scholarly journals Prostate Cancer Mortality Associated with Aggregate Polymorphisms in Androgen-Regulating Genes: The Atherosclerosis Risk in the Communities (ARIC) Study

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1958
Author(s):  
Anna E. Prizment ◽  
Sean McSweeney ◽  
Nathan Pankratz ◽  
Corinne E. Joshu ◽  
Justin H. Hwang ◽  
...  

Genetic variations in androgen metabolism may influence prostate cancer (PC) prognosis. Clinical studies consistently linked PC prognosis with four single nucleotide polymorphisms (SNPs) in the critical androgen-regulating genes: 3-beta-hydroxysteroid dehydrogenase (HSD3B1) rs1047303, 5-alpha-reductase 2 (SRD5A2) rs523349, and solute carrier organic ion (SLCO2B1) rs1789693 and rs12422149. We tested the association of four androgen-regulating SNPs, individually and combined, with PC-specific mortality in the ARIC population-based prospective cohort. Men diagnosed with PC (N = 622; 79% White, 21% Black) were followed for death (N = 350) including PC death (N = 74). Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95%CI adjusting for center, age, stage, and grade at diagnosis using separate hazards for races. A priori genetic risk score (GRS) was created as the unweighted sum of risk alleles in the four pre-selected SNPs. The gain-of-function rs1047303C allele was associated PC-specific mortality among men with metastatic PC at diagnosis (HR = 4.89 per risk allele, p = 0.01). Higher GRS was associated with PC-specific mortality (per risk allele: HR = 1.26, p = 0.03). We confirmed that the gain-of-function allele in HSD3B1 rs1047303 is associated with greater PC mortality in men with metastatic disease. Additionally, our findings suggest a cumulative effect of androgen-regulating genes on PC-specific mortality; however, further validation is required.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2599-2599
Author(s):  
Susan Spillane ◽  
Kathleen Bennett ◽  
Linda Sharp ◽  
Thomas Ian Barron

2599 Background: Preclinical studies have suggested a role for metformin in the treatment of colorectal cancer (CRC). Associations between metformin versus sulfonylurea exposure and mortality (all-cause and colorectal cancer specific) are assessed in this population-based study of patients with a diagnosis of stage I-IV CRC. Methods: National Cancer Registry Ireland records were linked to prescription claims data and used to identify a cohort of patients with incident TNM stage I-IV CRC diagnosed 2001-2006. From this cohort, 2 patient groups were identified and compared for outcomes - those who received a prescription for metformin +/- a sulfonylurea (MET) or a prescription for sulfonylurea alone (SUL) in the 90 days pre CRC diagnosis. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox proportional hazards models adjusted for age, sex, stage, grade, site, comorbidities, year of diagnosis, and insulin, aspirin or statin exposure. Analyses were repeated stratifying by stage and site. Results: 5,617 patients with stage I-IV CRC were identified, of whom 369 received a prescription for metformin or a sulfonylurea in the 90 days pre diagnosis (median follow-up 1.6 years; MET: n=257; SUL: n=112). In adjusted analyses metformin exposure was associated with a 28% lower risk of all-cause mortality relative to sulfonylurea exposure (HR 0.72, 95% CI 0.53-0.98) and a non-significant 24% reduction in CRC-specific mortality (HR 0.76, 95% CI 0.52-1.13). In analyses stratified by site, in colon cancer, metformin exposure was associated with a significant one-third reduction in all-cause mortality (HR 0.66, 95% CI 0.46-0.95) and a non-significant reduction in site-specific mortality (HR 0.64, 95% CI 0.40-1.02). No mortality benefit was observed for rectal cancer. The association between metformin exposure and reduced mortality was strongest for stage I/II disease (all-cause mortality: HR 0.56, 95% CI 0.32-0.98; CRC-specific mortality: HR 0.48, 95% CI 0.21-1.11). Conclusions: Pre-diagnosis metformin exposure in CRC patients was associated with a significant reduction in mortality relative to sulfonylurea exposure. This benefit was greatest in patients with colon cancer and early stage disease.


2013 ◽  
Vol 141 (12) ◽  
pp. 2663-2670 ◽  
Author(s):  
S. D. CHUNG ◽  
Y. K. LIN ◽  
C. C. HUANG ◽  
H. C. LIN

SUMMARYThe relationship between sexually transmitted infections (STIs) and prostate cancer (PC) remains inconclusive. Moreover, all such studies to date have been conducted in Western populations. This study aimed to investigate the risk of PC following STI using a population-based matched-cohort design in Taiwan. The study cohort comprised 1055 patients with STIs, and 10 550 randomly selected subjects were used as a comparison cohort. Cox proportional hazards regression analysis revealed that the hazard ratio for PC during the 5-year follow-up period for patients with a STI was 1·95 (95% confidence interval 1·18–3·23), that of comparison subjects after adjusting for urbanization level, geographical region, monthly income, hypertension, diabetes, hyperlipidaemia, obesity, chronic prostatitis, history of vasectomy, tobacco use disorder, and alcohol abuse. We concluded that the risk of PC was higher for men who were diagnosed with a STI in an Asian population.


2020 ◽  
Vol 64 (4) ◽  
pp. 387-401
Author(s):  
M Anne Harris ◽  
Jill MacLeod ◽  
Joanne Kim ◽  
Manisha Pahwa ◽  
Michael Tjepkema ◽  
...  

Abstract Objectives Shift work with circadian disruption is a suspected human carcinogen. Additional population-representative human studies are needed and large population-based linkage cohorts have been explored as an option for surveillance shift work and cancer risk. This study uses a surveillance linkage cohort and job-exposure matrix to test relationships. Methods We estimated associations between shift work and breast, ovarian, and prostate cancer using the population-based Canadian Census Health and Environment Cohort (CanCHEC), linking the 1991 Canadian census to national cancer registry and mortality databases. Prevalence estimates from population labour survey data were used to estimate and assign probability of night, rotating, or evening shifts by occupation and industry. Cohort members were assigned to high (>50%), medium (>25 to 50%), low (>5 to 25%), or no (<5%) probability of exposure categories. Cox proportional hazards modelling was used to estimate associations between shift work exposure and incidence of prostate cancer in men and ovarian and breast cancer in women. Results The cohort included 1 098 935 men and 939 520 women. Hazard ratios (HRs) indicated null or inverse relationships comparing high probability to no exposure for prostate cancer: HR = 0.96, 95% confidence interval (CI) = 0.91–1.02; breast cancer: HR = 0.94, 95% CI = 0.90–0.99; and ovarian cancer: HR = 0.99, 95% CI = 0.87–1.13. Conclusions This study showed inverse and null associations between shift work exposure and incidence of prostate, breast, or ovarian cancer. However, we explore limitations of a surveillance cohort, including a possible healthy worker survivor effect and the possibility that this relationship may require the nuanced exposure detail in primary collection studies to be measurable.


2015 ◽  
Vol 49 (4) ◽  
pp. 402-408 ◽  
Author(s):  
Andrej Zist ◽  
Eitan Amir ◽  
Alberto F. Ocana ◽  
Bostjan Seruga

Abstract Background. Men with metastatic castrate-resistant prostate cancer (mCRPC) may not receive docetaxel in everyday clinical practice due to comorbidities. Here we explore the impact of comorbidity on outcome in men with mCRPC treated with docetaxel in a population-based outcome study. Methods. Men with mCRPC treated with docetaxel at the Institute of Oncology Ljubljana between 2005 and 2012 were eligible. Comorbidity was assessed by the age-adjusted Charlson comorbidity index (aa-CCI) and adult comorbidity evaluation (ACE-27) index. Hospital admissions due to the toxicity and deaths during treatment with docetaxel were used as a measure of tolerability. Association between comorbidity and overall survival (OS) was tested using the Cox proportional hazards analysis. Results. Two hundred and eight men were treated with docetaxel. No, mild, moderate and severe comorbidity was present in 2%, 32%, 53% and 13% using aa-CCI and in 27%, 35%, 29% and 8% when assessed by ACE-27. A substantial dose reduction of docetaxel occurred more often in men with moderate or severe comorbidity as compared to those with no or mild comorbidity. At all comorbidity levels about one-third of men required hospitalization or died during treatment with docetaxel. In univariate analysis a higher level of comorbidity was not associated with worse OS (aa-CCI HR 0.99; [95% CI 0.87–1.13], p = 0.93; ACE-27: HR 0.96; [95% CI 0.79–1.17], p = 0.69). Conclusions. Men with mCRPC, who have comorbidities may benefit from treatment with docetaxel.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4571-4571 ◽  
Author(s):  
D. V. Makarov ◽  
B. J. Trock ◽  
E. B. Humphreys ◽  
L. A. Mangold ◽  
M. A. Carducci ◽  
...  

4571 Background: For men developing PSA failure after radical prostatectomy (RP), administration of immediate androgen deprivation therapy (ADT) has not been shown to improve survival compared to delaying ADT until evidence of metastatic disease. We evaluated factors influencing prostate cancer (PCa) specific mortality (PCSM) in a cohort of PSA era patients developing metastases after RP treated with delayed ADT. Methods: 3,658 men had RP by a single surgeon at Johns Hopkins Hospital from 4/82 until 6/05. 553 had PSA failure. 216 developed radiographically evident distant metastasis. Of these, 91 men formed the study cohort: initially treated during the PSA era (1987–2005), received ADT only after documented metastasis, and having complete data. 41 of these men died. Median failure times were estimated with the Kaplan-Meier method. Prognostic impact was estimated as the hazard ratio (HR) derived from the Cox proportional hazards model. Results: Median followup from RP was 10 yrs (range 2–18). Actuarial median failure times are: 1 yr from RP to PSA failure (range 1–11), 32 mos from PSA failure to metastasis (range 0–129), 79 mos from metastasis to death (range 7–181), and 13 yrs from RP to death (range 2–18). The following variables were significant prognostic factors for PCSM in univariate analyses: Pain at diagnosis of metastases (p < 0.01), time from RP to metastasis (p = 0.02), hematocrit at metastasis (p < 0.01) and PSADT <3 mos during the 2 years prior to metastasis (p < 0.01). A multivariable Cox proportional hazards model demonstrated the following independent predictors of PCSM: pain (HR = 10.5 p < 0.01), PSA at metastasis ≥100 ng/mL (HR = 5.3 p < 0.01) and PSADT < 3 months (HR = 7.1 p < 0.01). PSADT determined in the two years immediately after PSA failure (HR = 1.0 p = 0.37) and time from RP to bone metastasis (HR = 1.0 p = 0.80) were not independent predictors of PCSM. Conclusion: Men receiving delayed ADT for development of metastasis after RP may have a prolonged survival time (13 yrs post RP - range 2–18). Optimizing the time for ADT in these patients requires well-designed, prospective randomized studies. Our data may facilitate the selection of patients and thresholds for implementation of ADT. No significant financial relationships to disclose.


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 9-9
Author(s):  
Shree Agrawal ◽  
Jason A. Efstathiou ◽  
Jeff M. Michalski ◽  
Thomas Michael Pisansky ◽  
Bridget F. Koontz ◽  
...  

9 Background: Early salvage radiation therapy (SRT) following radical prostatectomy (RP) has been shown to reduce biochemical recurrence and distant metastases. We aim to identify factors predictive of prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) from a consortium database from 10 academic institutions. Methods: 2,454 node-negative patients (pts) with detectable post-prostatectomy PSA ( ≥ 0.01 ng/mL) treated with SRT ± neoadjuvant/concurrent androgen deprivation therapy (N/C ADT) were included. Cumulative incidence and Kaplan-Meier methods were used to estimate rates of PCSM and ACM, respectively. Univariate and multivariable analyses (MVA) were performed by competing risks regression and Cox proportional hazards methods for PCSM and ACM. Results: Median follow-up was 5 years from SRT completion and 8 years from date of RP; 24% had pathologic Gleason score (GS) of ≤ 6, 56% GS 7, and 19% GS ≥ 8; 56% extraprostatic extension (EPE), 18% seminal vesicle invasion (SVI), 58% positive surgical margins, and 16% received N/C ADT. Median age at RP and SRT were 62 years (IQR 56-66) and 64 years (59-69), respectively. Median SRT dose was 66 Gy (IQR 65-68) and median pre-SRT PSA was 0.5 ng/mL (IQR 0.3-1.1). MVA performed from SRT completion date demonstrated higher pre-SRT PSA (HR = 2.1), higher GS (GS 7 vs. ≤ 6: HR 2.0; GS ≥ 8 vs. 6: HR 3.3) , SVI (HR 2.5), year of SRT (2000-2004, 1995-1999, 1985-1994 vs. 2005-2012; HR 2.9, HR 2.5, HR 3.6, respectively) were significantly associated with higher PCSM. These same variables were all significantly associated with higher PCSM and ACM rates calculated from both SRT completion date and date of RP. Conclusions: Initiation of early SRT at lower post-operative PSA levels following RP is associated with reduced risk of PCSM and ACM, even when calculated from RP date to account for lead time bias. Other factors significantly associated with PCSM include higher GS, SVI, and earlier year of SRT. [Table: see text]


2014 ◽  
Vol 22 (1) ◽  
pp. 77-85 ◽  
Author(s):  
Isabelle Laverdière ◽  
Christine Flageole ◽  
Étienne Audet-Walsh ◽  
Patrick Caron ◽  
Yves Fradet ◽  
...  

The prognostic significance of common deletions in uridine diphospho-glucuronosyltransferase 2B (UGT2B) genes encoding sex steroid metabolic enzymes has been recently recognized in localized prostate cancer (PCa) after radical prostatectomy (RP). However, the role of germline variations at theUGT1locus, encoding half of all human UGTs and primarily involved in estrogen metabolism, remains unexplored. We investigated whether variants ofUGT1are potential prognostic markers. We studied 526 Caucasian men who underwent RP for clinically localized PCa. Genotypes of patients for 34 haplotype-tagged single-nucleotide polymorphisms (htSNPs) and 11 additional SNPs across theUGT1locus previously reported to mark common variants including functional polymorphisms were determined. The risk of biochemical recurrence (BCR) was estimated using adjusted Cox proportional hazards regression and Kaplan–Meier analysis. We further investigated whether variants are associated with plasma hormone levels by mass spectrometry. In multivariable models, seven htSNPs were found to be significantly associated with BCR. A greater risk was revealed for fourUGT1intronic variants with hazard ratios (HRs) of 1.59–1.88 (P<0.002) for htSNPs inUGT1A10,UGT1A9, andUGT1A6. Conversely, decreased BCR was associated with three htSNPs in introns ofUGT1A10andUGT1A9(HR=0.56–058;P≤0.01). An unfavorableUGT1haplotype comprising all risk alleles, with a frequency of 14%, had a HR of 1.68 (95% CI=1.13–2.50;P=0.011). Significant alteration in circulating androsterone levels was associated with this haplotype, consistent with changes in hormonal exposure. This study provides the first evidence, to our knowledge, that germline polymorphisms ofUGT1are potential predictors of recurrence of PCa after prostatectomy.


2011 ◽  
Vol 165 (2) ◽  
pp. 209-215 ◽  
Author(s):  
Katarina Berinder ◽  
Olof Akre ◽  
Fredrik Granath ◽  
Anna-Lena Hulting

ObjectiveExperimental evidence indicates that prolactin might play a role in tumorigenesis of several human cancers, but data on cancer risk in hyperprolactinemia patients are sparse. The aim of this study was to investigate cancer risk in hyperprolactinemia patients.DesignA population-based matched cohort study in Sweden.MethodsThe hyperprolactinemia cohort consisted of patients hospitalized for hyperprolactinemia from 1987 to 1995 identified in the National Patient Register (n=585) and a hospital cohort of prolactinoma patients at Karolinska University Hospital (n=384). For each patient, ten matched individuals were identified via the Register of Population. Cancer occurrence was ascertained via the Swedish Cancer Registry. Hazard ratios (HRs) were estimated by Cox proportional hazards regression.ResultsSeventy-three malignant tumors were identified in the hyperprolactinemia patients and 660 tumors in the comparison group (HR 1.31; 95% confidence interval (CI): 1.02–1.68), mainly attributed to an increased risk of upper gastrointestinal cancer in both males and females (HR 3.69; 95% CI: 1.70–8.03) and hematopoietic cancer in females (HR 3.51; 95% CI: 1.06–11.6). Twelve breast cancers occurred in the female patients, corresponding to an HR of 1.09 (95% CI: 0.60–1.99). Prostate cancer risk in hyperprolactinemia men was reduced (HR 0.40; 95% CI: 0.16–0.99).ConclusionsAn increased overall cancer risk was found in hyperprolactinemia patients, but no increased risk of breast cancer in women and a reduced risk of prostate cancer in men. These findings warrant further investigations and to be confirmed in larger studies but may indicate the importance of an active treatment strategy and follow-up of hyperprolactinemia patients.


2020 ◽  
Vol 74 (4) ◽  
pp. 384-390 ◽  
Author(s):  
Lili Yang ◽  
Min Zhao ◽  
Costan G Magnussen ◽  
Sreenivas P Veeranki ◽  
Bo Xi

BackgroundPrevious studies have shown inconsistent findings on the association between psychological distress and risk of mortality. This study aimed to address this inconsistent association using a large US population-based cohort.MethodsThis study used data from 1997 to 2009 US National Health Interview Survey, which were linked with National Death Index through 31 December 2011. Psychological distress was measured using Kessler-6 scale and was categorised into six groups based on scores as 0, 1–3, 4–6, 7–9, 10–12 and ≥13. Main outcomes were all-cause, cancer-specific and cardiovascular disease (CVD)-specific mortality. Analyses were completed in 2019. Cox proportional hazards models were used to determine the association between psychological distress and mortality.ResultsA total of 330 367 participants aged ≥18 years were included. During a mean follow-up of 8.2 years, 34 074 deaths occurred, including 8320 cancer-related and 8762 CVD-related deaths. There was a dose–response association between psychological distress and all-cause mortality. Compared with the 0 score category, adjusted HRs (95% CIs) for other categorical psychological distress scores, that is, 1–3, 4–6, 7–9, 10–12 and ≥13, were 1.09 (1.05 to 1.12), 1.22 (1.17 to 1.27), 1.38 (1.31 to 1.46), 1.49 (1.40 to 1.59) and 1.57 (1.47 to 1.68), respectively. Corresponding values for cancer-specific mortality were 1.06 (0.99 to 1.12), 1.13 (1.04 to 1.23), 1.27 (1.14 to 1.42), 1.38 (1.22 to 1.57) and 1.32 (1.15 to 1.51), respectively; those for CVD-specific mortality were 1.11 (1.05 to 1.18), 1.22 (1.12 to 1.32), 1.30 (1.17 to 1.45), 1.38 (1.20 to 1.58), and 1.46 (1.27 to 1.68), respectively.ConclusionsWe found a dose–response relationship between psychological distress and all-cause and cause-specific mortality, emphasising the need for early prevention strategies among individuals with potential psychological distress.


Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 1034
Author(s):  
Vincenza Gianfredi ◽  
Annemarie Koster ◽  
Anna Odone ◽  
Andrea Amerio ◽  
Carlo Signorelli ◽  
...  

Our aim was to assess the association between a priori defined dietary patterns and incident depressive symptoms. We used data from The Maastricht Study, a population-based cohort study (n = 2646, mean (SD) age 59.9 (8.0) years, 49.5% women; 15,188 person-years of follow-up). Level of adherence to the Dutch Healthy Diet (DHD), Mediterranean Diet, and Dietary Approaches To Stop Hypertension (DASH) were derived from a validated Food Frequency Questionnaire. Depressive symptoms were assessed at baseline and annually over seven-year-follow-up (using the 9-item Patient Health Questionnaire). We used Cox proportional hazards regression analyses to assess the association between dietary patterns and depressive symptoms. One standard deviation (SD) higher adherence in the DHD and DASH was associated with a lower hazard ratio (HR) of depressive symptoms with HRs (95%CI) of 0.78 (0.69–0.89) and 0.87 (0.77–0.98), respectively, after adjustment for sociodemographic and cardiovascular risk factors. After further adjustment for lifestyle factors, the HR per one SD higher DHD was 0.83 (0.73–0.96), whereas adherence to Mediterranean and DASH diets was not associated with incident depressive symptoms. Higher adherence to the DHD lowered risk of incident depressive symptoms. Adherence to healthy diet could be an effective non-pharmacological preventive measure to reduce the incidence of depression.


Sign in / Sign up

Export Citation Format

Share Document