Remodeling of the Tumor Microenvironment Predicts Increased Risk of Cancer in Postmenopausal Women: The Prospective Epidemiologic Risk Factor (PERF I) Study

Cecilie Liv Bager, Nicholas Willumsen, Stephanie Nina Kehlet, Henrik B. Hansen, Anne-Christine Bay-Jensen, Diana Julie Leeming, Katrine Dragsbæk Møller, Jesper Neergaard, Claus Christiansen, Estrid Høgdall, Morten Asser Karsdal

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Abstract

Background: An altered tumor microenvironment is one of the earliest signs of cancer and an important driver of the disease. We have seen previously that biomarkers reflecting tumor microenvironment modifications, such as matrix metalloproteinase (MMP)-degraded type 1 collagen (C1M), MMP-degraded type IV collagen (C4M), and citrullinated and MMP-degraded vimentin (VICM), were higher in the serum of cancer patients than in healthy controls. However, it is not known if these biomarkers could predict an increased risk of cancer. The aim of this study was to investigate whether C1M, C4M, and VICM were elevated prior to diagnosis of solid cancers in a large prospective study.

Methods: Between 1999 and 2001, 5,855 postmenopausal Danish women ages 48 to 89 years enrolled in the Prospective Epidemiologic Risk Factor study. Baseline demographics and serum were collected at the time of registration. Follow up cancer diagnoses were obtained from the Danish Cancer Registry in 2014. Serum C1M, C4M, and VICM levels were measured by competitive ELISAs.

Results: A total of 881 women were diagnosed with solid cancers after baseline. C1M, C4M, and VICM levels were significantly elevated in women diagnosed less than 1 year after baseline. C1M and VICM, but not C4M, were independent predictors of increased risk of cancer.

Conclusion: C1M, C4M, and VICM are elevated prior to cancer diagnosis. C1M and VICM are both independent predictors of increased cancer risk.

Impact: C1M and VICM are predictors for increased risk of cancer. Cancer Epidemiol Biomarkers Prev; 25(9); 1348–55. ©2016 AACR.
Original languageEnglish
JournalCancer Epidemiology, Biomarkers & Prevention
Volume25
Issue number9
Pages (from-to)1348-1355
ISSN1055-9965
DOIs
Publication statusPublished - 2016

Cite this

Bager, Cecilie Liv ; Willumsen, Nicholas ; Kehlet, Stephanie Nina ; Hansen, Henrik B. ; Bay-Jensen, Anne-Christine ; Leeming, Diana Julie ; Møller, Katrine Dragsbæk ; Neergaard, Jesper ; Christiansen, Claus ; Høgdall, Estrid ; Karsdal, Morten Asser. / Remodeling of the Tumor Microenvironment Predicts Increased Risk of Cancer in Postmenopausal Women: The Prospective Epidemiologic Risk Factor (PERF I) Study. In: Cancer Epidemiology, Biomarkers & Prevention. 2016 ; Vol. 25, No. 9. pp. 1348-1355.
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title = "Remodeling of the Tumor Microenvironment Predicts Increased Risk of Cancer in Postmenopausal Women: The Prospective Epidemiologic Risk Factor (PERF I) Study",
abstract = "Background: An altered tumor microenvironment is one of the earliest signs of cancer and an important driver of the disease. We have seen previously that biomarkers reflecting tumor microenvironment modifications, such as matrix metalloproteinase (MMP)-degraded type 1 collagen (C1M), MMP-degraded type IV collagen (C4M), and citrullinated and MMP-degraded vimentin (VICM), were higher in the serum of cancer patients than in healthy controls. However, it is not known if these biomarkers could predict an increased risk of cancer. The aim of this study was to investigate whether C1M, C4M, and VICM were elevated prior to diagnosis of solid cancers in a large prospective study.Methods: Between 1999 and 2001, 5,855 postmenopausal Danish women ages 48 to 89 years enrolled in the Prospective Epidemiologic Risk Factor study. Baseline demographics and serum were collected at the time of registration. Follow up cancer diagnoses were obtained from the Danish Cancer Registry in 2014. Serum C1M, C4M, and VICM levels were measured by competitive ELISAs.Results: A total of 881 women were diagnosed with solid cancers after baseline. C1M, C4M, and VICM levels were significantly elevated in women diagnosed less than 1 year after baseline. C1M and VICM, but not C4M, were independent predictors of increased risk of cancer.Conclusion: C1M, C4M, and VICM are elevated prior to cancer diagnosis. C1M and VICM are both independent predictors of increased cancer risk.Impact: C1M and VICM are predictors for increased risk of cancer. Cancer Epidemiol Biomarkers Prev; 25(9); 1348–55. {\circledC}2016 AACR.",
author = "Bager, {Cecilie Liv} and Nicholas Willumsen and Kehlet, {Stephanie Nina} and Hansen, {Henrik B.} and Anne-Christine Bay-Jensen and Leeming, {Diana Julie} and M{\o}ller, {Katrine Dragsb{\ae}k} and Jesper Neergaard and Claus Christiansen and Estrid H{\o}gdall and Karsdal, {Morten Asser}",
year = "2016",
doi = "10.1158/1055-9965.EPI-16-0127",
language = "English",
volume = "25",
pages = "1348--1355",
journal = "Cancer Epidemiology, Biomarkers & Prevention",
issn = "1055-9965",
publisher = "American Association for Cancer Research (A A C R)",
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Bager, CL, Willumsen, N, Kehlet, SN, Hansen, HB, Bay-Jensen, A-C, Leeming, DJ, Møller, KD, Neergaard, J, Christiansen, C, Høgdall, E & Karsdal, MA 2016, 'Remodeling of the Tumor Microenvironment Predicts Increased Risk of Cancer in Postmenopausal Women: The Prospective Epidemiologic Risk Factor (PERF I) Study', Cancer Epidemiology, Biomarkers & Prevention, vol. 25, no. 9, pp. 1348-1355. https://doi.org/10.1158/1055-9965.EPI-16-0127

Remodeling of the Tumor Microenvironment Predicts Increased Risk of Cancer in Postmenopausal Women: The Prospective Epidemiologic Risk Factor (PERF I) Study. / Bager, Cecilie Liv; Willumsen, Nicholas; Kehlet, Stephanie Nina; Hansen, Henrik B.; Bay-Jensen, Anne-Christine; Leeming, Diana Julie; Møller, Katrine Dragsbæk; Neergaard, Jesper; Christiansen, Claus ; Høgdall, Estrid; Karsdal, Morten Asser.

In: Cancer Epidemiology, Biomarkers & Prevention, Vol. 25, No. 9, 2016, p. 1348-1355.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Remodeling of the Tumor Microenvironment Predicts Increased Risk of Cancer in Postmenopausal Women: The Prospective Epidemiologic Risk Factor (PERF I) Study

AU - Bager, Cecilie Liv

AU - Willumsen, Nicholas

AU - Kehlet, Stephanie Nina

AU - Hansen, Henrik B.

AU - Bay-Jensen, Anne-Christine

AU - Leeming, Diana Julie

AU - Møller, Katrine Dragsbæk

AU - Neergaard, Jesper

AU - Christiansen, Claus

AU - Høgdall, Estrid

AU - Karsdal, Morten Asser

PY - 2016

Y1 - 2016

N2 - Background: An altered tumor microenvironment is one of the earliest signs of cancer and an important driver of the disease. We have seen previously that biomarkers reflecting tumor microenvironment modifications, such as matrix metalloproteinase (MMP)-degraded type 1 collagen (C1M), MMP-degraded type IV collagen (C4M), and citrullinated and MMP-degraded vimentin (VICM), were higher in the serum of cancer patients than in healthy controls. However, it is not known if these biomarkers could predict an increased risk of cancer. The aim of this study was to investigate whether C1M, C4M, and VICM were elevated prior to diagnosis of solid cancers in a large prospective study.Methods: Between 1999 and 2001, 5,855 postmenopausal Danish women ages 48 to 89 years enrolled in the Prospective Epidemiologic Risk Factor study. Baseline demographics and serum were collected at the time of registration. Follow up cancer diagnoses were obtained from the Danish Cancer Registry in 2014. Serum C1M, C4M, and VICM levels were measured by competitive ELISAs.Results: A total of 881 women were diagnosed with solid cancers after baseline. C1M, C4M, and VICM levels were significantly elevated in women diagnosed less than 1 year after baseline. C1M and VICM, but not C4M, were independent predictors of increased risk of cancer.Conclusion: C1M, C4M, and VICM are elevated prior to cancer diagnosis. C1M and VICM are both independent predictors of increased cancer risk.Impact: C1M and VICM are predictors for increased risk of cancer. Cancer Epidemiol Biomarkers Prev; 25(9); 1348–55. ©2016 AACR.

AB - Background: An altered tumor microenvironment is one of the earliest signs of cancer and an important driver of the disease. We have seen previously that biomarkers reflecting tumor microenvironment modifications, such as matrix metalloproteinase (MMP)-degraded type 1 collagen (C1M), MMP-degraded type IV collagen (C4M), and citrullinated and MMP-degraded vimentin (VICM), were higher in the serum of cancer patients than in healthy controls. However, it is not known if these biomarkers could predict an increased risk of cancer. The aim of this study was to investigate whether C1M, C4M, and VICM were elevated prior to diagnosis of solid cancers in a large prospective study.Methods: Between 1999 and 2001, 5,855 postmenopausal Danish women ages 48 to 89 years enrolled in the Prospective Epidemiologic Risk Factor study. Baseline demographics and serum were collected at the time of registration. Follow up cancer diagnoses were obtained from the Danish Cancer Registry in 2014. Serum C1M, C4M, and VICM levels were measured by competitive ELISAs.Results: A total of 881 women were diagnosed with solid cancers after baseline. C1M, C4M, and VICM levels were significantly elevated in women diagnosed less than 1 year after baseline. C1M and VICM, but not C4M, were independent predictors of increased risk of cancer.Conclusion: C1M, C4M, and VICM are elevated prior to cancer diagnosis. C1M and VICM are both independent predictors of increased cancer risk.Impact: C1M and VICM are predictors for increased risk of cancer. Cancer Epidemiol Biomarkers Prev; 25(9); 1348–55. ©2016 AACR.

U2 - 10.1158/1055-9965.EPI-16-0127

DO - 10.1158/1055-9965.EPI-16-0127

M3 - Journal article

VL - 25

SP - 1348

EP - 1355

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

SN - 1055-9965

IS - 9

ER -