Publications by authors named "Sarah E Daugherty"

20 Publications

  • Page 1 of 1

Self-reported Prostate Cancer Progression Status Is Accurate: A Validation Study.

Epidemiology 2020 05;31(3):441-447

National Cancer Institute, National Institutes of Health, Rockville, MD.

Background: Studies of prostate cancer progression are important for discovering risk factors that may increase the risk of prostate cancer-specific death; however, little is known about the validity of self-reported prostate cancer progression.

Methods: We conducted a validation study of self-reported prostate cancer progression in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and in a prostate cancer cohort enrolled in a Fred Hutchinson Cancer Research Center (FHCRC)-based study. We calculated measures of validity for self-reported progression, including sensitivity, specificity, positive predictive value, and negative predictive value using medical records as the gold standard.

Results: Our results suggest that ascertaining prostate cancer progression-related events (i.e., prostate-specific antigen elevation, recurrence, metastasis, and use of secondary treatment) through self-report may be a viable option for identifying men whose disease has progressed after diagnosis or initial therapy, particularly when multiple questions related to progression are included in the assessment (aggregate cluster of questions: sensitivity = 0.76 [PLCO]; 0.93 [FHCRC], specificity = 0.80 [PLCO]; 0.97 [FHCRC]). With an aggregate positive predictive value of 0.50 (PLCO), however, our PLCO results suggest that additional medical record verification of self-reported progression events may be necessary to rule out false positives. Most individuals reporting no evidence of progression-related events, however, were true negatives (aggregate negative predictive value = 0.92 [PLCO]; 0.98 [FHCRC]). Thus, there may be limited utility to investing resources in chart review to confirm self-reported nonevents.

Conclusion: Ascertaining prostate cancer progression through self-report provides an efficient and valid approach to enhancing existing cancer cohorts with updated data on progression status. See video abstract at, http://links.lww.com/EDE/B658.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/EDE.0000000000001170DOI Listing
May 2020

Rationale and Design of the Aspirin Dosing-A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness (ADAPTABLE) Trial.

JAMA Cardiol 2020 05;5(5):598-607

Minneapolis Heart Institute, Minneapolis Heart Institute Foundation, Minneapolis.

Importance: Determining the right dosage of aspirin for the secondary prevention treatment of atherosclerotic cardiovascular disease (ASCVD) remains an unanswered and critical question.

Objective: To report the rationale and design for a randomized clinical trial to determine the optimal dosage of aspirin to be used for secondary prevention of ASCVD, using an innovative research method.

Design, Setting, And Participants: This pragmatic, open-label, patient-centered, randomized clinical trial is being conducted in 15 000 patients within the National Patient-Centered Clinical Research Network (PCORnet), a distributed research network of partners including clinical research networks, health plan research networks, and patient-powered research networks across the United States. Patients with established ASCVD treated in routine clinical practice within the network are eligible. Patient recruitment began in April 2016. Enrollment was completed in June 2019. Final follow-up is expected to be completed by June 2020.

Interventions: Participants are randomized on a web platform in a 1:1 fashion to either 81 mg or 325 mg of aspirin daily.

Main Outcomes And Measures: The primary efficacy end point is the composite of all-cause mortality, hospitalization for nonfatal myocardial infarction, or hospitalization for a nonfatal stroke. The primary safety end point is hospitalization for major bleeding associated with a blood-product transfusion. End points are captured through regular queries of the health systems' common data model within the structure of PCORnet's distributed data environment.

Conclusions And Relevance: As a pragmatic study and the first interventional trial conducted within the PCORnet electronic data infrastructure, this trial is testing several unique and innovative operational approaches that have the potential to disrupt and transform the conduct of future patient-centered randomized clinical trials by evaluating treatments integrated in clinical practice while at the same time determining the optimal dosage of aspirin for secondary prevention of ASCVD.

Trial Registration: ClinicalTrials.gov Identifier: NCT02697916.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamacardio.2020.0116DOI Listing
May 2020

Metastatic prostate cancer at diagnosis and through progression in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

Cancer 2019 09 8;125(17):2965-2974. Epub 2019 May 8.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Background: The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial assessed the effect of screening with prostate-specific antigen and a digital rectal examination on prostate cancer mortality. Another endpoint of interest was the burden of total metastatic disease.

Methods: All men in PLCO were assessed for metastatic prostate cancer at diagnosis; men with clinical stage I/II disease were assessed for metastatic progression. The rate of total metastatic disease was defined as metastases found either at diagnosis or through progression divided by person-years (PYs) of follow-up for all men in the trial. Metastatic progression rates were computed among men with clinical stage I/II prostate cancer. Survival among men with metastases at diagnosis was compared with survival among men with metastatic progression.

Results: Among 38,340 men in the intervention arm and 38,343 men in the control arm in PLCO, there were 4974 and 4699 prostate cancer cases, respectively. The rates of total metastatic disease were 4.72 and 4.83 per 10,000 PYs in the intervention and control arms, respectively (rate ratio, 0.98; 95% CI, 0.81-1.18). The rates of metastatic progression among men with clinical stage I/II prostate cancer were 43.7 and 50.5 per 10,000 PYs in the intervention and control arms, respectively (P = .30). Prostate cancer-specific 5- and 10-year survival rates were significantly worse for men with metastatic progression (24% and 19%, respectively) than men with metastases at diagnosis (40% and 26%, respectively).

Conclusions: Rates of total metastatic disease and metastatic progression were similar across arms in PLCO. Survival was worse for men with metastatic progression in comparison with those with metastatic disease at diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.32176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690759PMC
September 2019

Aspirin Use and Mortality in Two Contemporary US Cohorts.

Epidemiology 2018 01;29(1):126-133

Background: Daily aspirin use has been recommended for secondary prevention of cardiovascular disease, but its use for primary prevention remains controversial.

Methods: We followed 440,277 men and women from the NIH-AARP Diet and Health Study (ages 50-71) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (ages 55-74) for mortality for 13 years on average. Frequency of aspirin use was ascertained through self-report, and cause of death by death certificates. We calculated multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality using Cox proportional hazards models for each cohort and combined by meta-analysis.

Results: We found a consistent U-shaped relationship between aspirin use and mortality in both studies, with differential risk patterns for cardiovascular mortality by disease history. Among individuals with a history of cardiovascular disease, daily aspirin use was associated with reduced cardiovascular mortality [HR = 0.78 (95% CI, 0.74, 0.82)]. However, among those without a previous history, we observed no protection for daily aspirin users [HR = 1.06 (1.02, 1.11)], and elevated risk of cardiovascular mortality for those taking aspirin twice daily or more [HR = 1.29 (1.19, 1.39)]. Elevated risk persisted even among participants who lived beyond 5 years of follow-up and used aspirin without other nonsteroidal antiinflammatory drugs [HR = 1.31 (1.17, 1.47)].

Conclusions: Results from these 2 large population-based US cohorts confirm the utility of daily aspirin use for secondary prevention of cardiovascular mortality; however, our data suggest that caution should be exercised in more frequent use, particularly among individuals without a history of cardiovascular disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/EDE.0000000000000746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5718934PMC
January 2018

Do Aspirin and Other NSAIDs Confer a Survival Benefit in Men Diagnosed with Prostate Cancer? A Pooled Analysis of NIH-AARP and PLCO Cohorts.

Cancer Prev Res (Phila) 2017 Jul 15;10(7):410-420. Epub 2017 May 15.

Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland.

Prostate cancer is one of the leading causes of cancer-related death in U.S. men. There is an unmet need to identify modifiable risk factors for prostate cancer survival. Experimental studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) may improve prostate cancer survival through antithrombotic and anti-inflammation mechanisms. Results from previous observational studies have been equivocal, and few have assessed whether an etiologically relevant time window of exposure exists. We sampled incident prostate cancer cases from two large U.S. prospective cohorts, NIH-AARP Diet and Health Study and PLCO Cancer Screening Trial, to investigate whether pre- and postdiagnostic aspirin and non-aspirin NSAID use were associated with prostate cancer-specific and all-cause mortality. Cox proportional hazards regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs). Study-specific results were meta-analyzed using fixed-effects models. Pre- and postdiagnostic aspirin or non-aspirin NSAID use were not statistically significantly associated with prostate cancer-specific mortality. However, occasional (less than daily) and daily aspirin users five years or more before prostate cancer diagnosis had 18% (HR = 0.82; 95% CI = 0.75-0.90) and 15% (HR = 0.85; 95% CI = 0.77-0.94) reduced all-cause mortality versus nonusers. Similarly, postdiagnostic occasional and daily aspirin use were associated with 17% (HR = 0.83; 95% CI=0.72-0.95) and 25% (HR = 0.75; 95% CI = 0.66-0.86) reduced all-cause mortality, independent of prediagnostic aspirin use. This study suggests that aspirin or non-aspirin NSAIDs are not associated with prostate cancer survival. However, aspirin use both before and after prostate cancer diagnosis was associated with longer overall survival, highlighting the importance of comorbidity prevention among prostate cancer survivors. .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1940-6207.CAPR-17-0033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5516895PMC
July 2017

A prospective study of alcohol consumption and renal cell carcinoma risk.

Int J Cancer 2015 Jul 10;137(1):238-42. Epub 2014 Dec 10.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Department of Health and Human Services, Bethesda, MD.

Recent epidemiological studies suggest that alcohol consumption may reduce renal cell carcinoma (RCC) risk, although inconsistent findings have been reported by sex and alcoholic beverage type. To better understand the relationship between alcohol consumption and RCC risk, we conducted an analysis within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We followed up participants in the analytic cohort (N = 107,998) through 2010 for incident RCC (N = 408), and computed hazard ratios (HRs) and 95% confidence intervals (CIs) for alcohol intake using Cox regression with adjustment for age, sex, race, study center, hypertension, body mass index, and smoking status. In this study population increasing alcohol consumption was associated with reduced RCC risk compared to non-drinkers (>9.75 g day(-1) : HR, 0.67; 95%CI, 0.50 to 0.89; p trend = 0.002). We observed similar patterns of association for men and women as well as by alcohol beverage type. In analyses stratified by smoking status, the inverse association with consumption was apparent for ever smokers (HR, 0.51; 95%CI, 0.36 to 0.73; p trend<0.0001) but not among never smokers (HR, 1.08; 95%CI, 0.66 to 1.76; P trend = 0.78; p interaction = 0.01). Our study findings offer further support that alcohol consumption is associated with reduced RCC risk, regardless of sex or alcoholic beverage type. The finding of interaction with smoking is novel and requires confirmation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.29359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405442PMC
July 2015

Patient-powered research networks: building capacity for conducting patient-centered clinical outcomes research.

J Am Med Inform Assoc 2014 Jul-Aug;21(4):583-6. Epub 2014 May 12.

Patient-Centered Outcomes Research Institute, Washington, DC, USA.

The Patient-Centered Outcomes Research Institute (PCORI) recently launched PCORnet to establish a single inter-operable multicenter data research network that will support observational research and randomized clinical trials. This paper provides an overview of the patient-powered research networks (PPRNs), networks of patient organizations focused on a particular health condition that are interested in sharing health information and engaging in research. PPRNs will build on their foundation of trust within the patient communities and draw on their expertise, working with participants to identify true patient-centered outcomes and direct a patient-centered research agenda. The PPRNs will overcome common challenges including enrolling a diverse and representative patient population; engaging patients in governance; designing the data infrastructure; sharing data securely while protecting privacy; prioritizing research questions; scaling small networks into a larger network; and identifying pathways to sustainability. PCORnet will be the first distributed research network to bring PCOR to national scale.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/amiajnl-2014-002758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4078295PMC
August 2014

The risk of amyotrophic lateral sclerosis after cancer in U.S. elderly adults: a population-based prospective study.

Int J Cancer 2014 Oct 28;135(7):1745-50. Epub 2014 Feb 28.

U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, 9609 Medical Center Drive, Rockville, MD.

Although epidemiologic studies have examined the risk of amyotrophic lateral sclerosis (ALS) in relation to cancer, none have been large population-based studies using incident ALS and adjusting for medical surveillance. Addressing those limitations, all first primary cancer cases from the Surveillance, Epidemiology and End Results (SEER) Program (1992-2005), linked to Medicare claims data were used. Cases were followed from cancer diagnosis until the earliest date of ALS diagnosis, a break in Medicare claims data, death, age 85 or December 31, 2005. A comparison group from a 5% random Medicare sample in the SEER areas who were cancer-free and censored as above, or until a cancer diagnosis were selected. ALS outcomes were derived from medical claims. The proportional hazards models to estimate ALS hazard ratios (HRs), using age as the time scale, adjusting for sex, race and physician visits, and stratifying the baseline hazard on birth year and SEER registry were used. A total of 303 ALS cases were ascertained in cancer patients (2,154,062 person-years) compared with 246 ALS cases (2,467,634 person-years) in the reference population. There was no overall relationship between cancer and ALS (HR = 0.99; 95% CI = 0.81-1.22), nor by gender or race. Except for an elevated ALS risk in the first year after a leukemia diagnosis, the relationship between site-specific cancers and ALS was null after correcting for multiple comparisons. Having a cancer diagnosis was not associated with an overall risk of incident ALS. The short-term ALS risk after leukemia may reflect screening or reporting errors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.28795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4107108PMC
October 2014

Analgesic use and patterns of estrogen metabolism in premenopausal women.

Horm Cancer 2014 Apr 10;5(2):104-12. Epub 2014 Jan 10.

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Ave., Boston, MA, 02115, USA.

Analgesic use has been hypothesized to reduce the risk of some cancers, with inverse associations between analgesics and colon cancer, and suggestive inverse associations for breast cancer. Estrogen metabolites (EM) have genotoxic and estrogenic potential; genotoxicity may differ by hydroxylation pathway. Analgesic use may impact patterns of estrogen metabolism; effects of analgesics on disease risk could be mediated through these patterns. We conducted a cross-sectional study among 603 premenopausal women in the Nurses' Health Study II. Frequency of aspirin, non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen use was reported via questionnaire; average frequency in 1997 and 1999 was calculated. Women provided urine samples between 1996 and 1999, collected during the mid-luteal phase of the menstrual cycle. Urinary EM were quantified using high-performance liquid chromatography-tandem mass spectrometry. We observed no association between analgesic use and estradiol, estrone, or specific pathways of estrogen metabolism. Women reporting more frequent aspirin use had lower methylated 2-catechols (e.g., 2-hydroxyestrone-3-methyl ether, 2+ days/week vs. non-use: 0.95 vs. 1.21 pmol/mg creatinine; p difference = 0.01, p trend = 0.07). Non-aspirin NSAID use was positively associated with 17-epiestriol (4+ days/week vs. non-use: 2.48 vs. 1.52 pmol/mg creatinine; p difference = 0.01, p trend = 0.11). Acetaminophen use was positively associated with total EM (2+ days/week vs. non-use: 236 vs. 198 pmol/mg creatinine; p difference = 0.02, p trend = 0.11), 2-hydroxyestrone-3-methyl ether (1.6 vs. 1.1 pmol/mg creatinine; p difference < 0.01, p trend = 0.02), and 16α-hydroxyestrone (17 vs. 12 pmol/mg creatinine; p difference = 0.01, p trend = 0.05). This study provides the first assessment of analgesic use and patterns of estrogen metabolism in women. While we observed some associations between analgesics and individual EM, no clear patterns emerged.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12672-013-0167-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3976755PMC
April 2014

Hysterectomy and kidney cancer risk: a meta-analysis.

Int J Cancer 2014 Jan 30;134(2):405-10. Epub 2013 Jul 30.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Department of Health and Human Services, Bethesda, Maryland.

Recent cohort findings suggest that women who underwent a hysterectomy have an elevated relative risk of kidney cancer, although evidence from past studies has been inconsistent. We conducted a systematic review and meta-analysis of published cohort and case-control studies to summarize the epidemiologic evidence investigating hysterectomy and kidney cancer. Studies published from 1950 through 2012 were identified through a search of PubMed and of references from relevant publications. Meta-analyses were conducted using random-effects models to estimate summary relative risks (SRRs) and 95% confidence intervals (CIs) for hysterectomy, age at hysterectomy (<45, 45+ years) and time since hysterectomy (<10, 10+ years). The SRR for hysterectomy and kidney cancer for all published studies (seven cohort, six case-control) was 1.29 (95% CI, 1.16-1.43), with no evidence of between-study heterogeneity or publication bias. The summary effect was slightly weaker, although still significant, for cohorts (SRR, 1.26; 95% CI, 1.11-1.42) compared with case-control findings (1.37; 95% CI, 1.09-1.73) and was observed irrespective of age at hysterectomy, time since the procedure and model adjustment for body mass index, smoking status and hypertension. Women undergoing a hysterectomy have an approximate 30% increased relative risk of subsequent kidney cancer. Additional research is needed to elucidate the biological mechanisms underlying this association.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.28352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834077PMC
January 2014

Reproductive factors and kidney cancer risk in 2 US cohort studies, 1993-2010.

Am J Epidemiol 2013 Jun 26;177(12):1368-77. Epub 2013 Apr 26.

Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

Clinical and experimental findings suggest that female hormonal and reproductive factors could influence kidney cancer development. To evaluate this association, we conducted analyses in 2 large prospective cohorts (the National Institutes of Health-AARP Diet and Health Study (NIH-AARP), 1995-2006, and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), 1993-2010). Cohort-specific and aggregated hazard ratios and 95% confidence intervals relating reproductive factors and kidney cancer risk were computed by Cox regression. The analysis included 792 incident kidney cancer cases among 283,952 postmenopausal women. Women who had undergone a hysterectomy were at a significantly elevated kidney cancer risk in both NIH-AARP (hazard ratio = 1.28, 95% confidence interval: 1.09, 1.50) and PLCO (hazard ratio = 1.41, 95% confidence interval: 1.06, 1.88). Similar results were observed for both cohorts after analyses were restricted to women who had undergone a hysterectomy with or without an oophorectomy. For the NIH-AARP cohort, an inverse association was observed with increasing age at menarche (P for trend = 0.02) and increasing years of oral contraceptive use (P for trend = 0.02). No clear evidence of an association with parity or other reproductive factors was found. Our results suggest that hysterectomy is associated with increased risk of kidney cancer. The observed associations with age at menarche and oral contraceptive use warrant further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/aje/kws406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3676151PMC
June 2013

Reproductive factors and menopausal hormone therapy and bladder cancer risk in the NIH-AARP Diet and Health Study.

Int J Cancer 2013 Jul 12;133(2):462-72. Epub 2013 Feb 12.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.

The incidence of bladder cancer among women is at least one-third to one-fourth that observed among men in many countries. Even after accounting for known risk factors, the reason for this gender disparity remains unexplained. We conducted a comprehensive evaluation of reproductive factors and exogenous hormone use with a primary focus on menopausal hormone therapy use and risk of bladder cancer in women in the NIH-AARP Diet and Health Study. Reproductive and hormonal factors were ascertained on the baseline questionnaire in 1995-1996 among 201,492 females who were followed until December 31, 2006. During follow-up, 651 cases of bladder cancer were diagnosed. A subset of women provided detailed information on use of MHT in a second questionnaire in 1996-1997. In this analysis, 127,361 females were followed through June 30, 2002 and 198 incident bladder cancer cases were identified. Cox proportional hazard models, adjusted for smoking status, cigarettes per day and body mass index using age as the time metric, were used to obtain hazard ratios (HRs). A reduced risk was observed among parous women (HR=0.76; 95% CI 0.62-0.93) and women who reported late age at menarche (≥15 years) (HR=0.57; 95% CI 0.39-0.84). Women who reported ever using estrogen and progestin therapy had a decreased risk (HR=0.53; 95% CI: 0.34-0.83) compared with women who did not report MHT use. No association was observed for estrogen only users (HR=0.82; 95% CI: 0.58-1.15). Our results suggest a putative role for sex hormones in the etiology of bladder cancer among women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.28022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646919PMC
July 2013

The association between cancer and amyotrophic lateral sclerosis.

Cancer Causes Control 2013 Jan 23;24(1):55-60. Epub 2012 Oct 23.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health/ DHHS, 6120 Executive Blvd., Bethesda, MD 20892-7238, USA.

Objective: Increasing evidence suggests that some neurodegenerative disorders, such as Parkinson's disease, are inversely related to cancer. Few epidemiologic studies have examined the relationship between cancer and amyotrophic lateral sclerosis (ALS), another major neurodegenerative disease. This study addresses that gap.

Methods: Using data from 16 population-based cancer registries of the Surveillance, Epidemiology, and End Results (SEER) Program of the U.S. National Cancer Institute and death certificates, we followed 2.7 million cancer survivors who were diagnosed between 1973 and 2007, and who survived at least 1 year following cancer diagnosis. The standardized mortality ratio (SMR) of observed to expected ALS deaths in cancer survivors was calculated.

Results: A total of 1,216 ALS deaths were reported among 1 year survivors of cancer over 16.6 million person-years of follow-up. ALS mortality was not significantly associated with the incidence of total cancers [SMR = 1.00 (95 % confidence interval (CI), 0.95-1.06)]. There was, however, a significantly elevated risk of ALS death among survivors of melanoma [SMR = 1.49 (95 % (CI), 1.17-1.85)] and of tongue cancer [SMR = 2.57 (95 % CI, 1.41-4.32)], and a significantly reduced ALS death risk among prostate cancer survivors [SMR = 0.86 (95 % CI, 0.76-0.96)].

Conclusions: Cancer at certain sites may be related to risk of ALS death. Possible biologic factors linking ALS to these cancers are discussed. Future studies should attempt to confirm these associations using incident ALS outcomes. Establishing relationships between cancer and neurodegenerative diseases, such as ALS, opens new opportunities for understanding related pathophysiologic and therapeutic possibilities for these diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10552-012-0089-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3529829PMC
January 2013

Nonsteroidal anti-inflammatory drugs and glioma in the NIH-AARP Diet and Health Study cohort.

Cancer Prev Res (Phila) 2011 Dec 1;4(12):2027-34. Epub 2011 Sep 1.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland, USA.

Several case-control studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) reduce risk for glioblastoma, an aggressive form of brain cancer. Prospective investigations have not observed such an association, but these studies lacked adequate brain cancer case numbers and did not stratify by histologic subtype. We prospectively investigated the association between NSAID use and risk of all glioma as well as the risk of glioblastoma subtype in the National Institutes of Health (NIH)-AARP Diet and Health Study. The frequency of aspirin and nonaspirin NSAID use 1 year prior to baseline was ascertained using a self-administered questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using Cox regression models with age as the underlying time metric, adjusted for sex, race, and history of heart disease. The analysis included 302,767 individuals, with 341 incident glioma cases (264 glioblastoma). No association was observed between regular use (>2 times/wk) of aspirin and risk of glioma (HR = 1.16; 95% CI, 0.87-1.56) or glioblastoma (HR = 1.17; 95% CI, 0.83-1.64) as compared with no use. Null associations were also observed for nonaspirin NSAID use (HR for glioma = 0.90; 95% CI, 0.65-1.25 and HR for glioblastoma = 0.83; 95% CI, 0.56-1.20) as compared with no use. Our findings from this large prospective study do not support an inverse association between NSAIDs and risk of all glioma or glioblastoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1940-6207.CAPR-11-0274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388115PMC
December 2011

Nonsteroidal antiinflammatory drugs and bladder cancer: a pooled analysis.

Am J Epidemiol 2011 Apr 2;173(7):721-30. Epub 2011 Mar 2.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health/DHHS, 6120 Executive Boulevard, Rockville, MD 20852, USA.

Case-control studies have shown that regular use of nonsteroidal antiinflammatory drugs (NSAIDs) decreases bladder cancer risk, but few cohort studies have evaluated this association. The authors investigated NSAID use and bladder cancer in 3 large prospective studies (NIH-AARP Diet and Health Study; Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial; and U.S. Radiologic Technologists Study). Frequency of aspirin and nonaspirin NSAID use 1 year prior to baseline was ascertained using self-administered questionnaires. Study-specific hazard ratios and 95% confidence intervals were estimated using Cox regression models and were combined using a fixed-effects meta-analytic model. Data from all studies were aggregated, and aggregated hazard ratios were estimated. The analysis included 508,842 individuals, with 2,489 incident cases of bladder cancer. A reduction in risk was observed for individuals who reported regular use (>2 times/week) of nonaspirin NSAIDs compared with those who reported no use (hazard ratio (HR) = 0.92, 95% confidence interval (CI): 0.81, 1.04). The risk reduction was limited to nonsmokers (HR = 0.58, 95% CI: 0.41, 0.83) (P(trend) = 0.008) (P(interaction) = 0.02). No association was observed between regular aspirin use and bladder cancer risk (HR = 1.04, 95% CI: 0.94, 1.15). Results suggest that nonaspirin NSAIDs, but not aspirin, are associated with a reduction in risk of bladder cancer, particularly for nonsmokers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/aje/kwq437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105281PMC
April 2011

Variants in the alpha-Methylacyl-CoA racemase gene and the association with advanced distal colorectal adenoma.

Cancer Epidemiol Biomarkers Prev 2007 Aug;16(8):1536-42

Divison of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, 6120 Executive Boulevard, EPS Rm 8113, Bethesda, MD 20892, USA.

Background: alpha-Methylacyl-CoA racemase (AMACR), an enzyme involved in oxidation of branched chain fatty acids and cholesterol metabolites, as well as ibuprofen metabolism, is overexpressed in colorectal adenomas and cancer. AMACR gene variants have been associated with hereditary prostate cancer, but no studies have evaluated their etiologic role in colorectal carcinogenesis.

Methods: We conducted a case-control study of 725 advanced distal colorectal adenoma cases and 729 frequency-matched controls from the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Seven AMACR polymorphisms were genotyped. Unconditional logistic regression models were used to evaluate the associations adjusting for age at randomization and gender.

Results: The 201L allele of S201L [TT versus CC: odds ratio (OR), 1.74; 95% confidence interval (95% CI), 1.15-2.62; TC versus CC: OR, 1.17; 95% CI, 0.93-1.49] and the 277E allele of K277E (GG versus AA: OR, 1.66; 95% CI, 1.03-2.68; GA versus AA: OR, 1.21; 95% CI, 0.96-1.53) were associated with increased risk of advanced distal colorectal adenoma (both P(trend)
Conclusion: Our study identified variants in AMACR associated with advanced distal colorectal adenoma and pointed to potential interactions with ibuprofen use.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-07-0117DOI Listing
August 2007

Polymorphic variants in alpha-methylacyl-CoA racemase and prostate cancer.

Prostate 2007 Oct;67(14):1487-97

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.

Background: Alpha-methylacyl-CoA racemase (AMACR), which prepares branched chain fatty acids to be metabolized for energy and is implicated in the activation of the COX-inhibiting form of ibuprofen, is overexpressed in prostate cancer and its precursor lesions. Significant differences in AMACR allele frequencies have been reported for hereditary prostate cancer (HPC), but the relevance of AMACR in the context of its substrates have not been studied.

Methods: We conducted a nested case-control study of 1,318 prostate cancer cases and 1,842 controls from the screening arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Five non-synonymous (nsSNP) and two intronic AMACR polymorphisms were genotyped. Conditional logistic regression models were used to evaluate the associations between the genetic variants and prostate cancer.

Results: Overall, prostate cancer was not related to AMACR gene variants; however, risks for prostate cancer were significantly reduced among regular ibuprofen users who carried allele variants at four nsSNP loci (M9V, D175G, S201L, and K277E; all P(trend) < 0.05) or carried the TGTGCG haplotype (OR = 0.65; 95% CI 0.44-0.97). No AMACR-related associations were noted among nonregular ibuprofen users (all P(interaction) > 0.33).

Conclusion: AMACR gene variants were unrelated to prostate cancer overall in this study. The protective associations observed among ibuprofen users suggest that AMACR gene variants may enhance the chemopreventive effects of ibuprofen on prostate cancer risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pros.20635DOI Listing
October 2007

RNASEL Arg462Gln polymorphism and prostate cancer in PLCO.

Prostate 2007 Jun;67(8):849-54

Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

Background: The Gln allele of the Arg462Gln polymorphism in RNASEL results in a threefold decrease in enzymatic activity, a reported deficiency in apoptotic response, and has been associated with prostate cancer in some high-risk family studies. The relationship of this variant to sporadic prostate cancer remains uncertain.

Methods: We conducted a nested case-control study of 1,317 prostate cancer cases and 1,842 controls from the screening arm of the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial. Conditional logistic regression was used to evaluate the association between the RNASEL Arg462Gln polymorphism and prostate cancer.

Results: No statistically significant association was observed between the Arg462Gln polymorphism and prostate cancer (compared to Arg/Arg, Gln/Arg: OR= 0.99 95% CI 0.84-1.16; Gln/Gln: OR= 0.95 95% CI 0.74-1.21), although slight non-significant differences in risk were observed among men with the Gln/Gln genotype by stage and grade.

Conclusions: These results suggest that the RNASEL Gln/Gln genotype does not play an important role in the etiology of prostate cancer in the general population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pros.20537DOI Listing
June 2007

Genetic polymorphisms of interleukin-1B (IL-1B), IL-6, IL-8, and IL-10 and risk of prostate cancer.

Cancer Res 2006 Apr;66(8):4525-30

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.

Chronic intraprostatic inflammation is suspected to play a role in the pathogenesis of prostate cancer. Polymorphisms in cytokine genes can influence inflammation and immune response and may be related to the risk of prostate cancer. Four common single nucleotide polymorphisms (SNPs) in the genes encoding interleukin-1B (IL-1B), IL-6, and IL-8 were assessed in 503 prostate cancer cases and 652 controls, and three SNPs in IL-10 were assessed in an additional 817 prostate cancer cases and 1,190 controls (for a total of 1,320 prostate cancer cases and 1,255 controls). Cases and controls were selected from the on-going Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial and were frequency matched on age, ethnicity, time-period since initial screening, and date of blood draw. Single-locus analyses were conducted using conditional logistic regression. In addition, we did a haplotype analysis for the three IL-10 SNPs tested. Overall, no associations were detected between the seven polymorphisms in the four cytokine genes examined in this study and prostate cancer risk. Further stratifying by use of nonsteroidal anti-inflammatory drugs did not modify the associations. Findings were similar for early or advanced prostate cancers. Similarly, we observed no association between the major IL-10 haplotypes and the risk of prostate cancer. At least seven common polymorphisms in genes of inflammatory cytokines IL-1B, IL-6, IL-8, and IL-10 do not seem to play a role in the risk of prostate cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/0008-5472.CAN-05-3987DOI Listing
April 2006

No evidence for anticipation in lymphoproliferative tumors in population-based samples.

Cancer Epidemiol Biomarkers Prev 2005 May;14(5):1245-50

Division of Cancer Epidemiology and Genetics, National Cancer Institute, EPS Room 511, 6120 Executive Boulevard, Bethesda, MD 20892, USA.

Genetic anticipation in familial non-Hodgkin's lymphoma, Hodgkin's lymphoma, and chronic lymphocytic leukemia (CLL) has been consistently reported in the literature. However, most of these findings were based on data from families ascertained for genetic studies. Fecundity bias, right censoring bias, and secular trends can lead to erroneous conclusions regarding the presence of anticipation. Our report investigates anticipation in four lymphoproliferative cancers, non-Hodgkin's lymphoma, Hodgkin's lymphoma, CLL, and multiple myeloma, drawn from Swedish and Danish population-based registries. We used marginal survival methods to test for a relative difference in age at diagnosis between parents and offspring and to account for other risk factors, staggered entries, censored data, and correlations among relatives. Changes in incidence rates of lymphoproliferative tumors were accommodated in the models by using time-varying covariates for different periods of diagnosis. Whereas no anticipation was observed for Hodgkin's lymphoma, CLL, and multiple myeloma, our initial model, which controlled for gender and country, suggested a significant difference (hazard ratio, 0.5; 95% confidence interval, 0.33-0.75) in age at diagnosis between the parents and offspring in the non-Hodgkin's lymphoma sample. However, once we accounted for the significant change in non-Hodgkin's lymphoma incidence over time, the statistical difference between parents and offspring disappeared (hazard ratio, 0.99; 95% confidence interval, 0.56-1.76). Our results emphasize the importance of considering secular trends when evaluating the possibility of anticipation in lymphoproliferative cancers. This is the first study to consider the changes of incidence over time as a source of bias when evaluating anticipation in lymphoproliferative cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-04-0783DOI Listing
May 2005