Associations between metabolites and pancreatic cancer risk in a large prospective epidemiological study

ObjectiveTo assess whether prediagnostic metabolites were associated with incident pancreatic ductal adenocarcinoma (PDAC) in a prospective cohort study.DesignWe conducted an untargeted analysis of 554 known metabolites measured in prediagnostic serum (up to 24 years) to determine their association with incident PDAC in a nested case-control study of male smokers (372 matched case-control sets) and an independent nested case-control study that included women and non-smokers (107 matched sets). Metabolites were measured using Orbitrap Elite or Q-Exactive high-resolution/accurate mass spectrometers. Controls were matched to cases by age, sex, race, date of blood draw, and follow-up time. We used conditional logistic regression adjusted for age to calculate ORs and 95% CIs for a 1 SD increase in log-metabolite level separately in each cohort and combined the two ORs using a fixed-effects meta-analysis.ResultsThirty-one metabolites were significantly associated with PDAC at a false discovery rate <0.05 with 12 metabolites below the Bonferroni-corrected threshold (p<9.04×10–5). Similar associations were observed in both cohorts. The dipeptides glycylvaline, aspartylphenylalanine, pyroglutamylglycine, phenylalanylphenylalanine, phenylalanylleucine and tryptophylglutamate and amino acids aspartate and glutamate were positively while the dipeptides tyrosylglutamine and α-glutamyltyrosine, fibrinogen cleavage peptide DSGEGDFXAEGGGVR and glutathione-related amino acid cysteine-glutathione disulfide were inversely associated with PDAC after Bonferroni correction. Five top metabolites demonstrated significant time-varying associations (p<0.023) with the strongest associations observed 10–15 years after participants’ blood collection and attenuated thereafter.ConclusionOur results suggest that prediagnostic metabolites related to subclinical disease, γ-glutamyl cycle metabolism and adiposity/insulin resistance are associated with PDAC.

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Identification of symptoms associated with the diagnosis of pancreatic exocrine and neuroendocrine neoplasms: a nested case-control study of the UK population

British Journal of General Practice ◽

10.3399/bjgp.2021.0153 ◽

2021 ◽

pp. BJGP.2021.0153

Author(s):

Weiqi Liao ◽

Ashley Kieran Clift ◽

Martina Patone ◽

Carol Coupland ◽

Arturo González-Izquierdo ◽

...

Keyword(s):

Case Control Study ◽

Conditional Logistic Regression ◽

Stage Iv ◽

Case Control ◽

Ductal Adenocarcinoma ◽

Incidence Density ◽

Neuroendocrine Neoplasms ◽

Dark Urine ◽

Nested Case Control ◽

Control Study

Background: Pancreatic cancer has the worst survival rate among all cancers. Almost 70% of patients were diagnosed at Stage IV. Aim: This study aimed to investigate the symptoms associated with the diagnoses of pancreatic ductal adenocarcinoma (PDAC) and neuroendocrine neoplasms (PNEN), comparatively characterise the symptomatology between the two tumour types to inform earlier diagnosis. Design and Setting: A nested case-control study was conducted using data from the QResearch database. Patients aged ≥25 years and diagnosed with PDAC or PNEN during 2000-2019 were the cases. Up to 10 controls from the same general practice were matched with each case by age, sex, and calendar year using incidence density sampling. Methods: Conditional logistic regression was used to investigate the association between the forty-two shortlisted symptoms and the diagnoses of PDAC/PNEN in different timeframes relative to the index date, adjusting for patients’ sociodemographic characteristics, lifestyle, and relevant comorbidities. Results: There were 23,640 patients diagnosed with PDAC and 596 with PNEN. Twenty-three symptoms were significantly associated with PDAC, and nine symptoms with PNEN. Jaundice and gastrointestinal bleeding were the two alarm symptoms for both tumours. Thirst and dark urine were the two new identified symptoms for PDAC. The risk of unintentional weight loss may be longer than two years before the diagnosis of PNEN. Conclusion: PDAC and PNEN have overlapping symptom profiles. The QCancer (Pancreas) risk prediction model could be updated by including the newly identified symptoms and comorbidities, which could help GP identify high-risk patients for timely investigation in primary care.

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Association of Mesothelioma Deaths With Cumulated Neighborhood Exposures Due to a Large-Scale Asbestos Cement Plant in Amagasaki City, Japan: A Nested Case-control Study

10.21203/rs.3.rs-574038/v1 ◽

2021 ◽

Author(s):

Yuri Kitamura ◽

Ling Zha ◽

Rong Liu ◽

Masayuki Shima ◽

Tomoki Nakaya ◽

...

Keyword(s):

Occupational Exposure ◽

Large Scale ◽

Case Control Study ◽

Conditional Logistic Regression ◽

Asbestos Exposure ◽

Case Control ◽

Asbestos Cement ◽

Nested Case Control ◽

Dose Dependent ◽

Control Study

Abstract BackgroundAlthough a causal relationship between mesothelioma and asbestos exposure is well known, few studies have shown a relationship to non-occupational exposure, including neighborhood exposure, most likely because of the large effect size of occupational exposure. The aim of this study was to quantify the risk of malignant mesothelioma death associated with neighborhood asbestos exposure due to a large-scale asbestos-cement (AC) plant in Amagasaki, Japan, by properly adjusting for occupational exposure. MethodsThis was a nested case-control study in which a fixed population of 143,929 residents who had been living in Amagasaki City between 1975 and 2002 were followed from 2002 to 2015. All 133 cases and 403 matched controls were interviewed about their occupational, domestic, household, and neighborhood asbestos exposures. Odds ratios (ORs) for mesothelioma death associated with neighborhood exposure were estimated by a conditional logistic-regression model that adjusted for other asbestos exposures. We adopted cumulative indices that considered residence-specific asbestos (crocidolite) concentrations and durations during the potential exposure period of 1957-1975 to evaluate individual neighborhood exposures.ResultsThere was an increasing, dose-dependent risk of mesothelioma death associated with neighborhood exposure, demonstrated by ORs in the highest quintile category that were 21.4 (95%CI: 5.8 to 79.2) for all, 23.7 (95% CI: 3.8-147.2) for males and 26.0 (95% CI: 2.8-237.5) for females, compared to the lowest quintile, respectively. These results clearly demonstrated no substantial differences between males and females in relation to the magnitude of risk from neighborhood exposure.Our findings suggest that the risk of mesothelioma death associated with neighborhood exposure persists and will not be diminished for many years, even though it has been decades since the AC plant closed. ConclusionsBy adjusting for occupational and other asbestos exposures, a dose-dependent relationship was demonstrated between mesothelioma death and neighborhood asbestos exposure from a large-scale AC plant.

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Red blood cell membrane trans fatty acid levels and risk of non-Hodgkin lymphoma: a prospective nested case–control study

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqaa251 ◽

2020 ◽

Vol 112 (6) ◽

pp. 1576-1583

Author(s):

Andres V Ardisson Korat ◽

Yu-Han Chiu ◽

Kimberly A Bertrand ◽

Shumin Zhang ◽

Mara M Epstein ◽

...

Keyword(s):

Logistic Regression ◽

Fatty Acid ◽

Case Control Study ◽

Positive Association ◽

Case Control ◽

Blood Draw ◽

Non Hodgkin Lymphoma ◽

Rbc Membrane ◽

Nested Case Control ◽

Control Study

ABSTRACT Background Trans fatty acid (TFA) intake persists in much of the world, posing ongoing threats to public health that warrant further elucidation. Published evidence suggests a positive association of self-reported TFA intake with non-Hodgkin lymphoma (NHL) risk. Objectives To confirm those reports, we conducted a prospective study of prediagnosis RBC membrane TFA levels and risk of NHL and common NHL histologic subtypes. Methods We conducted a nested case–control study in Nurses’ Health Study and Health Professionals Follow-Up Study participants with archived RBC specimens and no history of cancer at blood draw (1989–1090 and 1994–1995, respectively). We confirmed 583 incident NHL cases (332 women and 251 men) and individually matched 583 controls on cohort (sex), age, race, and blood draw date/time. We analyzed RBC membrane TFA using GLC (in 2013–2014) and expressed individual TFA levels as a percentage of total fatty acids. We used unconditional logistic regression adjusted for the matching factors to estimate ORs and 95% CIs for overall NHL risk per 1 SD increase in TFA level and assessed histologic subtype-specific associations with multivariable polytomous logistic regression. Results Total and individual TFA levels were not associated with risk of all NHL or most subtypes. We observed a positive association of total TFA levels with diffuse large B cell lymphoma (DLBCL) risk [n = 98 cases; OR (95% CI) per 1 SD increase: 1.30 (1.05, 1.61); P = 0.015], driven by trans 18:1n–9(ω-9)/elaidic acid [OR (95% CI): 1.34 (1.08, 1.66); P = 0.007], trans 18:1n–7/vaccenic acid [OR (95% CI): 1.28 (1.04, 1.58); P = 0.023], and trans 18:2n–6t,t [OR (95% CI): 1.26 (1.01, 1.57); P = 0.037]. Conclusions Our findings extended evidence for TFA intake and DLBCL risk but not for other NHL subtypes. Reduced TFA consumption through dietary choices or health policy measures may support prevention of DLBCL, an aggressive NHL subtype.

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Depression in individuals who subsequently develop inflammatory bowel disease: a population-based nested case–control study

Gut ◽

10.1136/gutjnl-2020-322308 ◽

2020 ◽

pp. gutjnl-2020-322308 ◽

Cited By ~ 1

Author(s):

Jonathan Blackwell ◽

Sonia Saxena ◽

Irene Petersen ◽

Matthew Hotopf ◽

Hanna Creese ◽

...

Keyword(s):

Case Control Study ◽

Conditional Logistic Regression ◽

Subsequent Development ◽

Case Control ◽

Practice Research ◽

Clinical Practice Research Datalink ◽

Gi Symptoms ◽

Nested Case Control ◽

Incident Cases ◽

Control Study

ObjectiveDepression is a potential risk factor for developing IBD. This association may be related to GI symptoms occurring before diagnosis. We aimed to determine whether depression, adjusted for pre-existing GI symptoms, is associated with subsequent IBD.DesignWe conducted a nested case–control study using the Clinical Practice Research Datalink identifying incident cases of UC and Crohn’s disease (CD) from 1998 to 2016. Controls without IBD were matched for age and sex. We measured exposure to prevalent depression 4.5–5.5 years before IBD diagnosis. We created two sub-groups with prevalent depression based on whether individuals had reported GI symptoms before the onset of depression. We used conditional logistic regression to derive ORs for the risk of IBD depending on depression status.ResultsWe identified 10 829 UC cases, 4531 CD cases and 15 360 controls. There was an excess of prevalent depression 5 years before IBD diagnosis relative to controls (UC: 3.7% vs 2.7%, CD 3.7% vs 2.9%). Individuals with GI symptoms prior to the diagnosis of depression had increased adjusted risks of developing UC and CD compared with those without depression (UC: OR 1.47, 95% CI 1.21 to 1.79; CD: OR 1.41, 95% CI 1.04 to 1.92). Individuals with depression alone had similar risks of UC and CD to those without depression (UC: OR 1.13, 95% CI 0.99 to 1.29; CD: OR 1.12, 95% CI 0.91 to 1.38).ConclusionsDepression, in the absence of prior GI symptoms, is not associated with subsequent development of IBD. However, depression with GI symptoms should prompt investigation for IBD.

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Trimethylamine N-Oxide Metabolites in Early Pregnancy and Risk of Gestational Diabetes: A Nested Case-Control Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2019-00710 ◽

2019 ◽

Vol 104 (11) ◽

pp. 5529-5539 ◽

Cited By ~ 3

Author(s):

Xiaoxu Huo ◽

Jing Li ◽

Yun-Feng Cao ◽

Sai-Nan Li ◽

Ping Shao ◽

...

Keyword(s):

Gestational Diabetes ◽

Early Pregnancy ◽

Case Control Study ◽

Conditional Logistic Regression ◽

Full Range ◽

Case Control ◽

Conversion Ratio ◽

Additive Interaction ◽

Nested Case Control ◽

Control Study

Abstract Objectives This study aimed to investigate the associations between trimethylamine N-oxide (TMAO) and related metabolites in early pregnancy and the risk of gestational diabetes mellitus (GDM). Design A prospective cohort of 22,302 pregnant women from 2010 to 2012 in Tianjin, China, was used to perform a nested case-control study. A total of 243 women with GDM and 243 women without GDM matched by maternal age (±1 year) were used as cases and controls, respectively. Conditional logistic regression and restricted cubic spline were used to examine the full-range risk associations between individual TMAOs metabolites at the first antenatal care visit with GDM. Trimethylamine conversion ratio (TMAR) was defined as trimethylamine (TMA)/its precursors, and trimethylamine N-oxide conversion ratio (TMAOR) was defined as TMAO/TMA. An additive interaction between high TMAR and low TMAOR indicates a state of TMA accumulation, and a mathematical interaction between high TMAR and high TMAOR indicates accumulation of TMAO. Results TMA was linearly associated with GDM, whereas TMA precursors and TMAO were inversely associated with GDM with clear threshold effects, i.e., 16 nmol/mL for TMAO, 200 nmol/mL for betaine, 112 nmol/mL for l-carnitine, and 110 and 270 nmol/mL for cholinechloride (a U-shaped relationship). Copresence of TMAR >0.35 and TMAOR ≤0.15 was associated with a markedly higher OR (11.16; 95% CI, 5.45 to 22.8), compared with TMAR >0.35 only (OR = 1.71; 95% CI, 0.42 to 6.95) or TMAOR ≤0.15 only (OR = 2.06; 95% CI, 1.09 to 3.90), with a significant additive interaction. However, the mathematical interaction was nonsignificant. Conclusions TMAO metabolites in the early pregnancy were associated with the risk of GDM, whereas TMA was more likely to play a causal role in GDM.

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Are infectious diseases risk factors for sarcoidosis or a result of reverse causation? Findings from a population-based nested case–control study

European Journal of Epidemiology ◽

10.1007/s10654-020-00611-w ◽

2020 ◽

Vol 35 (11) ◽

pp. 1087-1097 ◽

Cited By ~ 3

Author(s):

Marios Rossides ◽

Susanna Kullberg ◽

Johan Askling ◽

Anders Eklund ◽

Johan Grunewald ◽

...

Keyword(s):

Infectious Disease ◽

Infectious Diseases ◽

Case Control Study ◽

Conditional Logistic Regression ◽

Disease Onset ◽

Latency Period ◽

Case Control ◽

Reverse Causation ◽

Nested Case Control ◽

Control Study

AbstractFindings from molecular studies suggesting that several infectious agents cause sarcoidosis are intriguing yet conflicting and likely biased due to their cross-sectional design. As done in other inflammatory diseases to overcome this issue, prospectively-collected register data could be used, but reverse causation is a threat when the onset of disease is difficult to establish. We investigated the association between infectious diseases and sarcoidosis to understand if they are etiologically related. We conducted a nested case–control study (2009–2013) using incident sarcoidosis cases from the Swedish National Patient Register (n = 4075) and matched general population controls (n = 40,688). Infectious disease was defined using inpatient/outpatient visits and/or antimicrobial dispensations starting 3 years before diagnosis/matching. Adjusted odds ratios (aOR) of sarcoidosis were estimated using conditional logistic regression and tested for robustness assuming the presence of reverse causation bias. The aOR of sarcoidosis associated with history of infectious disease was 1.19 (95% confidence interval [CI] 1.09, 1.29; 21% vs. 16% exposed cases and controls, respectively). Upper respiratory and ocular infections conferred the highest OR. Findings were similar when we altered the infection definition or varied the infection-sarcoidosis latency period (1–7 years). In bias analyses assuming one in 10 infections occurred because of preclinical sarcoidosis, the observed association was completely attenuated (aOR 1.02; 95% CI 0.90, 1.15). Our findings, likely induced by reverse causation due to preclinical sarcoidosis, do not support the hypothesis that common symptomatic infectious diseases are etiologically linked to sarcoidosis. Caution for reverse causation bias is required when the real disease onset is unknown.

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Plasma Isoflavones and Subsequent Risk of Prostate Cancer in a Nested Case-Control Study: The Japan Public Health Center

Journal of Clinical Oncology ◽

10.1200/jco.2008.16.8807 ◽

2008 ◽

Vol 26 (36) ◽

pp. 5923-5929 ◽

Cited By ~ 75

Author(s):

Norie Kurahashi ◽

Motoki Iwasaki ◽

Manami Inoue ◽

Shizuka Sasazuki ◽

Shoichiro Tsugane

Keyword(s):

Public Health ◽

Prostate Cancer ◽

Health Center ◽

Case Control Study ◽

Conditional Logistic Regression ◽

Case Control ◽

Conditional Logistic Regression Model ◽

Public Health Center ◽

Nested Case Control ◽

Control Study

PurposeThe incidence of prostate cancer is much lower in Japanese than Western populations. Given the preventive effects of isoflavones on carcinogenesis in the prostate in many nonhuman studies and the high consumption of isoflavones in Japanese, this low incidence may be partly due to the effects of soy.Patients and MethodsWe conducted a nested case-control study within the Japan Public Health Center–based Prospective Study. A total of 14,203 men aged 40 to 69 years who had returned the baseline questionnaire and provided blood samples were observed from 1990 to 2005. During a mean of 12.8 years of follow-up, 201 newly diagnosed prostate cancers were identified. Two matched controls for each case were selected from the cohort. Conditional logistic regression model was used to estimate the odds ratios (ORs) and 95% CIs for prostate cancer in relation to plasma levels of isoflavone.ResultsPlasma genistein level tended to be inversely associated with the risk of total prostate cancer. Although plasma daidzein showed no association, the highest tertile for plasma equol, a metabolite of daidzein, was significantly associated with a decreased risk of total prostate cancer (OR = 0.60; 95% CI, 0.36 to 0.99; Ptrend= .04). These inverse associations were strengthened after analysis was confined to localized cases, with ORs in the highest group of plasma genistein and equol compared with the lowest of 0.54 (95% CI, 0.29 to 1.01; Ptrend= .03) and 0.43 (95% CI, 0.22 to 0.82; Ptrend= .02), respectively. Plasma isoflavone levels were not statistically significantly associated with the risk of advanced prostate cancer.ConclusionIsoflavones may prevent the development of prostate cancer.

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Antibiotic use in children and youths with asthma: a population-based case-control study

ERJ Open Research ◽

10.1183/23120541.00944-2020 ◽

2021 ◽

Vol 7 (1) ◽

pp. 00944-2020

Author(s):

Ivy Fong ◽

Jingqin Zhu ◽

Yaron Finkelstein ◽

Teresa To

Keyword(s):

Case Control Study ◽

Antibiotic Prescription ◽

Conditional Logistic Regression ◽

Antibiotic Use ◽

Population Based ◽

Case Control ◽

Use Patterns ◽

Nested Case Control ◽

Stratified Analysis ◽

Control Study

RationaleAntibiotics are among the most common medications dispensed to children and youths. The objective of this study was to characterise and compare antibiotic use patterns between children and youths with and without asthma.MethodsWe conducted a population-based nested case–control study using health administrative data from Ontario, Canada, in 2018. All Ontario residents aged 5–24 years with asthma were included as cases. Cases were matched to controls with a 1:1 ratio based on age (within 0.5 year), sex and location of residence. Multivariable conditional logistic regression was used to obtain an odds ratio and 95% confidence interval for having filled at least one antibiotic prescription, adjusted for socioeconomic status, rurality, and presence of common infections, allergic conditions and complex chronic conditions.ResultsThe study population included 1 174 424 Ontario children and youths aged 5–24 years. 31% of individuals with asthma and 23% of individuals without asthma filled at least one antibiotic prescription. The odds of having filled at least one antibiotic prescription were 34% higher among individuals with asthma compared to those without asthma (OR 1.34, 95% CI 1.32–1.35). In the stratified analysis, the odds ratios were highest in the youngest group of children studied, aged 5–9 years (OR 1.45, 95% CI 1.41–1.48), and in females (OR 1.36, 95% CI 1.34–1.38).ConclusionAsthma is significantly associated with increased antibiotic use in children and youths. This association is the strongest in younger children and in females.

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Associations of Bisphenol Exposure With The Risk of Gestational Diabetes Mellitus: A Nested Case-Control Study In Guangxi, China

10.21203/rs.3.rs-840656/v1 ◽

2021 ◽

Author(s):

Peng Tang ◽

Jun Liang ◽

Qian Liao ◽

Huishen Huang ◽

Xiaojing Guo ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Case Control Study ◽

Conditional Logistic Regression ◽

Case Control ◽

Negatively Associated ◽

Increased Risk ◽

Nested Case Control ◽

Control Study

Abstract A growing number of epidemiologic studies have estimated the associations between endocrine-disrupting chemicals and gestational diabetes mellitus (GDM). However, reports on the association between bisphenol A (BPA) substitutes and GDM are limited. This investigation aimed to explore the associations of maternal serum BPA, bisphenol B (BPB), bisphenol F (BPF), bisphenol S (BPS), and tetrabromobisphenol A (TBBPA) with the risk of GDM. A nested case-control study was performed among 500 pregnant women. Associations between the serum bisphenol levels and the risk of GDM were assessed by conditional logistic regression analysis and two-mixture modeling approaches (Bayesian kernel machine regression [BKMR] and quantile g-computation). BPA and TBBPA were negatively associated with the risk of GDM in the adjusted models, respectively. Intermediate BPS levels were associated with increased odds (OR: 1.84; 95% CI: 1.04, 3.27) of GDM compared with the low concentration groups only based on the single-bisphenol models. Associations between BPA, BPS, and TBBPA with the risk of GDM were also found in the BKMR analysis. The quantile g-computation (OR: 0.55; 95% CI: 0.43, 0.69) and BKMR models revealed a statistically significant and negative joint effect of the five bisphenols on the risk of GDM. This study demonstrates the association between exposure to BPS with the increased risk of GDM. In addition, exposure to BPA and TBBPA were associated with the reduced risk of GDM. Moreover, exposure to the mixture of the five bisphenols was negatively associated with the risk of GDM.

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