Impact of putative chemopreventative agents on prostate cancer diagnosis.

40 Background: Prostate cancer (PC) is the most common non-cutaneous cancer in Canadian men and the third most common cause of cancer death in Canada. Several studies have shown that use of commonly prescribed medications, including those used for diabetes and hypercholesterolemia, is associated with improved survival in various malignancies, including PC. There has not been any large population-based study, examining the effects of these and other commonly prescribed medications, on the rate of PC diagnosis, over a 20 years follow-up period. Methods: A retrospective population-based study using data from the institute of clinical evaluative sciences, including all male patients aged 65 and above in Ontario who have had a negative first prostate biopsy between 1994 and 2016. We assessed the impact of commonly prescribed medications on PC diagnosis. The medications included Statins (hydrophilic and hydrophobic), diabetes drugs (metformin, insulins, sulfonylureas, and thizolidinedions), proton pump inhibitors, 5 alpha reductase inhibitors, and alpha blockers. Time dependent Cox regression proportional hazards models were performed determine predictors of PC diagnosis. Medication exposure was time varying and modeled as “ever” vs. “never” use or as cumulative exposure for 6 months of usage. A priori variables included in the model included age, ADG comorbidity score, rurality index, index year, and all medications. Results: A total of 51,415 men were analyzed over a mean (SD) follow-up time of 8.06 (5.44) years. Overall, 10,466 patients (20.4%) were diagnosed with PC, 16,726 (32.5%) had died, and 1,460 (2.8%) patients died of PC. On multivariable analysis increasing age and rurality index were associated with higher PC diagnosis rate, while a more recent index year, and usage of hydrophilic statins was associated with a lower diagnosis rate in both “ever” vs. “never” and cumulative models (HR 0.832, 95% CI 0.732-0.946, p = 0.005, HR 0.973 95% CI 0.951-0.995, p = 0.016, respectively). Conclusions: Hydrophilic statins are associated with a clinically significant lower PC diagnosis. To our knowledge this is the first study demonstrating a clear advantage of one group of statins (hydrophilic) over another (hydrophobic) in PC prevention.

Download Full-text

IMPACT of putative chemopreventative agents on prostate cancer diagnosis.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e16553 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e16553-e16553

Author(s):

Hanan Goldberg ◽

Faizan Moshin ◽

Zachary William Abraham Klaassen ◽

Thenappan Chandrasekar ◽

Christopher J.D. Wallis ◽

...

Keyword(s):

Prostate Cancer ◽

Proportional Hazards ◽

Cox Regression ◽

Advanced Disease ◽

Large Population ◽

Multivariable Analysis ◽

Population Based ◽

Cumulative Exposure ◽

Population Based Study ◽

The Impact

e16553 Background: Prostate cancer (PC) is the most common non-cutaneous cancer in men and the third most common cause of cancer death in males. Several studies have shown that use of commonly prescribed medications, is associated with improved survival in various malignancies, including PC. There has not been any large population-based study, examining the effects of these and other commonly prescribed medications, such as proton pump inhibitors (PPI), on the rate of PC diagnosis, PC advanced disease and PC-specific death. Methods: A retrospective population-based study using data from the institute of clinical evaluative sciences, including all male patients aged 65 and above in Ontario who have had a negative first prostate biopsy between 1994 and 2016. We assessed the impact of commonly prescribed medications on PC outcomes. The analyzed medications included Statins (hydrophilic and hydrophobic), most commonly used diabetes drugs (metformin, insulins, sulfonylureas, and thizolidinedions), PPIs, 5 alpha reductase inhibitors, and alpha blockers. Time dependent Cox regression proportional hazards models were performed to determine predictors of PC diagnosis, PC advanced disease (defined as usage of hormonal therapy), and PC-specific death. Medication exposure was time varying and modelled as “ever” vs. “never” use or as cumulative exposure. Results: A total of 21,562 men were analyzed over a mean (SD) follow-up time of 8.06 (5.44) years. Overall, 5,187 patients (24%) were diagnosed with PC, 7861 (36.5%) had died, and 647 (3%) died of PC. On multivariable analysis usage of hydrophilic statins modelled as “ever vs. never” was associated with a lower diagnosis rate (OR 0.832, 95% CI 0.732-0.946, p = 0.005) and a significantly decreased PC-specific death (OR 0.676, 95% CI 0.528-0.871, p = 0.0024). In contrast, Pantoprazole was associated with a higher rate of advanced PC disease when modelled as cumulative exposure of 6 months (OR 1.03, 95% CI 1.003-1.06, P = 0.031), and PC-specific death, when modeled as “ever vs. never” (OR 1.26, 95% CI 1.02-1.576, p = 0.031). Conclusions: Hydrophilic statins were associated with a clinically and statistically significant lower PC diagnosis and PC-specific death, while pantoprazole was associated with a higher rate of advanced PC disease and PC-specific death.

Download Full-text

Prognostic Association between Common Laboratory Tests and Overall Survival in Elderly Men with De Novo Metastatic Castration Sensitive Prostate Cancer: A Population-Based Study in Canada

Cancers ◽

10.3390/cancers13112844 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2844

Author(s):

Christopher J. D. Wallis ◽

Bobby Shayegan ◽

Scott C. Morgan ◽

Robert J. Hamilton ◽

Ilias Cagiannos ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Clinical Decision Making ◽

Cox Regression ◽

De Novo ◽

Population Based ◽

Population Based Study ◽

Cox Regression Analysis ◽

Lymphocyte Ratio ◽

Laboratory Markers

De novo cases of metastatic prostate cancer (mCSPC) are associated with poorer prognosis. To assist in clinical decision-making, we aimed to determine the prognostic utility of commonly available laboratory-based markers with overall survival (OS). In a retrospective population-based study, a cohort of 3556 men aged ≥66 years diagnosed with de novo mCSPC between 2014 and 2019 was identified in Ontario (Canada) administrative database. OS was assessed by using the Kaplan–Meier method. Multivariate Cox regression analysis was performed to evaluate the association between laboratory markers and OS adjusting for patient and disease characteristics. Laboratory markers that were assessed include neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), albumin, hemoglobin, serum testosterone and PSA kinetics. Among the 3556 older men with de novo mCSPC, their median age was 77 years (IQR: 71–83). The median survival was 18 months (IQR: 10–31). In multivariate analysis, a statistically significant association with OS was observed with all the markers (NLR, PLR, albumin, hemoglobin, PSA decrease, reaching PSA nadir and a 50% PSA decline), except for testosterone levels. Our findings support the use of markers of systemic inflammation (NLR, PLR and albumin), hemoglobin and PSA metrics as prognostic indicators for OS in de novo mCSPC.

Download Full-text

Estimating the risk of developing secondary hematologic malignancies in patients with T1/T2 prostate cancer undergoing diverse treatment modalities: A large population‐based study

Cancer Medicine ◽

10.1002/cam4.4087 ◽

2021 ◽

Author(s):

Xiaofei Mo ◽

Mingge Zhou ◽

Hui Yan ◽

Xueqin Chen ◽

Yuetao Wang

Keyword(s):

Prostate Cancer ◽

Large Population ◽

Hematologic Malignancies ◽

Population Based ◽

Treatment Modalities ◽

Population Based Study

Download Full-text

Decreased serum TSH levels are not associated with mortality in the adult northeast German population

Acta Endocrinologica ◽

10.1530/eje-09-0566 ◽

2010 ◽

Vol 162 (3) ◽

pp. 579-585 ◽

Cited By ~ 39

Author(s):

Till Ittermann ◽

Robin Haring ◽

Sybille Sauer ◽

Henri Wallaschofski ◽

Marcus Dörr ◽

...

Keyword(s):

Cancer Mortality ◽

Cox Regression ◽

Large Population ◽

Population Based ◽

German Population ◽

Free Triiodothyronine ◽

Meta Analyses ◽

Serum Tsh ◽

Tsh Levels

ObjectiveResults of cohort studies on the association between decreased serum TSH levels and mortality are conflicting. Some studies demonstrated an increased mortality risk in subjects with decreased serum TSH levels, others did not. Even meta-analyses revealed contradictory results. We undertook the present study to investigate the association between decreased serum TSH levels and mortality in the large population-based Study of Health in Pomerania (SHIP).Design and methodsData from 3651 individuals from SHIP without known thyroid disorders or thyroid treatment were analyzed. Serum TSH, free triiodothyronine, and free thyroxine levels were determined by immunochemiluminescent procedures. Decreased TSH was defined as serum TSH levels below 0.25 mIU/l. Cox regression was used to associate decreased TSH levels with mortality.ResultsThe median duration of follow-up was 8.5 years (30 126 person years). During follow-up, 299 individuals (6.9%) died corresponding to a death rate of 9.92 deaths per 1000 person years. Survival time was shorter in subjects with decreased serum TSH levels compared to euthyroid individuals. After adjustment for age and sex, however, there was no association between decreased serum TSH levels and all-cause mortality (hazard ratio: 0.95; 95% confidence interval: 0.67; 1.36). Likewise, decreased serum TSH levels were neither associated with cardiovascular nor with cancer mortality.ConclusionsThere is no independent association of decreased serum TSH levels with all-cause, cardiovascular, and cancer mortality in the adult northeast German population. Although our study has some strengths, we cannot finally conclude on therapeutical implications in individuals with subclinical thyroid diseases.

Download Full-text

Risk of lung cancer in patients with gastro-esophageal reflux disease: a population-based cohort study

PeerJ ◽

10.7717/peerj.2753 ◽

2016 ◽

Vol 4 ◽

pp. e2753 ◽

Cited By ~ 4

Author(s):

Chi-Kuei Hsu ◽

Chih-Cheng Lai ◽

Kun Wang ◽

Likwang Chen

Keyword(s):

Lung Cancer ◽

Cohort Study ◽

Reflux Disease ◽

Cox Regression ◽

Large Population ◽

Population Based ◽

Chronic Obstructive ◽

Research Database ◽

Esophageal Reflux

This large-scale, controlled cohort study estimated the risks of lung cancer in patients with gastro-esophageal reflux disease (GERD) in Taiwan. We conducted this population-based study using data from the National Health Insurance Research Database of Taiwan during the period from 1997 to 2010. Patients with GERD were diagnosed using endoscopy, and controls were matched to patients with GERD at a ratio of 1:4. We identified 15,412 patients with GERD and 60,957 controls. Compared with the controls, the patients with GERD had higher rates of osteoporosis, diabetes mellitus, asthma, chronic obstructive pulmonary disease, pneumonia, bronchiectasis, depression, anxiety, hypertension, dyslipidemia, chronic liver disease, congestive heart failure, atrial fibrillation, stroke, chronic kidney disease, and coronary artery disease (all P < .05). A total of 85 patients had lung cancer among patients with GERD during the follow-up of 42,555 person-years, and the rate of lung cancer was 0.0020 per person-year. By contrast, 232 patients had lung cancer among patients without GERD during the follow-up of 175,319 person-years, and the rate of lung cancer was 0.0013 per person-year. By using stepwise Cox regression model, the overall incidence of lung cancer remained significantly higher in the patients with GERD than in the controls (hazard ratio, 1.53; 95% CI [1.19–1.98]). The cumulative incidence of lung cancer was higher in the patients with GERD than in the controls (P = .0012). In conclusion, our large population-based cohort study provides evidence that GERD may increase the risk of lung cancer in Asians.

Download Full-text

Seawater desalination and serum magnesium concentrations in Israel

Journal of Water and Health ◽

10.2166/wh.2016.164 ◽

2016 ◽

Vol 15 (2) ◽

pp. 296-299 ◽

Cited By ~ 7

Author(s):

Gideon Koren ◽

Meital Shlezinger ◽

Rachel Katz ◽

Varda Shalev ◽

Yona Amitai

Keyword(s):

Serum Magnesium ◽

Large Population ◽

Population Based ◽

Morbidity And Mortality ◽

Population Based Study ◽

Cardiac Morbidity ◽

Before And After ◽

The Mean ◽

Magnesium Status ◽

The Impact

With increasing shortage of fresh water globally, more countries are consuming desalinated seawater (DSW). In Israel >50% of drinking water is now derived from DSW. Desalination removes magnesium, and hypomagnesaemia has been associated with increased cardiac morbidity and mortality. Presently the impact of consuming DSW on body magnesium status has not been established. We quantified changes in serum magnesium in a large population based study (n = 66,764), before and after desalination in regions consuming DSW and in regions where DSW has not been used. In the communities that switched to DSW in 2013, the mean serum magnesium was 2.065 ± 0.19 mg/dl before desalination and fell to 2.057 ± 0.19 mg/dl thereafter (p < 0.0001). In these communities 1.62% of subjects exhibited serum magnesium concentrations ≤1.6 mg/dl between 2010 and 2013. This proportion increased by 24% between 2010–2013 and 2015–2016 to 2.01% (p = 0.0019). In contrast, no such changes were recorded in the communities that did not consume DSW. Due to the emerging evidence of increased cardiac morbidity and mortality associated with hypomagnesaemia, it is vital to consider re-introduction of magnesium to DSW.

Download Full-text

The effect of warfarin on the risk of prostate cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.14524 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 14524-14524

Author(s):

V. Tagalakis ◽

H. Tamim ◽

J. Collet ◽

S. R. Kahn ◽

M. Blostein ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Diagnosis ◽

Conditional Logistic Regression ◽

Oral Anticoagulants ◽

Large Population ◽

Population Based ◽

Cumulative Exposure ◽

Prolonged Treatment ◽

History Of ◽

Reduced Risk

14524 Background: The anticancer activity of oral anticoagulants has been a matter of debate for several years. Recent evidence suggests that prolonged treatment with warfarin may be associated with a reduced incidence of newly diagnosed urogenital cancer during long-term follow-up of patients with venous thromboembolism. The aim of this study was to assess whether exposure to warfarin was associated with reduced risk of prostate cancer in a large population-based cohort. Methods: We conducted a matched case-control study nested within the population of beneficiaries of the Saskatchewan Prescription Drug Plan aged 50 years and older from 1981–2002 with no history of cancer since 1967. New cases of prostate cancer diagnosed between 1981 and 2002 were identified using the linked Saskatchewan Cancer Agency registry. Six controls per case matched on age, gender, and sampling time were randomly selected. The cumulative exposure to warfarin in the five years preceding the cancer diagnosis was assessed. Prescription counts were used to define warfarin exposure. Exposure in the year immediately preceding the cancer diagnosis was excluded to control for detection bias. Conditional logistic regression analysis was used to assess confounding by other drugs such as nonsteroidal anti-inflammatory medications. Results: Among 11502 cases and 69012 controls, 7.4% of cases and 7.1% of controls had a history of any warfarin use. Compared to men who had never used warfarin, adjusted odds ratio (OR) for prostate cancer among ever-users in the 5 year period was 0.94 (95% confidence interval (CI), 0.86–1.03). In those who accumulated 1, 2, 3 and 4 years of warfarin use, the adjusted ORs were 1.01 (95% CI, 0.89–1.16), 1.00 (95% CI, 0.82–1.23), 0.81 (95% CI, 0.60–1.09), and 0.80 (95% CI, 0.65–0.99), respectively (p-trend=0.03). Conclusion: Our results suggest that cumulative use of warfarin of at least 4 years may be associated with a reduced risk of prostate cancer. However, confounding by other determinants of prostate cancer associated with warfarin use is possible. Nonetheless, confirmation of these findings by prospective studies may provide the evidence necessary to consider the use of warfarin in prostate cancer prevention. No significant financial relationships to disclose.

Download Full-text

Endogenous sex hormone levels in men are not associated with risk of venous thromboembolism: the Tromsø study

Acta Endocrinologica ◽

10.1530/eje-08-0888 ◽

2009 ◽

Vol 160 (5) ◽

pp. 833-838 ◽

Cited By ~ 19

Author(s):

Johan Svartberg ◽

Sigrid K Brækkan ◽

Gail A Laughlin ◽

John-Bjarne Hansen

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Free Testosterone ◽

Population Based ◽

Sex Hormone ◽

Population Based Study ◽

Hormone Levels ◽

Increased Risk ◽

The Impact

ObjectivesLow testosterone levels in men have been associated with cardiovascular risk factors and atherosclerosis and lately also an increased risk of both cardiovascular disease (CVD) and all-cause mortality. As arterial CVDs and venous thromboembolism (VTE) have been shown to share common risk factors, the purpose of the present study was to determine the impact of endogenous sex hormone levels on the incidence of VTE in a cohort of men.DesignA prospective, population-based study.MethodsSex hormone measurements were available in 1350 men, aged 50–84, participating in the Tromsø study in 1994–1995. First, lifetime VTE-events during the follow-up were registered up to September 1 2007.ResultsThere were 63 incident VTE-events (4.5 per 1000 person-years) during a mean of 10.4 years of follow-up. Age was significantly associated with increased risk of VTE; men 70 years or older had a 2.5-fold higher risk of VTE (HR 2.47, 95% CI 1.19–5.12), compared with those between 50 and 60 years of age. In age-adjusted analyses, endogenous sex hormones levels were not associated with risk of VTE; for each s.d. increase, hazards ratios (95% CI) were 1.06 (0.83–1.35) for total testosterone, 1.02 (0.79–1.33) for free testosterone, and 1.27 (0.94–1.71) for ln-estradiol. In dichotomized analyses comparing men in the lowest total and free testosterone quartile with men in the higher quartiles, hypoandrogenemia was not associated with risk of VTE.ConclusionsIn this population-based study of middle-aged and older men, endogenous sex hormone levels were not associated with 10-year risk of VTE.

Download Full-text