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Article ; Online: A panel of hepatitis C virus glycoproteins for the characterization of antibody responses using antibodies with diverse recognition and neutralization patterns.

Chumbe, Ana / Grobben, Marloes / Capella-Pujol, Joan / Koekkoek, Sylvie M / Zon, Ian / Slamanig, Stefan / Merat, Sabrina J / Beaumont, Tim / Sliepen, Kwinten / Schinkel, Janke / van Gils, Marit J

Virus research

2024 Volume 341, Page(s) 199308

Abstract: A vaccine against Hepatitis C virus (HCV) is urgently needed to limit the spread of HCV. The large ...

Abstract	A vaccine against Hepatitis C virus (HCV) is urgently needed to limit the spread of HCV. The large antigenic diversity of the HCV glycoprotein E1E2 makes it difficult to design a vaccine but also to fully understand the antibody response after infection or vaccination. Here we designed a panel of HCV pseudoparticles (HCVpps) that cover a wide range of genetically and antigenically diverse E1E2s. We validate our panel using neutralization and a binding antibody multiplex assay (BAMA). The panel of HCVpps includes E1E2 glycoproteins from acute and chronically infected cases in the Netherlands, as well as E1E2 glycoproteins from previously reported HCVs. Using eight monoclonal antibodies targeting multiple antigenic regions on E1E2, we could categorize four groups of neutralization sensitive viruses with viruses showing neutralization titers over a 100-fold range. One HCVpp (AMS0230) was extremely neutralization resistant and only neutralized by AR4-targeting antibodies. In addition, using binding antibody multiplex competition assay, we delineated mAb epitopes and their interactions. The binding and neutralization sensitivity of the HCVpps were confirmed using patient sera. At the end, eleven HCVpps with unique antibody binding and neutralization profiles were selected as the final panel for standardized HCV antibody assessments. In conclusion, this HCVpp panel can be used to evaluate antibody binding and neutralization breadth and potency as well as delineate the epitopes targeted in sera from patients or candidate vaccine trials. The HCVpp panel in combination with the established antibody competition assay present highly valuable tools for HCV vaccine development and evaluation.
MeSH term(s)	Humans ; Hepacivirus ; Antibodies, Neutralizing ; Antibody Formation ; Neutralization Tests ; Viral Envelope Proteins ; Hepatitis C ; Glycoproteins ; Epitopes ; Hepatitis C Antibodies ; Antibodies, Monoclonal ; Vaccines
Chemical Substances	Antibodies, Neutralizing ; Viral Envelope Proteins ; Glycoproteins ; Epitopes ; Hepatitis C Antibodies ; Antibodies, Monoclonal ; Vaccines
Language	English
Publishing date	2024-01-11
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	605780-9
ISSN	1872-7492 ; 0168-1702
ISSN (online)	1872-7492
ISSN	0168-1702
DOI	10.1016/j.virusres.2024.199308
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Article ; Online: Optimization of the pseudoparticle system for standardized assessments of neutralizing antibodies against hepatitis C virus.

Chumbe, Ana / Urbanowicz, Richard A / Sliepen, Kwinten / Koekkoek, Sylvie M / Molenkamp, Richard / Tarr, Alexander W / Ball, Jonathan K / Schinkel, Janke / van Gils, Marit J

The Journal of general virology

2022 Volume 103, Issue 11

Abstract: ... on disease progression and reinfection is necessary for the development of a protective hepatitis C virus (HCV) vaccine ...

Abstract	A better understanding of the antibody response during natural infection and the effect on disease progression and reinfection is necessary for the development of a protective hepatitis C virus (HCV) vaccine. The HCV pseudoparticle (HCVpp) system enables the study of viral entry and inhibition by antibody neutralization. A robust and comparable neutralization assay is crucial for the development and evaluation of experimental vaccines.With the aim of optimizing the HCVpp-murine leukaemia virus (MLV) system, we tested the neutralization of HCVpp-harbouring E1E2 from 21 HCV isolates representing 6 different genotypes by several monoclonal antibodies (mAbs). HCVpps are generated by expressing functional envelope glycoproteins (E1E2) onto pseudoparticles derived from env-deleted MLV. Adjustments of E1E2, gag-pol and luciferase plasmid ratios resulted in increased yields for most HCVpps and recovery of one non-infectious HCVpp. We simplified and improved the protocol to achieve higher signal/noise ratios and minimized the amount of HCVpps and mAbs needed for the detection of neutralization. Using our optimized protocol, we demonstrated comparable results to previously reported data with both diluted and freeze-thawed HCVpps.In conclusion, we successfully established a simplified and reproducible HCVpp neutralization protocol for studying a wide range of HCV variants. This simplified protocol provides highly consistent results and could be easily adopted by others to evaluate precious biological material. This will contribute to a better understanding of the antibody response during natural infection and help evaluate experimental HCV vaccines.
MeSH term(s)	Animals ; Mice ; Hepacivirus ; Antibodies, Neutralizing ; Hepatitis C Antibodies ; Neutralization Tests ; Viral Envelope Proteins/genetics ; Hepatitis C/genetics ; Antibodies, Monoclonal ; Vaccines
Chemical Substances	Antibodies, Neutralizing ; Hepatitis C Antibodies ; Viral Envelope Proteins ; Antibodies, Monoclonal ; Vaccines
Language	English
Publishing date	2022-12-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	219316-4
ISSN	1465-2099 ; 0022-1317
ISSN (online)	1465-2099
ISSN	0022-1317
DOI	10.1099/jgv.0.001801
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Article ; Online: Induction of cross-neutralizing antibodies by a permuted hepatitis C virus glycoprotein nanoparticle vaccine candidate.

Nature communications

2022 Volume 13, Issue 1, Page(s) 7271

Abstract: Hepatitis C virus (HCV) infection affects approximately 58 million people and causes ~300,000 ...

Abstract	Hepatitis C virus (HCV) infection affects approximately 58 million people and causes ~300,000 deaths yearly. The only target for HCV neutralizing antibodies is the highly sequence diverse E1E2 glycoprotein. Eliciting broadly neutralizing antibodies that recognize conserved cross-neutralizing epitopes is important for an effective HCV vaccine. However, most recombinant HCV glycoprotein vaccines, which usually include only E2, induce only weak neutralizing antibody responses. Here, we describe recombinant soluble E1E2 immunogens that were generated by permutation of the E1 and E2 subunits. We displayed the E2E1 immunogens on two-component nanoparticles and these nanoparticles induce significantly more potent neutralizing antibody responses than E2. Next, we generated mosaic nanoparticles co-displaying six different E2E1 immunogens. These mosaic E2E1 nanoparticles elicit significantly improved neutralization compared to monovalent E2E1 nanoparticles. These results provide a roadmap for the generation of an HCV vaccine that induces potent and broad neutralization.
MeSH term(s)	Humans ; Hepacivirus/genetics ; Antibodies, Neutralizing ; Broadly Neutralizing Antibodies ; Viral Envelope Proteins ; Hepatitis C Antibodies ; Hepatitis C ; Glycoproteins ; Nanoparticles ; Vaccines
Chemical Substances	Antibodies, Neutralizing ; Broadly Neutralizing Antibodies ; Viral Envelope Proteins ; Hepatitis C Antibodies ; Glycoproteins ; Vaccines
Language	English
Publishing date	2022-11-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-34961-8
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Article ; Online: Signatures of V H 1-69-derived hepatitis C virus neutralizing antibody precursors defined by binding to envelope glycoproteins

Joan Capella-Pujol / Marlon de Gast / Laura Radić / Ian Zon / Ana Chumbe / Sylvie Koekkoek / Wouter Olijhoek / Janke Schinkel / Marit J. van Gils / Rogier W. Sanders / Kwinten Sliepen

Nature Communications, Vol 14, Iss 1, Pp 1-

2023 Volume 16

Abstract: Abstract An effective preventive vaccine for hepatitis C virus (HCV) remains a major unmet need ...

Abstract	Abstract An effective preventive vaccine for hepatitis C virus (HCV) remains a major unmet need. Antigenic region 3 (AR3) on the E1E2 envelope glycoprotein complex overlaps with the CD81 receptor binding site and represents an important epitope for broadly neutralizing antibodies (bNAbs) and is therefore important for HCV vaccine design. Most AR3 bNAbs utilize the V H 1-69 gene and share structural features that define the AR3C-class of HCV bNAbs. In this work, we identify recombinant HCV glycoproteins based on a permuted E2E1 trimer design that bind to the inferred V H 1-69 germline precursors of AR3C-class bNAbs. When presented on nanoparticles, these recombinant E2E1 glycoproteins efficiently activate B cells expressing inferred germline AR3C-class bNAb precursors as B cell receptors. Furthermore, we identify critical signatures in three AR3C-class bNAbs that represent two subclasses of AR3C-class bNAbs that will allow refined protein design. These results provide a framework for germline-targeting vaccine design strategies against HCV.
Keywords	Science ; Q
Subject code	570
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
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Article ; Online: Validation of the AUDIT and AUDIT-C for Hazardous Drinking in Community-Dwelling Older Adults.

van Gils, Yannic / Franck, Erik / Dierckx, Eva / van Alphen, Sebastiaan P J / Saunders, John B / Dom, Geert

International journal of environmental research and public health

2021 Volume 18, Issue 17

Abstract: ... Disorders Identification Test (AUDIT) and its abbreviated form, the AUDIT-C. The aim of the present study is ... defined as drinking >10 units/week. Receiver operating characteristics (ROC) curves of AUDIT and AUDIT-C ... values respectively of 80.7% and 81.3% and in women 100% and 71.7%, respectively. We found the AUDIT-C ...

Abstract	Background: One of the best-known tools in screening for hazardous drinking is the Alcohol Use Disorders Identification Test (AUDIT) and its abbreviated form, the AUDIT-C. The aim of the present study is to determine the cut-offs of both instruments in identifying hazardous drinking in older adults. Method: A sample of 1577 older adults completed a questionnaire regarding alcohol behavior. Hazardous drinking was defined as drinking >10 units/week. Receiver operating characteristics (ROC) curves of AUDIT and AUDIT-C were calculated and cut-off scores were derived. Results: Respectively 27.3% and 12.3% of older men and women drank >10 units/week. For the AUDIT the best trade-off between sensitivity and specificity was using a cut-off of ≥5 for men and ≥4 for women, which yielded in men sensitivity and specificity values respectively of 80.7% and 81.3% and in women 100% and 71.7%, respectively. We found the AUDIT-C to perform well with an optimal cut-off of ≥5 for men and ≥4 for women, which generated in men sensitivity and specificity values respectively of 76.5% and 85.3% and in women 100% and 74.1%, respectively. Conclusion: The AUDIT-C is accurate and sufficient in screening for hazardous drinking in community-dwelling older adults if the cut-offs are tailored by gender.
MeSH term(s)	Aged ; Alcoholism ; Female ; Humans ; Independent Living ; Male ; Mass Screening ; Sensitivity and Specificity ; Surveys and Questionnaires
Language	English
Publishing date	2021-09-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2175195-X
ISSN	1660-4601 ; 1661-7827
ISSN (online)	1660-4601
ISSN	1661-7827
DOI	10.3390/ijerph18179266
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Article ; Online: High Levels of C-Reactive Protein Are Associated with an Increased Risk of Ovarian Cancer: Results from the Ovarian Cancer Cohort Consortium.

Peres, Lauren C / Mallen, Adrianne R / Townsend, Mary K / Poole, Elizabeth M / Trabert, Britton / Allen, Naomi E / Arslan, Alan A / Dossus, Laure / Fortner, Renée T / Gram, Inger T / Hartge, Patricia / Idahl, Annika / Kaaks, Rudolf / Kvaskoff, Marina / Magliocco, Anthony M / Merritt, Melissa A / Quirós, J Ramón / Tjonneland, Anne / Trichopoulou, Antonia /

Tumino, Rosario / van Gils, Carla H / Visvanathan, Kala / Wentzensen, Nicolas / Zeleniuch-Jacquotte, Anne / Tworoger, Shelley S

Cancer research

2019 Volume 79, Issue 20, Page(s) 5442–5451

Abstract: ... carcinogenesis. An association between a circulating marker of inflammation, C-reactive protein (CRP), and ...

Abstract	Growing epidemiologic evidence supports chronic inflammation as a mechanism of ovarian carcinogenesis. An association between a circulating marker of inflammation, C-reactive protein (CRP), and ovarian cancer risk has been consistently observed, yet, potential heterogeneity of this association by tumor and patient characteristics has not been adequately explored. In this study, we pooled data from case-control studies nested within six cohorts in the Ovarian Cancer Cohort Consortium (OC3) to examine the association between CRP and epithelial ovarian cancer risk overall, by histologic subtype and by participant characteristics. CRP concentrations were measured from prediagnosis serum or plasma in 1,091 cases and 1,951 controls. Multivariable conditional logistic regression was used to estimate ORs and 95% confidence intervals (CI). When CRP was evaluated using tertiles, no associations with ovarian cancer risk were observed. A 67% increased ovarian cancer risk was found for women with CRP concentrations >10 mg/L compared with <1 mg/L (OR = 1.67; 95% CI = 1.12-2.48). A CRP concentration >10 mg/L was positively associated with risk of mucinous (OR = 9.67; 95% CI = 1.10-84.80) and endometrioid carcinoma (OR = 3.41; 95% CI = 1.07-10.92), and suggestively positive, although not statistically significant, for serous (OR = 1.43; 95% CI = 0.82-2.49) and clear cell carcinoma (OR = 2.05; 95% CI = 0.36-11.57;
MeSH term(s)	Aged ; Biomarkers, Tumor/blood ; C-Reactive Protein/analysis ; Carcinogenesis ; Carcinoma/blood ; Carcinoma/classification ; Carcinoma/epidemiology ; Case-Control Studies ; Confidence Intervals ; Europe/epidemiology ; Female ; Follow-Up Studies ; Humans ; Inflammation ; Middle Aged ; Neoplasm Proteins/blood ; Odds Ratio ; Ovarian Neoplasms/blood ; Ovarian Neoplasms/epidemiology ; Prospective Studies ; Risk ; Risk Factors ; Sensitivity and Specificity ; United States/epidemiology
Chemical Substances	Biomarkers, Tumor ; Neoplasm Proteins ; C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2019-08-28
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-19-1554
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Article ; Online: Induction of cross-neutralizing antibodies by a permuted hepatitis C virus glycoprotein nanoparticle vaccine candidate

Nature Communications, Vol 13, Iss 1, Pp 1-

2022 Volume 16

Abstract: E1E2 spike on the hepatitis C virion is an important target for vaccine design. Here, the authors ...

Abstract	E1E2 spike on the hepatitis C virion is an important target for vaccine design. Here, the authors permute the subunits to generate E2E1 immunogens and show that mosaic nanoparticles displaying different E2E1 antigens elicit cross-neutralizing antibodies in rabbits.
Keywords	Science ; Q
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
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Article ; Online: Validation of the AUDIT and AUDIT-C for Hazardous Drinking in Community-Dwelling Older Adults

Yannic van Gils / Erik Franck / Eva Dierckx / Sebastiaan P. J. van Alphen / John B. Saunders / Geert Dom

International Journal of Environmental Research and Public Health, Vol 18, Iss 9266, p

2021 Volume 9266

Abstract: ... Disorders Identification Test (AUDIT) and its abbreviated form, the AUDIT-C. The aim of the present study is ... defined as drinking >10 units/week. Receiver operating characteristics (ROC) curves of AUDIT and AUDIT-C ... respectively of 80.7% and 81.3% and in women 100% and 71.7%, respectively. We found the AUDIT-C to perform well ...

Abstract	Background: One of the best-known tools in screening for hazardous drinking is the Alcohol Use Disorders Identification Test (AUDIT) and its abbreviated form, the AUDIT-C. The aim of the present study is to determine the cut-offs of both instruments in identifying hazardous drinking in older adults. Method: A sample of 1577 older adults completed a questionnaire regarding alcohol behavior. Hazardous drinking was defined as drinking >10 units/week. Receiver operating characteristics (ROC) curves of AUDIT and AUDIT-C were calculated and cut-off scores were derived. Results: Respectively 27.3% and 12.3% of older men and women drank >10 units/week. For the AUDIT the best trade-off between sensitivity and specificity was using a cut-off of ≥5 for men and ≥4 for women, which yielded in men sensitivity and specificity values respectively of 80.7% and 81.3% and in women 100% and 71.7%, respectively. We found the AUDIT-C to perform well with an optimal cut-off of ≥5 for men and ≥4 for women, which generated in men sensitivity and specificity values respectively of 76.5% and 85.3% and in women 100% and 74.1%, respectively. Conclusion: The AUDIT-C is accurate and sufficient in screening for hazardous drinking in community-dwelling older adults if the cut-offs are tailored by gender.
Keywords	older adults ; hazardous drinking ; AUDIT ; AUDIT-C ; validity ; Medicine ; R
Subject code	670
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Sequential and Simultaneous Immunization of Rabbits with HIV-1 Envelope Glycoprotein SOSIP.664 Trimers from Clades A, B and C.

Klasse, P J / LaBranche, Celia C / Ketas, Thomas J / Ozorowski, Gabriel / Cupo, Albert / Pugach, Pavel / Ringe, Rajesh P / Golabek, Michael / van Gils, Marit J / Guttman, Miklos / Lee, Kelly K / Wilson, Ian A / Butera, Salvatore T / Ward, Andrew B / Montefiori, David C / Sanders, Rogier W / Moore, John P

PLoS pathogens

2016 Volume 12, Issue 9, Page(s) e1005864

Abstract: ... specifically BG505 (clade A), B41 (clade B), CZA97 (clade C) and DU422 (clade C). The various trimers were ... B trimers, the clade C trimers also generated autologous Tier-2 NAb responses, the CZA97 trimers ... doing so more strongly and consistently than the DU422 trimers. The clade C trimers also cross-boosted ...

Abstract	We have investigated the immunogenicity in rabbits of native-like, soluble, recombinant SOSIP.664 trimers based on the env genes of four isolates of human immunodeficiency virus type 1 (HIV-1); specifically BG505 (clade A), B41 (clade B), CZA97 (clade C) and DU422 (clade C). The various trimers were delivered either simultaneously (as a mixture of clade A + B trimers) or sequentially over a 73-week period. Autologous, Tier-2 neutralizing antibody (NAb) responses were generated to the clade A and clade B trimers in the bivalent mixture. When delivered as boosting immunogens to rabbits immunized with the clade A and/or clade B trimers, the clade C trimers also generated autologous Tier-2 NAb responses, the CZA97 trimers doing so more strongly and consistently than the DU422 trimers. The clade C trimers also cross-boosted the pre-existing NAb responses to clade A and B trimers. We observed heterologous Tier-2 NAb responses albeit inconsistently, and with limited overall breath. However, cross-neutralization of the clade A BG505.T332N virus was consistently observed in rabbits immunized only with clade B trimers and then boosted with clade C trimers. The autologous NAbs induced by the BG505, B41 and CZA97 trimers predominantly recognized specific holes in the glycan shields of the cognate virus. The shared location of some of these holes may account for the observed cross-boosting effects and the heterologous neutralization of the BG505.T332N virus. These findings will guide the design of further experiments to determine whether and how multiple Env trimers can together induce more broadly neutralizing antibody responses.
MeSH term(s)	AIDS Vaccines/immunology ; Animals ; Antibodies, Neutralizing/immunology ; Female ; Glycoproteins/immunology ; HIV Antibodies/immunology ; HIV Infections/prevention & control ; HIV Infections/virology ; HIV-1/immunology ; Humans ; Immunization ; Protein Multimerization ; Rabbits ; Recombinant Proteins ; env Gene Products, Human Immunodeficiency Virus/genetics
Chemical Substances	AIDS Vaccines ; Antibodies, Neutralizing ; Glycoproteins ; HIV Antibodies ; Recombinant Proteins ; env Gene Products, Human Immunodeficiency Virus
Language	English
Publishing date	2016-09-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1005864
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Article ; Online: Plasma carotenoids, vitamin C, tocopherols, and retinol and the risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition cohort.

Bakker, Marije F / Peeters, Petra Hm / Klaasen, Veronique M / Bueno-de-Mesquita, H Bas / Jansen, Eugene Hjm / Ros, Martine M / Travier, Noémie / Olsen, Anja / Tjønneland, Anne / Overvad, Kim / Rinaldi, Sabina / Romieu, Isabelle / Brennan, Paul / Boutron-Ruault, Marie-Christine / Perquier, Florence / Cadeau, Claire / Boeing, Heiner / Aleksandrova, Krasimira / Kaaks, Rudolf /

Kühn, Tilman / Trichopoulou, Antonia / Lagiou, Pagona / Trichopoulos, Dimitrios / Vineis, Paolo / Krogh, Vittorio / Panico, Salvatore / Masala, Giovanna / Tumino, Rosario / Weiderpass, Elisabete / Skeie, Guri / Lund, Eiliv / Quirós, J Ramón / Ardanaz, Eva / Navarro, Carmen / Amiano, Pilar / Sánchez, María-José / Buckland, Genevieve / Ericson, Ulrika / Sonestedt, Emily / Johansson, Matthias / Sund, Malin / Travis, Ruth C / Key, Timothy J / Khaw, Kay-Tee / Wareham, Nick / Riboli, Elio / van Gils, Carla H

The American journal of clinical nutrition

2016 Volume 103, Issue 2, Page(s) 454–464

Abstract: Background: Carotenoids and vitamin C are thought to be associated with reduced cancer risk ... tocopherol, and vitamin C concentrations and risk of breast cancer.: Design ... zeaxanthin, β-cryptoxanthin, retinol, α-tocopherol, γ-tocopherol, and vitamin C. Breast cancer risk was ...

Abstract	Background: Carotenoids and vitamin C are thought to be associated with reduced cancer risk because of their antioxidative capacity. Objective: This study evaluated the associations of plasma carotenoid, retinol, tocopherol, and vitamin C concentrations and risk of breast cancer. Design: In a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort, 1502 female incident breast cancer cases were included, with an oversampling of premenopausal (n = 582) and estrogen receptor-negative (ER-) cases (n = 462). Controls (n = 1502) were individually matched to cases by using incidence density sampling. Prediagnostic samples were analyzed for α-carotene, β-carotene, lycopene, lutein, zeaxanthin, β-cryptoxanthin, retinol, α-tocopherol, γ-tocopherol, and vitamin C. Breast cancer risk was computed according to hormone receptor status and age at diagnosis (proxy for menopausal status) by using conditional logistic regression and was further stratified by smoking status, alcohol consumption, and body mass index (BMI). All statistical tests were 2-sided. Results: In quintile 5 compared with quintile 1, α-carotene (OR: 0.61; 95% CI: 0.39, 0.98) and β-carotene (OR: 0.41; 95% CI: 0.26, 0.65) were inversely associated with risk of ER- breast tumors. The other analytes were not statistically associated with ER- breast cancer. For estrogen receptor-positive (ER+) tumors, no statistically significant associations were found. The test for heterogeneity between ER- and ER+ tumors was statistically significant only for β-carotene (P-heterogeneity = 0.03). A higher risk of breast cancer was found for retinol in relation to ER-/progesterone receptor-negative tumors (OR: 2.37; 95% CI: 1.20, 4.67; P-heterogeneity with ER+/progesterone receptor positive = 0.06). We observed no statistically significant interaction between smoking, alcohol, or BMI and all investigated plasma analytes (based on tertile distribution). Conclusion: Our results indicate that higher concentrations of plasma β-carotene and α-carotene are associated with lower breast cancer risk of ER- tumors.
MeSH term(s)	Adult ; Antioxidants/analysis ; Antioxidants/therapeutic use ; Ascorbic Acid/blood ; Ascorbic Acid/therapeutic use ; Breast Neoplasms/epidemiology ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Breast Neoplasms/prevention & control ; Carotenoids/blood ; Carotenoids/therapeutic use ; Case-Control Studies ; Cohort Studies ; Diet ; Europe ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Proteins/metabolism ; Postmenopause ; Premenopause ; Prospective Studies ; Receptors, Estrogen/metabolism ; Risk ; Tocopherols/blood ; Tocopherols/therapeutic use ; Vitamin A/blood ; Vitamin A/therapeutic use ; beta Carotene/blood ; beta Carotene/therapeutic use
Chemical Substances	Antioxidants ; Neoplasm Proteins ; Receptors, Estrogen ; beta Carotene (01YAE03M7J) ; Vitamin A (11103-57-4) ; Carotenoids (36-88-4) ; alpha-carotene (45XWE1Z69V) ; Ascorbic Acid (PQ6CK8PD0R) ; Tocopherols (R0ZB2556P8)
Language	English
Publishing date	2016-01-20
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	280048-2
ISSN	1938-3207 ; 0002-9165
ISSN (online)	1938-3207
ISSN	0002-9165
DOI	10.3945/ajcn.114.101659
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