Pre-diagnostic serum levels of inflammation markers and risk of ovarian cancer in the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial

Britton Trabert, Ligia Pinto, Patricia Hartge, Troy Kemp, Amanda Black, Mark E. Sherman, Louise A. Brinton, Ruth M. Pfeiffer, Meredith S. Shiels, Anil K. Chaturvedi, Allan Hildesheim, Nicolas Wentzensen

Research output: Contribution to journalArticle

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Abstract

Objective Pro-inflammatory mechanisms may explain the increased ovarian cancer risk linked to more lifetime ovulations, endometriosis, and exposure to talc and asbestos, as well as decreased risk with non-steroidal anti-inflammatory drugs. Limited data are available to estimate ovarian cancer risk associated with levels of circulating inflammatory markers.

Methods We conducted a nested case-control study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Pre-diagnostic serum levels of 46 inflammation-related biomarkers (11 with a priori hypotheses; 35 agnostic) were measured in 149 incident ovarian cancer cases and 149 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression and adjusted for identified covariates.

Results Increased ovarian cancer risk was associated with elevated levels of C-reactive protein (CRP) [tertile (T)3 vs. T1: OR (95% CI) 2.04 (1.06-3.93), p-trend = 0.03], interleukin (IL)-1α [detectable vs. undetectable: 2.23 (1.14-4.34)] and tumor necrosis factor alpha (TNF-α) [T3 vs. T1: 2.21 (1.06-4.63), p-trend = 0.04]. Elevated IL-8 was non-significantly associated with risk [T3 vs. T1: 1.86 (0.96-3.61), p-trend = 0.05]. In analyses restricted to serous ovarian cancer (n = 83), the associations with CRP and IL-8 remained or strengthened [CRP T3 vs. T1: 3.96 (1.14-11.14), p-trend = 0.008; IL-8 T3 vs. T1: 3.05 (1.09-8.51), p-trend = 0.03]. Elevated levels of CRP and TNF-α remained positively associated with ovarian cancer risk in analysis restricted to specimens collected at least 5 years before diagnosis (n = 56).

Conclusion These results suggest that CRP, IL-1α, IL-8, and TNF-α are associated with increased risk of subsequently developing ovarian cancer.

Original languageEnglish (US)
Pages (from-to)297-304
Number of pages8
JournalGynecologic Oncology
Volume135
Issue number2
DOIs
StatePublished - Nov 1 2014

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Early Detection of Cancer
Ovarian Neoplasms
Colorectal Neoplasms
Lung Neoplasms
Prostatic Neoplasms
Inflammation
C-Reactive Protein
Serum
Interleukin-8
Tumor Necrosis Factor-alpha
Interleukin-1
Odds Ratio
Confidence Intervals
Talc
Asbestos
Endometriosis
Ovulation
Case-Control Studies
Anti-Inflammatory Agents
Biomarkers

Keywords

  • Circulating inflammation markers
  • Cytokines
  • Inflammation
  • Nested case-control study
  • Ovarian cancer
  • Pre-diagnostic

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

Pre-diagnostic serum levels of inflammation markers and risk of ovarian cancer in the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial. / Trabert, Britton; Pinto, Ligia; Hartge, Patricia; Kemp, Troy; Black, Amanda; Sherman, Mark E.; Brinton, Louise A.; Pfeiffer, Ruth M.; Shiels, Meredith S.; Chaturvedi, Anil K.; Hildesheim, Allan; Wentzensen, Nicolas.

In: Gynecologic Oncology, Vol. 135, No. 2, 01.11.2014, p. 297-304.

Research output: Contribution to journalArticle

Trabert, B, Pinto, L, Hartge, P, Kemp, T, Black, A, Sherman, ME, Brinton, LA, Pfeiffer, RM, Shiels, MS, Chaturvedi, AK, Hildesheim, A & Wentzensen, N 2014, 'Pre-diagnostic serum levels of inflammation markers and risk of ovarian cancer in the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial', Gynecologic Oncology, vol. 135, no. 2, pp. 297-304. https://doi.org/10.1016/j.ygyno.2014.08.025
Trabert, Britton ; Pinto, Ligia ; Hartge, Patricia ; Kemp, Troy ; Black, Amanda ; Sherman, Mark E. ; Brinton, Louise A. ; Pfeiffer, Ruth M. ; Shiels, Meredith S. ; Chaturvedi, Anil K. ; Hildesheim, Allan ; Wentzensen, Nicolas. / Pre-diagnostic serum levels of inflammation markers and risk of ovarian cancer in the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial. In: Gynecologic Oncology. 2014 ; Vol. 135, No. 2. pp. 297-304.
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abstract = "Objective Pro-inflammatory mechanisms may explain the increased ovarian cancer risk linked to more lifetime ovulations, endometriosis, and exposure to talc and asbestos, as well as decreased risk with non-steroidal anti-inflammatory drugs. Limited data are available to estimate ovarian cancer risk associated with levels of circulating inflammatory markers.Methods We conducted a nested case-control study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Pre-diagnostic serum levels of 46 inflammation-related biomarkers (11 with a priori hypotheses; 35 agnostic) were measured in 149 incident ovarian cancer cases and 149 matched controls. Odds ratios (ORs) and 95{\%} confidence intervals (CIs) were calculated using conditional logistic regression and adjusted for identified covariates.Results Increased ovarian cancer risk was associated with elevated levels of C-reactive protein (CRP) [tertile (T)3 vs. T1: OR (95{\%} CI) 2.04 (1.06-3.93), p-trend = 0.03], interleukin (IL)-1α [detectable vs. undetectable: 2.23 (1.14-4.34)] and tumor necrosis factor alpha (TNF-α) [T3 vs. T1: 2.21 (1.06-4.63), p-trend = 0.04]. Elevated IL-8 was non-significantly associated with risk [T3 vs. T1: 1.86 (0.96-3.61), p-trend = 0.05]. In analyses restricted to serous ovarian cancer (n = 83), the associations with CRP and IL-8 remained or strengthened [CRP T3 vs. T1: 3.96 (1.14-11.14), p-trend = 0.008; IL-8 T3 vs. T1: 3.05 (1.09-8.51), p-trend = 0.03]. Elevated levels of CRP and TNF-α remained positively associated with ovarian cancer risk in analysis restricted to specimens collected at least 5 years before diagnosis (n = 56).Conclusion These results suggest that CRP, IL-1α, IL-8, and TNF-α are associated with increased risk of subsequently developing ovarian cancer.",
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T1 - Pre-diagnostic serum levels of inflammation markers and risk of ovarian cancer in the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial

AU - Trabert, Britton

AU - Pinto, Ligia

AU - Hartge, Patricia

AU - Kemp, Troy

AU - Black, Amanda

AU - Sherman, Mark E.

AU - Brinton, Louise A.

AU - Pfeiffer, Ruth M.

AU - Shiels, Meredith S.

AU - Chaturvedi, Anil K.

AU - Hildesheim, Allan

AU - Wentzensen, Nicolas

PY - 2014/11/1

Y1 - 2014/11/1

N2 - Objective Pro-inflammatory mechanisms may explain the increased ovarian cancer risk linked to more lifetime ovulations, endometriosis, and exposure to talc and asbestos, as well as decreased risk with non-steroidal anti-inflammatory drugs. Limited data are available to estimate ovarian cancer risk associated with levels of circulating inflammatory markers.Methods We conducted a nested case-control study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Pre-diagnostic serum levels of 46 inflammation-related biomarkers (11 with a priori hypotheses; 35 agnostic) were measured in 149 incident ovarian cancer cases and 149 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression and adjusted for identified covariates.Results Increased ovarian cancer risk was associated with elevated levels of C-reactive protein (CRP) [tertile (T)3 vs. T1: OR (95% CI) 2.04 (1.06-3.93), p-trend = 0.03], interleukin (IL)-1α [detectable vs. undetectable: 2.23 (1.14-4.34)] and tumor necrosis factor alpha (TNF-α) [T3 vs. T1: 2.21 (1.06-4.63), p-trend = 0.04]. Elevated IL-8 was non-significantly associated with risk [T3 vs. T1: 1.86 (0.96-3.61), p-trend = 0.05]. In analyses restricted to serous ovarian cancer (n = 83), the associations with CRP and IL-8 remained or strengthened [CRP T3 vs. T1: 3.96 (1.14-11.14), p-trend = 0.008; IL-8 T3 vs. T1: 3.05 (1.09-8.51), p-trend = 0.03]. Elevated levels of CRP and TNF-α remained positively associated with ovarian cancer risk in analysis restricted to specimens collected at least 5 years before diagnosis (n = 56).Conclusion These results suggest that CRP, IL-1α, IL-8, and TNF-α are associated with increased risk of subsequently developing ovarian cancer.

AB - Objective Pro-inflammatory mechanisms may explain the increased ovarian cancer risk linked to more lifetime ovulations, endometriosis, and exposure to talc and asbestos, as well as decreased risk with non-steroidal anti-inflammatory drugs. Limited data are available to estimate ovarian cancer risk associated with levels of circulating inflammatory markers.Methods We conducted a nested case-control study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Pre-diagnostic serum levels of 46 inflammation-related biomarkers (11 with a priori hypotheses; 35 agnostic) were measured in 149 incident ovarian cancer cases and 149 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression and adjusted for identified covariates.Results Increased ovarian cancer risk was associated with elevated levels of C-reactive protein (CRP) [tertile (T)3 vs. T1: OR (95% CI) 2.04 (1.06-3.93), p-trend = 0.03], interleukin (IL)-1α [detectable vs. undetectable: 2.23 (1.14-4.34)] and tumor necrosis factor alpha (TNF-α) [T3 vs. T1: 2.21 (1.06-4.63), p-trend = 0.04]. Elevated IL-8 was non-significantly associated with risk [T3 vs. T1: 1.86 (0.96-3.61), p-trend = 0.05]. In analyses restricted to serous ovarian cancer (n = 83), the associations with CRP and IL-8 remained or strengthened [CRP T3 vs. T1: 3.96 (1.14-11.14), p-trend = 0.008; IL-8 T3 vs. T1: 3.05 (1.09-8.51), p-trend = 0.03]. Elevated levels of CRP and TNF-α remained positively associated with ovarian cancer risk in analysis restricted to specimens collected at least 5 years before diagnosis (n = 56).Conclusion These results suggest that CRP, IL-1α, IL-8, and TNF-α are associated with increased risk of subsequently developing ovarian cancer.

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KW - Cytokines

KW - Inflammation

KW - Nested case-control study

KW - Ovarian cancer

KW - Pre-diagnostic

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