Pre-diagnostic serum levels of inflammation markers and risk of ovarian cancer in the prostate, lung, colorectal and ovarian cancer (PLCO) screening trial

Our plain-English summary of Pre-diagnostic serum levels of inflammation markers and risk of ovarian cancer in the prostate, lung, colorectal and ovarian cancer (PLCO) screening trial, by B. Trabert, L. Pinto, P. Hartge, et al (Gynecologic Oncology, 2014).

The study

• Authors: B. Trabert, L. Pinto, P. Hartge, T. Kemp, A. Black, M.E. Sherman, L.A. Brinton, R.M. Pfeiffer, M.S. Shiels, A.K. Chaturvedi, A. Hildesheim, N. Wentzensen
• Journal: Gynecologic Oncology
• Published: 2014;135(2):297-304
• Cited by: 84 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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 5years 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.

Published by Elsevier Inc.

In plain English

This study did not measure asbestos. The authors mention asbestos only as background, among exposures linked to ovarian cancer that might act through inflammation. In a nested case-control study within the screening arm of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, the authors measured 46 inflammation-related markers in serum stored before diagnosis. The samples came from 149 women later diagnosed with ovarian cancer and 149 matched controls. Women in the highest third of C-reactive protein (CRP) had an odds ratio of 2.04 (95% CI 1.06 to 3.93) compared with the lowest third. For tumor necrosis factor alpha (TNF-α) the figure was 2.21 (1.06 to 4.63). The interleukin-8 association, 1.86 (0.96 to 3.61), was not statistically significant. In samples taken at least five years before diagnosis (56 cases), CRP and TNF-α remained associated with higher risk. After correction for multiple comparisons, only CRP with serous ovarian cancer met the authors' threshold. The authors concluded that CRP and TNF-α are associated with increased future risk of ovarian cancer, and said the findings require replication.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: nested case-control study within the screening arm of the PLCO Cancer Screening Trial
• Who was studied: 149 women with first-primary ovarian cancer diagnosed two to fourteen years after blood collection, and 149 individually matched controls without oophorectomy. All came from the screening arm of the PLCO trial, which recruited about 78,216 women aged 55 to 74 from ten cities between 1993 and 2001, with follow-up through December 31, 2008. Participants were 92.6% non-Hispanic white.
• Exposure: Pre-diagnostic serum levels of 46 inflammation-related markers. Eleven had prior hypotheses: CRP, IL-1α, IL-1β, IL-2, IL-6, IL-8, IL-10, TNF-α, IFN-γ, G-CSF and GM-CSF. The other 35 were studied without a prior hypothesis. No asbestos exposure was measured; asbestos appears only in the background.
• Main results:
  • All 149 cases: CRP highest versus lowest third, OR 2.04 (95% CI 1.06 to 3.93), p-trend 0.03.
  • All cases: detectable versus undetectable IL-1α, OR 2.23 (95% CI 1.14 to 4.34). This was based on 34 exposed cases, and the authors said it should be interpreted with caution.
  • All cases: TNF-α highest versus lowest third, OR 2.21 (95% CI 1.06 to 4.63), p-trend 0.04.
  • All cases: IL-8 highest versus lowest third, OR 1.86 (95% CI 0.96 to 3.61), p-trend 0.05. This association was not statistically significant.
  • Serous ovarian cancer (83 cases): CRP highest versus lowest third, OR 3.96, p-trend 0.008. The confidence interval is printed as 1.14 to 11.14 in the text but 1.41 to 11.14 in Table 3. For IL-8 in serous cancer the OR was 3.05 (95% CI 1.09 to 8.51), p-trend 0.03.
  • Cases with blood collected at least five years before diagnosis (56 cases): CRP highest versus lowest third, OR 4.51 (95% CI 1.08 to 18.82), p-trend 0.03. TNF-α highest versus lowest third, OR 5.55 (95% CI 1.19 to 25.83), p-trend 0.04.
  • After correction for multiple comparisons, only the association between CRP and serous ovarian cancer had a false discovery rate below 0.10. The associations of CRP, IL-1α, TNF-α and IL-8 with ovarian cancer overall had q-values of 0.13.
• The authors' conclusion: The authors concluded that their investigation provides evidence that serum levels of CRP and TNF-α are associated with increased future risk of ovarian cancer, 5 or more years after blood collection. They said that increased inflammation may be etiologically important and that additional research is needed to confirm the findings.
• Limitations the authors state:
  • Because of the limited sample size, associations for all markers were imprecise, and power was limited for subtypes other than serous tumors.
  • The findings require replication because of the large number of markers evaluated.
  • Markers were measured at only one time point.
  • Circulating levels may not reflect levels at local sites of inflammation relevant to ovarian cancer.
  • The IL-1α result rests on only 34 exposed cases, and fewer than 20% of IL-1α values were above the detection limit.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Ovarian cancer.

Medical terms in this study, explained in our Lexicon: Inflammation, Ovarian Cancer, Talc, nested case-control study, Biomarker, Odds Ratio, confidence interval, Necrosis.

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