Autoantibodies to MUC1 glycopeptides cannot be used as a screening assay for early detection of breast, ovarian, lung or pancreatic cancer

Brian Burford; Aleksandra Gentry-Maharaj; Ros Graham; Diane Allen; Johannes Pedersen; Ola Blixt; Evangelia-Ourania Fourkala; Deanna Bueti; Anne Dawnay; Jeremy Ford; Rakshit Desai; A Nedelman; Leonor David; Peter Trinder; Bruce Acres; Tilo Schwientek; Alex Gammerman; Celso Reis; Lara Silva; Hugo Osorio; Rachel Hallett; Hans Wandall; Ulla Mandel; Michael  Hollingsworth; Ian Jacobs; Ian Fentiman; Henrik  Clausen; Joyce Taylor-Papadimitriou; Usha Menon; Joy Burchell

doi:10.1038/bjc.2013.214

Autoantibodies to MUC1 glycopeptides cannot be used as a screening assay for early detection of breast, ovarian, lung or pancreatic cancer

Brian Burford, Aleksandra Gentry-Maharaj, Ros Graham, Diane Allen, Johannes Pedersen, Ola Blixt, Evangelia-Ourania Fourkala (Editor), Deanna Bueti, Anne Dawnay, Jeremy Ford, Rakshit Desai, A Nedelman, Leonor David, Peter Trinder, Bruce Acres, Tilo Schwientek, Alex Gammerman, Celso Reis, Lara Silva, Hugo OsorioRachel Hallett, Hans Wandall, Ulla Mandel, Michael Hollingsworth, Ian Jacobs, Ian Fentiman, Henrik Clausen, Joyce Taylor-Papadimitriou, Usha Menon, Joy Burchell

Comprehensive Cancer Centre

Research output: Contribution to journal › Article › peer-review

51 Citations (Scopus)

Abstract

Background: Autoantibodies have been detected in sera before diagnosis of cancer leading to interest in their potential as screening/early detection biomarkers. As we have found autoantibodies to MUC1 glycopeptides to be elevated in early-stage breast cancer patients, in this study we analysed these autoantibodies in large population cohorts of sera taken before cancer diagnosis.

Methods: Serum samples from women who subsequently developed breast cancer, and aged-matched controls, were identified from UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and Guernsey serum banks to formed discovery and validation sets. These were screened on a microarray platform of 60mer MUC1 glycopeptides and recombinant MUC1 containing 16 tandem repeats. Additional case–control sets comprised of women who subsequently developed ovarian, pancreatic and lung cancer were also screened on the arrays.

Results: In the discovery (273 cases, 273 controls) and the two validation sets (UKCTOCS 426 cases, 426 controls; Guernsey 303 cases and 606 controls), no differences were found in autoantibody reactivity to MUC1 tandem repeat peptide or glycoforms between cases and controls. Furthermore, no differences were observed between ovarian, pancreatic and lung cancer cases and controls.

Conclusion: This robust, validated study shows autoantibodies to MUC1 peptide or glycopeptides cannot be used for breast, ovarian, lung or pancreatic cancer screening. This has significant implications for research on the use of MUC1 in cancer detection.

Original language	English
Pages (from-to)	2045-2055
Number of pages	11
Journal	BJC: British Journal of Cancer
Volume	108
Issue number	10
DOIs	https://doi.org/10.1038/bjc.2013.214
Publication status	Published - 28 May 2013

Keywords

Autoantibodies
MUC1
Tumour associated glycoforms
Breast cancer
Early detection
Microarrays

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/bjc.2013.214

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Burford, B., Gentry-Maharaj, A., Graham, R., Allen, D., Pedersen, J., Blixt, O., Fourkala, E.-O. (Ed.), Bueti, D., Dawnay, A., Ford, J., Desai, R., Nedelman, A., David, L., Trinder, P., Acres, B., Schwientek, T., Gammerman, A., Reis, C., Silva, L., ... Burchell, J. (2013). Autoantibodies to MUC1 glycopeptides cannot be used as a screening assay for early detection of breast, ovarian, lung or pancreatic cancer. BJC: British Journal of Cancer, 108(10), 2045-2055. https://doi.org/10.1038/bjc.2013.214

@article{92ef9e93c3cf424383267efac0ddfcde,

title = "Autoantibodies to MUC1 glycopeptides cannot be used as a screening assay for early detection of breast, ovarian, lung or pancreatic cancer",

abstract = "Background: Autoantibodies have been detected in sera before diagnosis of cancer leading to interest in their potential as screening/early detection biomarkers. As we have found autoantibodies to MUC1 glycopeptides to be elevated in early-stage breast cancer patients, in this study we analysed these autoantibodies in large population cohorts of sera taken before cancer diagnosis.Methods: Serum samples from women who subsequently developed breast cancer, and aged-matched controls, were identified from UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and Guernsey serum banks to formed discovery and validation sets. These were screened on a microarray platform of 60mer MUC1 glycopeptides and recombinant MUC1 containing 16 tandem repeats. Additional case–control sets comprised of women who subsequently developed ovarian, pancreatic and lung cancer were also screened on the arrays.Results: In the discovery (273 cases, 273 controls) and the two validation sets (UKCTOCS 426 cases, 426 controls; Guernsey 303 cases and 606 controls), no differences were found in autoantibody reactivity to MUC1 tandem repeat peptide or glycoforms between cases and controls. Furthermore, no differences were observed between ovarian, pancreatic and lung cancer cases and controls.Conclusion: This robust, validated study shows autoantibodies to MUC1 peptide or glycopeptides cannot be used for breast, ovarian, lung or pancreatic cancer screening. This has significant implications for research on the use of MUC1 in cancer detection.",

keywords = "Autoantibodies, MUC1, Tumour associated glycoforms, Breast cancer, Early detection, Microarrays",

author = "Brian Burford and Aleksandra Gentry-Maharaj and Ros Graham and Diane Allen and Johannes Pedersen and Ola Blixt and Evangelia-Ourania Fourkala and Deanna Bueti and Anne Dawnay and Jeremy Ford and Rakshit Desai and A Nedelman and Leonor David and Peter Trinder and Bruce Acres and Tilo Schwientek and Alex Gammerman and Celso Reis and Lara Silva and Hugo Osorio and Rachel Hallett and Hans Wandall and Ulla Mandel and Michael Hollingsworth and Ian Jacobs and Ian Fentiman and Henrik Clausen and Joyce Taylor-Papadimitriou and Usha Menon and Joy Burchell",

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doi = "10.1038/bjc.2013.214",

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Burford, B, Gentry-Maharaj, A, Graham, R , Allen, D, Pedersen, J, Blixt, O, Fourkala, E-O (ed.), Bueti, D, Dawnay, A, Ford, J, Desai, R, Nedelman, A, David, L, Trinder, P, Acres, B, Schwientek, T, Gammerman, A, Reis, C, Silva, L, Osorio, H, Hallett, R, Wandall, H, Mandel, U, Hollingsworth, M, Jacobs, I, Fentiman, I, Clausen, H, Taylor-Papadimitriou, J, Menon, U & Burchell, J 2013, 'Autoantibodies to MUC1 glycopeptides cannot be used as a screening assay for early detection of breast, ovarian, lung or pancreatic cancer', BJC: British Journal of Cancer, vol. 108, no. 10, pp. 2045-2055. https://doi.org/10.1038/bjc.2013.214

TY - JOUR

T1 - Autoantibodies to MUC1 glycopeptides cannot be used as a screening assay for early detection of breast, ovarian, lung or pancreatic cancer

AU - Burford, Brian

AU - Gentry-Maharaj, Aleksandra

AU - Graham, Ros

AU - Allen, Diane

AU - Pedersen, Johannes

AU - Blixt, Ola

AU - Bueti, Deanna

AU - Dawnay, Anne

AU - Ford, Jeremy

AU - Desai, Rakshit

AU - Nedelman, A

AU - David, Leonor

AU - Trinder, Peter

AU - Acres, Bruce

AU - Schwientek, Tilo

AU - Gammerman, Alex

AU - Reis, Celso

AU - Silva, Lara

AU - Osorio, Hugo

AU - Hallett, Rachel

AU - Wandall, Hans

AU - Mandel, Ulla

AU - Hollingsworth, Michael

AU - Jacobs, Ian

AU - Fentiman, Ian

AU - Clausen, Henrik

AU - Taylor-Papadimitriou, Joyce

AU - Menon, Usha

AU - Burchell, Joy

A2 - Fourkala, Evangelia-Ourania

PY - 2013/5/28

Y1 - 2013/5/28

N2 - Background: Autoantibodies have been detected in sera before diagnosis of cancer leading to interest in their potential as screening/early detection biomarkers. As we have found autoantibodies to MUC1 glycopeptides to be elevated in early-stage breast cancer patients, in this study we analysed these autoantibodies in large population cohorts of sera taken before cancer diagnosis.Methods: Serum samples from women who subsequently developed breast cancer, and aged-matched controls, were identified from UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and Guernsey serum banks to formed discovery and validation sets. These were screened on a microarray platform of 60mer MUC1 glycopeptides and recombinant MUC1 containing 16 tandem repeats. Additional case–control sets comprised of women who subsequently developed ovarian, pancreatic and lung cancer were also screened on the arrays.Results: In the discovery (273 cases, 273 controls) and the two validation sets (UKCTOCS 426 cases, 426 controls; Guernsey 303 cases and 606 controls), no differences were found in autoantibody reactivity to MUC1 tandem repeat peptide or glycoforms between cases and controls. Furthermore, no differences were observed between ovarian, pancreatic and lung cancer cases and controls.Conclusion: This robust, validated study shows autoantibodies to MUC1 peptide or glycopeptides cannot be used for breast, ovarian, lung or pancreatic cancer screening. This has significant implications for research on the use of MUC1 in cancer detection.

AB - Background: Autoantibodies have been detected in sera before diagnosis of cancer leading to interest in their potential as screening/early detection biomarkers. As we have found autoantibodies to MUC1 glycopeptides to be elevated in early-stage breast cancer patients, in this study we analysed these autoantibodies in large population cohorts of sera taken before cancer diagnosis.Methods: Serum samples from women who subsequently developed breast cancer, and aged-matched controls, were identified from UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and Guernsey serum banks to formed discovery and validation sets. These were screened on a microarray platform of 60mer MUC1 glycopeptides and recombinant MUC1 containing 16 tandem repeats. Additional case–control sets comprised of women who subsequently developed ovarian, pancreatic and lung cancer were also screened on the arrays.Results: In the discovery (273 cases, 273 controls) and the two validation sets (UKCTOCS 426 cases, 426 controls; Guernsey 303 cases and 606 controls), no differences were found in autoantibody reactivity to MUC1 tandem repeat peptide or glycoforms between cases and controls. Furthermore, no differences were observed between ovarian, pancreatic and lung cancer cases and controls.Conclusion: This robust, validated study shows autoantibodies to MUC1 peptide or glycopeptides cannot be used for breast, ovarian, lung or pancreatic cancer screening. This has significant implications for research on the use of MUC1 in cancer detection.

KW - Autoantibodies

KW - MUC1

KW - Tumour associated glycoforms

KW - Breast cancer

KW - Early detection

KW - Microarrays

U2 - 10.1038/bjc.2013.214

DO - 10.1038/bjc.2013.214

M3 - Article

SN - 0007-0920

VL - 108

SP - 2045

EP - 2055

JO - BJC: British Journal of Cancer

JF - BJC: British Journal of Cancer

IS - 10

ER -

Autoantibodies to MUC1 glycopeptides cannot be used as a screening assay for early detection of breast, ovarian, lung or pancreatic cancer

Abstract

Keywords

UN SDGs

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