scholarly journals Redefining the Bladder Cancer Phenotype using Patterns of Familial Risk

2019 ◽  
Author(s):  
Heidi A. Hanson ◽  
Claire L. Leiser ◽  
Christopher Martin ◽  
Sumati Gupta ◽  
Ken R. Smith ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Clustering Analysis ◽  
Cox Regression ◽  
Familial Risk ◽  
Population Database ◽  
Familial Data ◽  
Increased Risk ◽  
New Directions ◽  
Cancer Types ◽  
Cancer Phenotype

AbstractRelatives of bladder cancer (BCa) patients have been shown to be at increased risk for kidney, lung, thyroid, and cervical cancer after correcting for smoking related behaviors that may concentrate in some families. We demonstrate a new method to simultaneously assess risks for multiple cancers to identify distinct multi-cancer configurations (multiple different cancer types that cluster in relatives) surrounding BCa patients. We identified 6,416 individuals with urothelial carcinoma and familial information using the Utah Cancer Registry and Utah Population Database (UPDB). First-degree relatives, second-degree relatives, and first cousins were used to construct a familial enrichment matrix for cancer-types previously shown to be individually associated with BCa. K-medioids clustering were used to identify Familial Multi-Cancer Configurations (FMC). A case-control design and Cox regression with a 1:5 ratio of BCa cases to cancer-free controls was used to quantify the risk in specific relative-types and spouses in each FMC. Clustering analysis revealed 12 distinct FMCs, each exhibiting a different pattern of cancer co-aggregation. Of the 12 FMCs, four exhibited strong familial risk of bladder cancer along with specific patterns of increased risk of cancers in other sites (BCa FMCs), and were the focus of further investigation. Cancers at increased risk in these four BCa FMCs most commonly included melanoma, prostate and breast cancer and less commonly included leukemia, lung, pancreas and kidney cancer. A network-based approach can be used with familial data to discover new phenotype clusters for BCa, providing new directions for discovering patterns of cancer clustering.

scholarly journals MRI phenotypes of the brain are related to future stroke and mortality in patients with manifest arterial disease: The SMART-MR study

2018 ◽  
Vol 40 (2) ◽  
pp. 354-364 ◽  
Author(s):  
Myriam G Jaarsma-Coes ◽  
Rashid Ghaznawi ◽  
Jeroen Hendrikse ◽  
Cornelis Slump ◽  
Theo D Witkamp ◽  
...  
Keyword(s):  
Clustering Analysis ◽  
Cox Regression ◽  
Reference Group ◽  
Brain Mri ◽  
Arterial Disease ◽  
Brain Abnormalities ◽  
Accurate Representation ◽  
Increased Risk ◽  
The Brain ◽  
Mr Study

Neurodegenerative and neurovascular diseases lead to heterogeneous brain abnormalities. A combined analysis of these abnormalities by phenotypes of the brain might give a more accurate representation of the underlying aetiology. We aimed to identify different MRI phenotypes of the brain and assessed the risk of future stroke and mortality within these subgroups. In 1003 patients (59 ± 10 years) from the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART-MR) study, different quantitative 1.5T brain MRI markers were used in a hierarchical clustering analysis to identify 11 distinct subgroups with a different distribution in brain MRI markers and cardiovascular risk factors, and a different risk of stroke (Cox regression: from no increased risk compared to the reference group with relatively few brain abnormalities to HR = 10.34; 95% CI 3.80↔28.12 for the multi-burden subgroup) and mortality (from no increased risk compared to the reference group to HR = 4.00; 95% CI 2.50↔6.40 for the multi-burden subgroup). In conclusion, within a group of patients with manifest arterial disease, we showed that different MRI phenotypes of the brain can be identified and that these were associated with different risks of future stroke and mortality. These MRI phenotypes can possibly classify individual patients and assess their risk of future stroke and mortality.

scholarly journals A population-wide analysis of the familial risk of suicide in Utah, USA

2021 ◽  
pp. 1-10
Author(s):  
Amanda V. Bakian ◽  
Danli Chen ◽  
Chong Zhang ◽  
Heidi A. Hanson ◽  
Anna R. Docherty ◽  
...  
Keyword(s):  
Suicide Risk ◽  
Cox Regression ◽  
Familial Risk ◽  
Risk Groups ◽  
Population Based ◽  
Unified Framework ◽  
Population Database ◽  
First Degree Relatives ◽  
Hazard Ratios ◽  
History Of

Abstract Background The degree to which suicide risk aggregates in US families is unknown. The authors aimed to determine the familial risk of suicide in Utah, and tested whether familial risk varies based on the characteristics of the suicides and their relatives. Methods A population-based sample of 12 160 suicides from 1904 to 2014 were identified from the Utah Population Database and matched 1:5 to controls based on sex and age using at-risk sampling. All first through third- and fifth-degree relatives of suicide probands and controls were identified (N = 13 480 122). The familial risk of suicide was estimated based on hazard ratios (HR) from an unsupervised Cox regression model in a unified framework. Moderation by sex of the proband or relative and age of the proband at time of suicide (<25 v. ⩾25 years) was examined. Results Significantly elevated HRs were observed in first- (HR 3.45; 95% CI 3.12–3.82) through fifth-degree relatives (HR 1.07; 95% CI 1.02–1.12) of suicide probands. Among first-degree relatives of female suicide probands, the HR of suicide was 6.99 (95% CI 3.99–12.25) in mothers, 6.39 in sisters (95% CI 3.78–10.82), and 5.65 (95% CI 3.38–9.44) in daughters. The HR in first-degree relatives of suicide probands under 25 years at death was 4.29 (95% CI 3.49–5.26). Conclusions Elevated familial suicide risk in relatives of female and younger suicide probands suggests that there are unique risk groups to which prevention efforts should be directed – namely suicidal young adults and women with a strong family history of suicide.

scholarly journals 1389Do associations between a healthy lifestyle and incidence of cancer differ by genetic risk?

2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Stephanie Byrne ◽  
Terry Boyle ◽  
Beben Benyamin ◽  
Sang Hong Lee ◽  
Muktar Ahmed ◽  
...  
Keyword(s):  
Cancer Risk ◽  
Cancer Incidence ◽  
Genetic Risk ◽  
Cox Regression ◽  
Healthy Lifestyle ◽  
Lymphocytic Leukemia ◽  
European Ancestry ◽  
Risk Scores ◽  
Increased Risk ◽  
Cancer Types

Abstract Background It is unknown whether relationships between lifestyle and cancer differ by genetic risk. We investigated this for 13 cancer types using prospective data from the UK Biobank. Methods In 2006-2010, participants aged 37-73 years completed an assessment and provided biological samples. Those of European ancestry with no history of malignant cancer were included in our analysis (n = 196,485). For each individual, a healthy lifestyle index (HLI) was calculated based on recommendations, and polygenic risk scores (PRSs) were computed for 13 cancer types. Relationships with cancer incidence were assessed by cox regression, adjusting for age, sex, assessment centre, birth location, and measures of socioeconomic status. Interactions between the HLI and PRSs were explored. Results For all cancer outcomes, a high genetic risk was associated with an increased cancer risk, or there was a trend in that direction. Those in the top PRS tertile had a greater than 2-fold increased risk of colorectal cancer (HR[95%CI]=2.18[1.90,2.49]), pancreatic cancer (2.39[1.71,3.32]) and lymphocytic leukemia (2.45[1.67,3.59]). An unhealthy lifestyle was associated with a higher cancer risk for 8 cancer types, with strong relationships observed for lung (3.41[2.76,4.20]), pancreatic (2.06[1.47,2.91]), bladder (1.95[1.43,2.66]) and kidney cancers (1.90[1.43,2.54]). No interactions between HLI and PRSs were detected (all interaction p-values&gt;0.10). Conclusions Associations between lifestyle and cancer incidence did not differ by genetic risk. Key messages A healthy lifestyle can reduce the risk of several cancers, even in those who are genetically predisposed to develop cancer.

Risk of solid cancers overall and by subtypes in patients with psoriatic arthritis treated with TNF inhibitors – a Nordic cohort study

Rheumatology ◽  
2021 ◽  
Author(s):  
Karin Hellgren ◽  
Christine Ballegaard ◽  
Bénédicte Delcoigne ◽  
René Cordtz ◽  
Dan Nordström ◽  
...  
Keyword(s):  
Cohort Study ◽  
Psoriatic Arthritis ◽  
Cox Regression ◽  
Tnf Inhibitors ◽  
Solid Cancer ◽  
Increased Risk ◽  
National Patient ◽  
Large Cohort Study ◽  
Cancer Types ◽  
Estimate Hazard Ratio

Abstract Objectives To investigate whether TNF inhibitors (TNFi) are associated with increased risk of solid cancer in patients with psoriatic arthritis (PsA). Methods From the Nordic clinical rheumatology registers (CRR) here: SRQ/ARTIS (Sweden), DANBIO (Denmark), NOR-DMARD (Norway), ROB-FIN (Finland) and ICEBIO (Iceland) we identified PsA patients who started a first TNFi 2001–2017 (n = 9655). We identified patients with PsA not treated with biologics from (i) the CRR (n = 14 809) and (ii) the national patient registers (PR, n = 31 350). By linkage to the national cancer registers, we collected information on incident solid cancer overall and for eight cancer types. We used Cox regression to estimate hazard ratio (HR) with 95% CI of cancer (per country and pooled) in TNFi-exposed vs biologics-naïve, adjusting for age, sex, calendar period, comorbidities and disease activity. We also assessed standardized incidence ratios (SIR) in TNFi-exposed PsA vs the general population (GP). Results We identified 296 solid cancers among the TNFi-exposed PsA patients (55 850 person-years); the pooled adjusted HR for solid cancer overall was 1.0 (0.9–1.2) for TNFi-exposed vs biologics-naïve PsA from the CRR, and 0.8 (0.7–1.0) vs biologics-naïve PsA from the PRs. There were no significantly increased risks for any of the cancer types under study. The pooled SIR of solid cancer overall in TNFi treated PsA vs GP was 1.0 (0.9–1.1). Conclusion In this large cohort study from five Nordic countries, we found no increased risk of solid cancer in TNFi-treated PsA patients, neither for solid cancer overall nor for eight common cancer types.

scholarly journals Extended Mortality Follow-up of a Cohort of 25,460 Workers Exposed to Acrylonitrile

2019 ◽  
Vol 188 (8) ◽  
pp. 1484-1492 ◽  
Author(s):  
Stella Koutros ◽  
Jay H Lubin ◽  
Barry I Graubard ◽  
Aaron Blair ◽  
Patricia A Stewart ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Proportional Hazards ◽  
Cox Regression ◽  
The United States ◽  
Cox Proportional Hazards ◽  
Sensitivity Analyses ◽  
Increased Risk ◽  
Total Cancer ◽  
Standardized Mortality Ratios

Abstract We extended the mortality follow-up of a cohort of 25,460 workers employed at 8 acrylonitrile (AN)-producing facilities in the United States by 21 years. Using 8,124 deaths and 1,023,922 person-years of follow-up, we evaluated the relationship between occupational AN exposure and death. Standardized mortality ratios (SMRs) based on deaths through December 31, 2011, were calculated. Work histories and monitoring data were used to develop quantitative estimates of AN exposure. Hazard ratios were estimated by Cox proportional hazards regression. All-cause mortality and death from total cancer were less than expected compared with the US population. We observed an excess of death due to mesothelioma (SMR = 2.24, 95% confidence interval (CI): 1.39, 3.42); no other SMRs were elevated overall. Cox regression analyses revealed an elevated risk of lung and bronchial cancer (n = 808 deaths; for >12.1 ppm-year vs. unexposed, hazard ratio (HR) = 1.43, 95% CI: 1.13, 1.81; P for trend = 0.05), lagged 10 years, that was robust in sensitivity analyses adjusted for smoking and co-exposures including asbestos. Death resulting from bladder cancer (for >2.56 ppm vs. unexposed, lagged 10-year HR = 2.96, 95% CI: 1.38, 6.34; P for trend = 0.02) and pneumonitis (for >3.12 ppm-year vs. unexposed, HR = 4.73, 95% CI: 1.42, 15.76; P for trend = 0.007) was also associated with AN exposure. We provide additional evidence of an association between AN exposure and lung cancer, as well as possible increased risk for death due to bladder cancer and pneumonitis.

scholarly journals CCL2 is associated with metastasis and poor prognosis of bladder cancer

2019 ◽  
Author(s):  
wei gao ◽  
qiwang zhang ◽  
lianhua zhang ◽  
qiang liu ◽  
xuehui duan ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Regression Models ◽  
Cox Regression ◽  
Tumor Grade ◽  
The Novel ◽  
Kaplan Meier ◽  
Ccl2 Expression ◽  
Immune Factor ◽  
Cancer Types

Abstract Background: Chemokine (C-C motif) ligand 2 (CCL2) is an important immune factor, which may be important in cancer progression by promoting proliferation, invasion metastasis and the tumor microenvironment. Recent researches have demonstrated that overexpression of CCL2 is associated with unfavorable prognosis in various cancer types. In this study, we aim to determine the prognostic value of CCL2 expression in patients with bladder cancer (BC). Methods: We retrospectively enrolled 154 patients with bladder cancer at Renji Hospital, Shanghai Jiaotong University between 2005 and 2007. CCL2 expression was assessed by immunohistochemical staining and its association with clinicopathologic features and prognosis were evaluated. Kaplan-Meier method was applied to compare survival curves. Cox regression models were fitted to analyze the effect of prognostic factors on Overall survival (OS). Results: CCL2 protein had high expression in 73 of 154 cases of BC (47%). CCL2 overexpression was significantly associated with tumor grade (P<0.001), stage (P=0.005), and lymph node metastasis (P=0.025). The Kaplan–Meier survival analysis demonstrated that CCL2 expression was significantly associated with DSS and OS (both P< 0.001). Multivariate analysis further demonstrated that CCL2 was an independent prognostic factor for patients with BC. Conclusion: CCL2 might be a new molecular marker to predict the prognosis of patients with BC. The novel risk classification based on combining CCL2 and TNM is more reliable than using either alone.

scholarly journals MP06-15 REDEFINING THE BLADDER CANCER PHENOTYPE USING PATTERNS OF FAMILIAL RISK

2018 ◽  
Vol 199 (4S) ◽  
Author(s):  
Heidi Hanson ◽  
Claire Leiser ◽  
Christopher Martin ◽  
Brock O'Neil ◽  
William Lowrance ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Familial Risk ◽  
Cancer Phenotype

Lymphovascular Invasion Is Independently Associated With Overall Survival, Cause-Specific Survival, and Local and Distant Recurrence in Patients With Negative Lymph Nodes at Radical Cystectomy

2005 ◽  
Vol 23 (27) ◽  
pp. 6533-6539 ◽  
Author(s):  
Yair Lotan ◽  
Amit Gupta ◽  
Shahrokh F. Shariat ◽  
Ganesh S. Palapattu ◽  
Amnon Vazina ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Lymph Nodes ◽  
Lymphovascular Invasion ◽  
Cox Regression ◽  
Independent Predictor ◽  
Transitional Cell ◽  
Node Negative ◽  
Node Positive ◽  
Increased Risk

Purpose We hypothesized that bladder cancer patients with associated lymphovascular invasion (LVI) are at increased risk of occult metastases. Methods A multi-institutional group (University of Texas Southwestern [Dallas, TX], Baylor College of Medicine [Houston, TX], Johns Hopkins University [Baltimore, MD]) carried out a retrospective study of 958 patients who underwent cystectomy for bladder cancer between 1984 and 2003. Of patients with transitional-cell carcinoma (n = 776), LVI status was available for 750. LVI was defined as the presence of tumor cells within an endothelium-lined space. Results LVI was present in 36.4% (273 of 750) overall, involving 26% (151 of 581) and 72% (122 of 169) of node-negative and node-positive patients, respectively. Prevalence of LVI increased with higher pathologic stage (9.0%, 23%, 60%, and 78%, for T1, T2, T3, and T4, respectively; P < .001). Using multivariate Cox regression analyses including age, stage, grade, and number of pelvic lymph nodes removed, LVI was an independent predictor of local (HR = 2.03, P = .049), distant (HR = 2.60, P = .0011), and overall (HR = 2.02, P = .0003) recurrence in node-negative patients. LVI was an independent predictor of overall (HR = 1.84, P = .0002) and cause-specific (HR = 2.07, P = .0012) survival in node-negative patients. LVI maintained its independent predictor status in competing risks regression models (P = .013), where other-cause mortality was considered as a competing risk. LVI was not a predictor of recurrence or survival in node-positive patients. Conclusion LVI is an independent predictor of recurrence and decreased cause-specific and overall survival in patients who undergo cystectomy for invasive bladder cancer and are node-negative. These patients represent a high risk group that may benefit from integrated therapy with cystectomy and perioperative systemic chemotherapy.

scholarly journals The impact of hormones and reproductive factors on the risk of bladder cancer in women: results from the Nurses’ Health Study and Nurses’ Health Study II

2020 ◽  
Vol 49 (2) ◽  
pp. 599-607 ◽  
Author(s):  
Mohammad Abufaraj ◽  
Shahrokh Shariat ◽  
Marco Moschini ◽  
Florian Rohrer ◽  
Kyriaki Papantoniou ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cox Regression ◽  
Reproductive Factors ◽  
Gender Disparity ◽  
Health Study ◽  
Large Female ◽  
Age At Menarche ◽  
Age At Menopause ◽  
Increased Risk ◽  
The Impact

Abstract Background With three out of four new bladder cancer (BCa) cases occurring in men, an apparent gender disparity exists. We aimed to investigate the role of hormonal and reproductive factors in BCa risk using two large female US prospective cohorts. Methods Our study population comprised 118 256 and 115 383 female registered nurses who were recruited in the Nurses' Health Study (NHS) and NHS II, respectively. Reproductive and hormonal factors and other relevant data were recorded in biennial self-administered questionnaires. Cox-regression analyses were performed to estimate age- and multivariable-adjusted incidence risk ratios (IRRs) and 95% confidence intervals (CIs). Inverse-variance-weighted meta-analysis was used to pool estimates across cohorts. Results During up to 36 years of follow-up, 629 incident BCa cases were confirmed. In the NHS, 22 566 women (21.3%) were postmenopausal at baseline, compared with 2723 women (2.4%) in the NHS II. Among women in the NHS, younger age at menopause (≤45 years) was associated with an increased risk of BCa (IRR: 1.41, 95% CI: 1.11–1.81, Ptrend = 0.01) compared with those with menopause onset at age 50+ years, particularly among ever-smokers (IRR for age at menopause ≤45 years: 1.53, 95% CI: 1.15–2.04; PIntx = 0.16). Age at menarche and first birth, parity, oral-contraceptive use and postmenopausal hormone use were not associated with BCa risk. Conclusions Overall, we found little support for an association between female reproductive factors and BCa risk in these prospective cohort studies. Earlier age at menopause was associated with a higher risk of BCa, particularly among smokers, indicating the potential for residual confounding.

scholarly journals Cumulative incidence of midline incisional hernia and its surgical treatment after radical cystectomy and urinary diversion for bladder cancer: A nation-wide population-based study

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246703
Author(s):  
Fredrik Liedberg ◽  
Oskar Hagberg ◽  
Firas Aljabery ◽  
Truls Gårdmark ◽  
Staffan Jahnson ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Surgical Treatment ◽  
Incisional Hernia ◽  
Urinary Diversion ◽  
Cumulative Incidence ◽  
Cox Regression ◽  
Wound Dehiscence ◽  
Postoperative Wound ◽  
Cancer Data ◽  
Increased Risk

Background and objective To study the cumulative incidence and surgical treatment of midline incisional hernia (MIH) after cystectomy for bladder cancer. Methods In the nationwide Bladder Cancer Data Base Sweden (BladderBaSe), cystectomy was performed in 5646 individuals. Cumulative incidence MIH and surgery for MIH were investigated in relation to age, gender, comorbidity, previous laparotomy and/or inguinal hernia repair, operative technique, primary/secondary cystectomy, postoperative wound dehiscence, year of surgery, and period-specific mean annual hospital cystectomy volume (PSMAV). Results Three years after cystectomy the cumulative incidence of MIH and surgery for MIH was 8% and 4%, respectively. The cumulative incidence MIH was 12%, 9% and 7% in patients having urinary diversion with continent cutaneous pouch, orthotopic neobladder and ileal conduit. Patients with postoperative wound dehiscence had a higher three-year cumulative incidence MIH (20%) compared to 8% without. The corresponding cumulative incidence surgery for MIH three years after cystectomy was 9%, 6%, and 4% for continent cutaneous, neobladder, and conduit diversion, respectively, and 11% for individuals with postoperative wound dehiscence (vs 4% without). Using multivariable Cox regression, secondary cystectomy (HR 1.3 (1.0–1.7)), continent cutaneous diversion (HR 1.9 (1.1–2.4)), robot-assisted cystectomy (HR 1.8 (1–3.2)), wound dehiscence (HR 3.0 (2.0–4.7)), cystectomy in hospitals with PSMAV 10–25 (HR 1.4 (1.0–1.9)), as well as cystectomy during later years (HRs 2.5–3.1) were all independently associated with increased risk of MIH. Conclusions The cumulative incidence of MIH was 8% three years postoperatively, and increase over time. Avoiding postoperative wound dehiscence after midline closure is important to decrease the risk of MIH.

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