Serum IGFBP-2 and Risk of Atypical Hyperplasia of the Breast

Atypical hyperplasia of the breast (AH) is associated with increased risk of subsequent invasive breast cancer, yet little is known about the etiology of AH. Insulin-like growth factor binding protein 2 (IGFBP-2) may contribute to the development of AH due to its proliferative effects on mammary tissue. We conducted a nested case-control study of postmenopausal women enrolled in Women’s Health Initiative-Clinical Trial. Cases were 275 women who developed incident AH during follow-up, individually (1 : 1) matched to controls. Levels of IGFBP-2 were determined from fasting serum collected at baseline. Multivariable conditional logistic regression models were used to estimate odds ratios for the association of IGFBP-2 with risk of AH. Serum IGFBP-2 was associated with a nonsignificant decrease in risk for AH, when comparing the highest quartile to lowest quartile (OR = 0.65; 95% CI = 0.32–1.31). This decrease in risk was most evident when analyses were restricted to nondiabetic, nonusers of hormone therapy (OR = 0.33, 95% CI = 0.13–0.86,ptrend= 0.06) and nondiabetic women who were overweight or obese (OR = 0.43, 95% CI = 0.18–1.03,ptrend= 0.05). Results from this study provide some support for an inverse association between serum IGFBP2 levels and risk of AH, particularly in nondiabetic women who are overweight or obese. Further studies are required to confirm these results.

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Anti-TNF Therapy and the Risk of Herpes Zoster Among Patients With Inflammatory Bowel Disease

Inflammatory Bowel Diseases ◽

10.1093/ibd/izab092 ◽

2021 ◽

Author(s):

Christina Santella ◽

Alain Bitton ◽

Christopher Filliter ◽

Talat Bessissow ◽

Maria Vutcovici ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Herpes Zoster ◽

Bowel Disease ◽

Conditional Logistic Regression ◽

Increased Risk ◽

Inflammatory Bowel ◽

Nested Case Control ◽

Incident Cases ◽

Control Study

Abstract Background The specific contribution of anti-TNF therapy to the onset of herpes zoster (HZ) in patients with inflammatory bowel disease (IBD) remains uncertain. Thus, the purpose of this nested case-control study was to explore whether the use of anti-TNF therapy is associated with an increased risk of HZ. Methods Using the Regie de l’Assurance Maladie du Québec, we identified incident cases of IBD between 1998 and 2015. We matched IBD cases of HZ with up to 10 IBD HZ-free controls on year of cohort entry and follow-up. Current use was defined as a prescription for anti-TNF therapy 60 days before the index date, with nonuse as the comparator. We conducted conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs), adjusting for potential confounders. Results The cohort consisted of 15,454 incident IBD patients. Over an average follow-up of 5.0 years, 824 patients were diagnosed with HZ (incidence of 9.3 per 1000 person-years). Relative to nonuse, current use of anti-TNF therapy was associated with an overall increased risk of HZ (OR, 1.5; 95% CI, 1.1–2.1). The risk was increased among those older than 50 years (OR, 2.1; 95% CI, 1.2–3.6) and those additionally using steroids and immunosuppressants (OR, 4.1; 95% CI, 2.3–7.2). Conclusions Use of anti-TNF therapy was associated with an increased risk of HZ among patients with IBD, particularly among those older than 50 years and those on combination therapy. Prevention strategies for HZ ought to be considered for younger IBD patients commencing treatment.

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Pre-diagnostic leukocyte mitochondrial DNA copy number and colorectal cancer risk

Carcinogenesis ◽

10.1093/carcin/bgz159 ◽

2019 ◽

Vol 40 (12) ◽

pp. 1462-1468 ◽

Cited By ~ 4

Author(s):

Keming Yang ◽

Xin Li ◽

Michele R Forman ◽

Patrick O Monahan ◽

Bret H Graham ◽

...

Keyword(s):

Colorectal Cancer ◽

Mitochondrial Dna ◽

Copy Number ◽

Quantitative Polymerase Chain Reaction ◽

Conditional Logistic Regression ◽

Experimental Studies ◽

Inverse Association ◽

Mitochondrial Dna Copy Number ◽

Increased Risk

Abstract Mitochondrial DNA (mtDNA) is susceptible to oxidative stress and mutation. Few epidemiological studies have assessed the relationship between mtDNA copy number (mtDNAcn) and risk of colorectal cancer (CRC), with inconsistent findings. In this study, we examined the association between pre-diagnostic leukocyte mtDNAcn and CRC risk in a case–control study of 324 female cases and 658 matched controls nested within the Nurses’ Health Study (NHS). Relative mtDNAcn in peripheral blood leukocytes was measured by quantitative polymerase chain reaction-based assay. Conditional logistic regression models were applied to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association of interest. Results showed lower log-mtDNAcn was significantly associated with increased risk of CRC, in a dose-dependent relationship (P for trend < 0.0001). Compared to the fourth quartile, multivariable-adjusted OR [95% confidence interval (CI)] was 1.10 (0.69, 1.76) for the third quartile, 1.40 (0.89, 2.19) for the second quartile and 2.19 (1.43, 3.35) for the first quartile. In analysis by anatomic subsite of CRC, we found a significant inverse association for proximal colon cancer [lowest versus highest quartile, multivariable-adjusted OR (95% CI) = 3.31 (1.70, 6.45), P for trend = 0.0003]. Additionally, stratified analysis according to the follow-up time since blood collection showed that the inverse association between mtDNAcn and CRC remained significant among individuals with ≥ 5 years’ follow-up, and marginally significant among those with ≥ 10 years’ follow-up since mtDNAcn testing, suggesting that mtDNAcn may serve as a long-term predictor for risk of CRC. In conclusion, pre-diagnostic leukocyte mtDNAcn was inversely associated with CRC risk. Further basic experimental studies are needed to explore the underlying biological mechanisms linking mtDNAcn to CRC carcinogenesis.

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Does Flipping the Tubercle for Improved Cartilage Repair Exposure Increase the Risk for Arthrofibrosis?

Cartilage ◽

10.1177/1947603520968209 ◽

2020 ◽

pp. 194760352096820

Author(s):

Gergo Merkely ◽

Jakob Ackermann ◽

Emily Sheehy ◽

Andreas H. Gomoll

Keyword(s):

Logistic Regression ◽

Cartilage Repair ◽

Regression Models ◽

Case Control Study ◽

Level Of Evidence ◽

Logistic Regression Models ◽

Increased Risk ◽

Repair Procedure ◽

Control Study

Objective We sought to determine whether rates of postoperative arthrofibrosis following tibial tuberosity osteotomy (TTO) with complete mobilization of the fragment (TTO-HD) are comparable to TTOs where the hinge remained intact (TTO-HI). Design Patients who underwent TTO with concomitant cartilage repair procedure between January 2007 and May 2017, with at least 2 years of follow-up were included in this study. Postoperative reinterventions following TTO-HD and TTO-HI were assessed and multivariant logistic regression models were used to identify whether postoperative reinterventions can be attributed to either technique when controlled for defect size or defect number. Results A total of 127 patients (TTO-HD, n = 80; TTO-HI, n = 47) were included in this study. Significantly more patients in the TTO-HD group (31.2%) developed postoperative arthrofibrosis compared with TTO-HI (6.4%; P < 0.05). Multivariant logistic regression revealed that TTO-HD is an independent risk factor for predicting postoperative arthrofibrosis (OR 6.5, CI = 1.7-24.2, P < 0.05). Conclusion Patients who underwent TTO with distal hinge detachment and a proximally flipped tubercle for better exposure during concomitant cartilage repair were at a significantly higher risk of postoperative arthrofibrosis than patients with similar size and number of defects treated without mobilization of the tubercle. While certain procedures can benefit from larger exposure, surgeons should be aware of the increased risk of postoperative arthrofibrosis. Level of Evidence Level III, case-control study.

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Blood polyphenol concentrations and differentiated thyroid carcinoma in women from the European Prospective Investigation into Cancer and Nutrition (EPIC) study

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqaa277 ◽

2020 ◽

Vol 113 (1) ◽

pp. 162-171

Author(s):

Raul Zamora-Ros ◽

Leila Lujan-Barroso ◽

David Achaintre ◽

Silvia Franceschi ◽

Cecilie Kyrø ◽

...

Keyword(s):

Multiple Testing ◽

Conditional Logistic Regression ◽

Differentiated Thyroid Carcinoma ◽

Blood Concentrations ◽

Logistic Regression Models ◽

Not Otherwise Specified ◽

Ferulic Acids ◽

Nested Case Control ◽

Control Study ◽

Prospective Investigation

ABSTRACT Background Polyphenols are natural compounds with anticarcinogenic properties in cellular and animal models, but epidemiological evidence determining the associations of these compounds with thyroid cancer (TC) is lacking. Objectives The aim of this study was to evaluate the relations between blood concentrations of 36 polyphenols and TC risk in EPIC (the European Prospective Investigation into Cancer and Nutrition). Methods A nested case–control study was conducted on 273 female cases (210 papillary, 45 follicular, and 18 not otherwise specified TC tumors) and 512 strictly matched controls. Blood polyphenol concentrations were analyzed by HPLC coupled to tandem MS after enzymatic hydrolysis. Results Using multivariable-adjusted conditional logistic regression models, caffeic acid (ORlog2: 0.55; 95% CI: 0.33, 0.93) and its dehydrogenated metabolite, 3,4-dihydroxyphenylpropionic acid (ORlog2: 0.84; 95% CI: 0.71, 0.99), were inversely associated with differentiated TC risk. Similar results were observed for papillary TC, but not for follicular TC. Ferulic acid was also inversely associated only with papillary TC (ORlog2: 0.68; 95% CI: 0.51, 0.91). However, none of these relations was significant after Bonferroni correction for multiple testing. No association was observed for any of the remaining polyphenols with total differentiated, papillary, or follicular TC. Conclusions Blood polyphenol concentrations were mostly not associated with differentiated TC risk in women, although our study raises the possibility that high blood concentrations of caffeic, 3,4-dihydroxyphenylpropionic, and ferulic acids may be related to a lower papillary TC risk.

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Exposure to airborne cadmium and breast cancer stage, grade and histology at diagnosis: findings from the E3N cohort study

Scientific Reports ◽

10.1038/s41598-021-01243-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Amina Amadou ◽

Delphine Praud ◽

Thomas Coudon ◽

Aurélie M. N. Danjou ◽

Elodie Faure ◽

...

Keyword(s):

Breast Cancer ◽

Conditional Logistic Regression ◽

Positive Association ◽

Cadmium Exposure ◽

Tubular Carcinoma ◽

Logistic Regression Models ◽

Increased Risk ◽

Estrogenic Properties ◽

Nested Case Control

AbstractMolecular studies suggest that cadmium due to its estrogenic properties, might play a role in breast cancer (BC) progression. However epidemiological evidence is limited. This study explored the association between long-term exposure to airborne cadmium and risk of BC by stage, grade of differentiation, and histological types at diagnosis. A nested case–control study of 4401 cases and 4401 matched controls was conducted within the French E3N cohort. A Geographic Information System (GIS)-based metric demonstrated to reliably characterize long-term environmental exposures was employed to evaluate airborne exposure to cadmium. Multivariable adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression models. There was no relationship between cadmium exposure and stage of BC. Also, no association between cadmium exposure and grade of differentiation of BC was observed. However, further analyses by histological type suggested a positive association between cadmium and risk of invasive tubular carcinoma (ITC) BC [ORQ5 vs Q1 = 3.4 (95% CI 1.1–10.7)]. The restricted cubic spline assessment suggested a dose–response relationship between cadmium and ITC BC subtype. Our results do not support the hypothesis that airborne cadmium exposure may play a role in advanced BC risk, but suggest that cadmium may be associated with an increased risk of ITC.

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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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Children’s erythrocyte fatty acids are associated with the risk of islet autoimmunity

Scientific Reports ◽

10.1038/s41598-021-82200-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sari Niinistö ◽

◽

Iris Erlund ◽

Hye-Seung Lee ◽

Ulla Uusitalo ◽

...

Keyword(s):

Fatty Acids ◽

Conditional Logistic Regression ◽

Docosapentaenoic Acid ◽

Monounsaturated Fatty Acids ◽

Islet Autoimmunity ◽

Logistic Regression Models ◽

High Genetic Risk ◽

Increased Risk ◽

And Gender ◽

Nested Case Control

AbstractOur aim was to investigate the associations between erythrocyte fatty acids and the risk of islet autoimmunity in children. The Environmental Determinants of Diabetes in the Young Study (TEDDY) is a longitudinal cohort study of children at high genetic risk for type 1 diabetes (n = 8676) born between 2004 and 2010 in the U.S., Finland, Sweden, and Germany. A nested case–control design comprised 398 cases with islet autoimmunity and 1178 sero-negative controls matched for clinical site, family history, and gender. Fatty acids composition was measured in erythrocytes collected at the age of 3, 6, and 12 months and then annually up to 6 years of age. Conditional logistic regression models were adjusted for HLA risk genotype, ancestry, and weight z-score. Higher eicosapentaenoic and docosapentaenoic acid (n − 3 polyunsaturated fatty acids) levels during infancy and conjugated linoleic acid after infancy were associated with a lower risk of islet autoimmunity. Furthermore, higher levels of some even-chain saturated (SFA) and monounsaturated fatty acids (MUFA) were associated with increased risk. Fatty acid status in early life may signal the risk for islet autoimmunity, especially n − 3 fatty acids may be protective, while increased levels of some SFAs and MUFAs may precede islet autoimmunity.

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Pre-Diagnostic Circulating Metabolites and Colorectal Cancer Risk in the Cancer Prevention Study-II Nutrition Cohort

Metabolites ◽

10.3390/metabo11030156 ◽

2021 ◽

Vol 11 (3) ◽

pp. 156

Author(s):

Marjorie L. McCullough ◽

Rebecca A. Hodge ◽

Peter T. Campbell ◽

Victoria L. Stevens ◽

Ying Wang

Keyword(s):

Colorectal Cancer ◽

Cancer Risk ◽

Cancer Prevention ◽

Conditional Logistic Regression ◽

Colorectal Cancer Risk ◽

Prevention Study ◽

Blood Draw ◽

Logistic Regression Models ◽

Nested Case Control ◽

Control Study

Untargeted metabolomic studies have identified potential biomarkers of colorectal cancer risk, but evidence is still limited and broadly inconsistent. Among 39,239 Cancer Prevention Study II Nutrition cohort participants who provided a blood sample between 1998–2001, 517 newly diagnosed colorectal cancers were identified through 30 June 2015. In this nested case–control study, controls were matched 1:1 to cases on age, sex, race and date of blood draw. Mass spectroscopy-based metabolomic analyses of pre-diagnostic plasma identified 886 named metabolites, after quality control exclusions. Conditional logistic regression models estimated multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI) for 1 standard deviation (SD) increase in each metabolite with risk of colorectal cancer. Six metabolites were associated with colorectal cancer risk at a false discovery rate < 0.20. These metabolites were of several classes, including cofactors and vitamins, nucleotides, xenobiotics, lipids and amino acids. Five metabolites (guanidinoacetate, 2’-O-methylcytidine, vanillylmandelate, bilirubin (E,E) and N-palmitoylglycine) were positively associated (OR per 1 SD = 1.29 to 1.32), and one (3-methylxanthine) was inversely associated with CRC risk (OR = 0.79, 95% CI, 0.69–0.89). We did not replicate findings from two earlier prospective studies of 250 cases each after adjusting for multiple comparisons. Large pooled prospective analyses are warranted to confirm or refute these findings and to discover and replicate metabolites associated with colorectal cancer risk.

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Recurring Gastrointestinal Infections Increase the Risk of Dementia

Journal of Alzheimer s Disease ◽

10.3233/jad-210316 ◽

2021 ◽

pp. 1-10

Author(s):

Anne Fink ◽

Gabriele Doblhammer ◽

Gültekin Tamgüney

Keyword(s):

Conditional Logistic Regression ◽

Case Control ◽

Health Claims ◽

Gastrointestinal Infections ◽

Increased Risk ◽

Health Claims Data ◽

Nested Case Control ◽

Significant Health ◽

Control Study

Background: Gastrointestinal infections cause significant health problems, including those affecting the immune, musculoskeletal, and nervous system, and are one of the leading causes for death worldwide. Recent findings suggest that microbiota of the gastrointestinal tract contribute to dementia. Objective: In this nested case-control study we investigated the role of common gastrointestinal infections on the subsequent risk of dementia. Methods: We used a longitudinal sample of 202,806 individuals from health claims data of the largest German health insurer and applied a nested case-control design with 23,354 initial dementia cases between 2006 and 2014 and 23,354 matched controls. We used conditional logistic regression to compute odds ratios (ORs) for dementia and corresponding 95%confidence intervals (CIs), adjusting for potential confounders. Results: The risk of dementia was increased in patients with recurring incidences of quarters with diagnosed gastrointestinal infections when compared to the unexposed population (one quarter: OR = 1.49, 95%CI = 1.40–1.58; two quarters: OR = 1.70, 95%CI = 1.51–1.91; three or more quarters: OR = 1.64, 95%CI = 1.40–1.93), adjusted for potential confounders. Conclusion: Our findings suggest that recurring gastrointestinal infections are associated with an increased risk of subsequent dementia.

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Evaluation of the Catalan Physical Activity, Sports and Health Plan: a nested case-control study

European Journal of Public Health ◽

10.1093/eurpub/ckaa090 ◽

2020 ◽

Vol 30 (6) ◽

pp. 1084-1090

Author(s):

Jakob Weitzer ◽

Angelina Gonzalez-Viana ◽

Santiago Pérez-Hoyos ◽

Ermengol Coma ◽

Leonardo Mendez ◽

...

Keyword(s):

Physical Activity ◽

Health Plan ◽

Conditional Logistic Regression ◽

Real Life ◽

Modern Society ◽

Case Control ◽

Lower Probability ◽

Nested Case Control ◽

Control Study

Abstract Background Physical inactivity is one of the most important risk factors in modern society. Primary Health Care (PHC) interventions have been shown to be effective to increase physical activity (PA). This work evaluates the Catalan Physical Activity, Sport and Health Plan (PAFES). Methods Nested case–control design with risk-set matching based on a retrospective cohort of 22 450 physically inactive people registered between 2010 and 2018 in the Catalan electronic medical record (EMR). Confounder adjusted conditional logistic regression was used to estimate the probability that participants who had received PA advice became active between 2010 and 2018 compared to those who did not receive it. Results A lower probability to become active [odds ratio (OR) = 0.11, 95% confidence interval (CI) 0.10–0.13] was found for those people who had received PA advice only once. However, the probability to become active increased for people who had received advice two or more times (two times: OR = 1.43, 95% CI 1.32–1.55). A dose–response relationship was observed. Conclusions This is the first study evaluating a PA promotion real-life intervention in PHC using a large cohort based on data from an EMR with more than 2 years of follow-up.

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