scholarly journals Human Papillomavirus Antibodies and Future Risk of Anogenital Cancer: A Nested Case-Control Study in the European Prospective Investigation Into Cancer and Nutrition Study

2015 ◽  
Vol 33 (8) ◽  
pp. 877-884 ◽  
Author(s):  
Aimée R. Kreimer ◽  
Paul Brennan ◽  
Krystle A. Lang Kuhs ◽  
Tim Waterboer ◽  
Gary Clifford ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Anal Cancer ◽  
Cancer Diagnosis ◽  
Blood Samples ◽  
Hpv16 E6 ◽  
Hpv E6 ◽  
Nutrition Study ◽  
Nested Case Control ◽  
Control Study ◽  
Prospective Investigation

Purpose Human papillomavirus (HPV) type 16 (HPV16) causes cancer at several anatomic sites. In the European Prospective Investigation Into Cancer and Nutrition study, HPV16 E6 seropositivity was present more than 10 years before oropharyngeal cancer diagnosis and was nearly absent in controls. The current study sought to evaluate the extent to which HPV16 E6 antibodies are present before diagnosis of anogenital cancers within the same cohort. Methods Four hundred incident anogenital cancers (273 cervical, 24 anal, 67 vulvar, 12 vaginal, and 24 penile cancers) with prediagnostic blood samples (collected on average 3 and 8 years before diagnosis for cervix and noncervix cancers, respectively) and 718 matched controls were included. Plasma was analyzed for antibodies against HPV16 E6 and multiple other HPV proteins and genotypes and evaluated in relation to risk using unconditional logistic regression. Results HPV16 E6 seropositivity was present in 29.2% of individuals (seven of 24 individuals) who later developed anal cancer compared with 0.6% of controls (four of 718 controls) who remained cancer free (odds ratio [OR], 75.9; 95% CI, 17.9 to 321). HPV16 E6 seropositivity was less common for cancers of the cervix (3.3%), vagina (8.3%), vulva (1.5%), and penis (8.3%). No associations were seen for non–type 16 HPV E6 antibodies, apart from anti-HPV58 E6 and anal cancer (OR, 6.8; 95% CI, 1.4 to 33.1). HPV16 E6 seropositivity tended to increase in blood samples drawn closer in time to cancer diagnosis. Conclusion HPV16 E6 seropositivity is relatively common before diagnosis of anal cancer but rare for other HPV-related anogenital cancers.

scholarly journals Transcriptomic signals in blood prior to lung cancer focusing on time to diagnosis and metastasis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Therese H. Nøst ◽  
Marit Holden ◽  
Tom Dønnem ◽  
Hege Bøvelstad ◽  
Charlotta Rylander ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Diagnosis ◽  
Metastatic Cancer ◽  
Case Control ◽  
Functional Genomic ◽  
Blood Samples ◽  
Lung Cancer Diagnosis ◽  
Time To Diagnosis ◽  
Genomic Signals ◽  
Nested Case Control

AbstractRecent studies have indicated that there are functional genomic signals that can be detected in blood years before cancer diagnosis. This study aimed to assess gene expression in prospective blood samples from the Norwegian Women and Cancer cohort focusing on time to lung cancer diagnosis and metastatic cancer using a nested case–control design. We employed several approaches to statistically analyze the data and the methods indicated that the case–control differences were subtle but most distinguishable in metastatic case–control pairs in the period 0–3 years prior to diagnosis. The genes of interest along with estimated blood cell populations could indicate disruption of immunological processes in blood. The genes identified from approaches focusing on alterations with time to diagnosis were distinct from those focusing on the case–control differences. Our results support that explorative analyses of prospective blood samples could indicate circulating signals of disease-related processes.

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

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.

scholarly journals Viral Load in the Natural History of Human Papillomavirus Type 16 Infection: A Nested Case–Control Study

2011 ◽  
Vol 203 (10) ◽  
pp. 1425-1433 ◽  
Author(s):  
Long Fu Xi ◽  
James P. Hughes ◽  
Philip E. Castle ◽  
Zoe R. Edelstein ◽  
Chunhui Wang ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Viral Load ◽  
Natural History ◽  
Case Control Study ◽  
Case Control ◽  
Human Papillomavirus Type 16 ◽  
History Of ◽  
Nested Case Control ◽  
Control Study

scholarly journals The High-Risk Human Papillomavirus Type 16 E6 Counters the GAP Function of E6TP1 toward Small Rap G Proteins

2003 ◽  
Vol 77 (2) ◽  
pp. 1614-1620 ◽  
Author(s):  
Latika Singh ◽  
Qingshen Gao ◽  
Ajay Kumar ◽  
Takaya Gotoh ◽  
David E. Wazer ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
G Protein ◽  
Mutational Analysis ◽  
Protein Signaling ◽  
Hpv16 E6 ◽  
Human Papillomavirus Type 16 ◽  
Hpv E6 ◽  
Small G Protein ◽  
Transforming Activity

ABSTRACT We have recently identified E6TP1 (E6-targeted protein 1) as a novel high-risk human papillomavirus type 16 (HPV16) E6-binding protein. Importantly, mutational analysis of E6 revealed a strong correlation between the transforming activity and its abilities to bind and target E6TP1 for ubiquitin-mediated degradation. As a region within E6TP1 has high homology with GAP domains of known and putative Rap GTPase-activating proteins (GAPs), these results raised the possibility that HPV E6 may alter the Rap small-G-protein signaling pathway. Using two different approaches, we now demonstrate that human E6TP1 exhibits GAP activity for Rap1 and Rap2, confirming recent findings that a closely related rat homologue exhibits Rap-specific GAP activity. Using mutational analysis, we localize the GAP activity to residues 240 to 945 of E6TP1. Significantly, we demonstrate that coexpression of HPV16 E6, by promoting the degradation of E6TP1, enhances the GTP loading of Rap. These results support a role of Rap small-G-protein pathway in E6-mediated oncogenesis.

The association between proton pump inhibitors (PPI) use for gastro-esophageal reflux disease (GERD) and lung cancer (LC): A nested case-control study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1562-1562
Author(s):  
Hadas Dresler ◽  
Daniel Keizman ◽  
Ronac Mamtani ◽  
Maya Gottfried ◽  
Natalie Maimon ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Risk ◽  
Cancer Diagnosis ◽  
Case Control Study ◽  
Lung Cancer Risk ◽  
Case Control ◽  
Sensitivity Analyses ◽  
Diagnostic Code ◽  
Nested Case Control ◽  
Control Study

1562 Background: Data suggests that GERD with recurrent reflux and microaspiration of stomach contents, may be associated with lung injury, inflammation, activation of proliferative signals, and eventually DNA damage and malignant transformation. Recently, a large population based cohort study found that GERD may increase the risk of lung cancer in Asians. In the present nested case control study, we aimed to evaluate the association between PPI use as a surrogate for GERD and lung cancer in a large western population. Methods: We conducted a matched case-control study within a population-representative database from the United Kingdom. Study cases were defined as individuals with any diagnostic code of lung cancer. For every case, four eligible controls were matched on age, gender, practice site, time and duration of follow-up. Exposure of interest was PPI use prior to cancer diagnosis. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer were estimated using conditional logistic regression. Adjustment was performed for smoking. Results: The study population included 19143 lung cancer cases and 74473 matched controls. PPI use was associated with a significantly increased lung cancer risk (adjusted OR 1.70, 95%CI 1.64-1.77, p < 0.001). In a sensitivity analyses we observed similar associations when PPI use was initiated more than one year prior to cancer diagnosis (adjusted OR 1.18, 95%CI 1.13-1.23, p < 0.001) and more than two years prior to cancer diagnosis (adjusted OR 1.15, 95%CI 1.10-1.20, p < 0.001) Conclusions: ChronicPPI use, as a surrogate for symptomatic GERD, may be associated with a higher lung cancer risk.

scholarly journals NFX1 Plays a Role in Human Papillomavirus Type 16 E6 Activation of NFκB Activity

2010 ◽  
Vol 84 (21) ◽  
pp. 11461-11469 ◽  
Author(s):  
Mei Xu ◽  
Rachel A. Katzenellenbogen ◽  
Carla Grandori ◽  
Denise A. Galloway
Keyword(s):  
Human Papillomavirus ◽  
Human Telomerase Reverse Transcriptase ◽  
Hpv16 E6 ◽  
Regulatory Pathways ◽  
Cellular Processes ◽  
Hpv E6 ◽  
Host Cell Interactions ◽  
Nfκb Pathway ◽  
Human Telomerase ◽  
Dual Regulator

ABSTRACT High-risk human papillomavirus (HR HPV) requires differentiating epithelial cells to continue to divide in order to replicate the viral DNA. To achieve this, HPV perturbs several regulatory pathways, including cellular apoptosis and senescence signals. HPV E6 has been identified as a regulator of the NFκB signaling pathway, a pathway important in many cellular processes, as well as regulation of virus-host cell interactions. We report here that NFX1-91, an endogenously expressed transcriptional regulator of human telomerase reverse transcriptase (hTERT) that is targeted by HPV type 16 (HPV16) E6/E6-associated protein (E6AP) for degradation, is also critical for regulation of the NFκB pathway by HPV16 E6. Microarray analysis revealed induction of NFκB-responsive genes and reduction of NFκB inhibitors with knockdown of NFX1-91. Knockdown of NFX1-91 induced downregulation of p105, an NFκB inhibitor in both primary human foreskin keratinocytes (HFKs) and HCT116 cells. Chromatin immunoprecipitation assays further confirmed that NFX1-91 bound to the p105 promoter and upregulated its expression. Similarly, in HPV16 E6-positive cells, reduction of p105 expression was observed, paralleling knockdown of NFX1-91 expression. Overall, our data suggest a mechanism for HPV16 E6 activation of the NFκB pathway through NFX1-91. Also, it provides evidence that NFX1-91 can function as a dual regulator, not only a transcriptional repressor, but also a transcriptional activator, when bound to DNA.

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