds ratio (ORs) and P values of the association between prostate cancer and circadian gene variants using logistic regression models. We tested the interaction between circadian genes variants and night work indicators that were significantly associated with prostate cancer at pathway, gene and SNP levels. Analyses were also stratified by each of these night work indicators and by cancer aggressiveness. The circadian pathway was significantly associated with aggressive prostate cancer among night workers (P = .004), particularly for men who worked at night for <20 years (P = .0002) and those who performed long night shift (>10 hours, P = .001). At the gene level, we observed among night workers significant associations between aggressive prostate cancer and ARNTL, NPAS2 and RORA. At the SNP-level, no significant association was observed. Our findings provide some clues of a potential modulating effect of circadian genes in the relationship between night work and prostate cancer. Further investigation is warranted to confirm these findings and to better elucidate the biological pathways involved.