Date

May 2009

Document Type

Thesis

Degree Name

M.S.

Institution

Oregon Health & Science University

Abstract

Background: Research suggests that inflammation may play a role in the development and progression of prostate cancer. Interleukin-6 (IL-6) and C-reactive protein (CRP) have been linked to prostate cancer progression and inflammatory cytokines have been correlated with an increased risk of prostate carcinogenesis. Omega-3 (n-3) fatty acids are known for their anti-inflammatory properties and have been linked to decreases in prostate cancer risk. Research indicates that levels of IL-6 and CRP decrease with higher n-3 fatty acid intakes. This study investigated the relationship between inflammation and outcome in men with and without prostate cancer as well as the modification of that relationship by n-3 fatty acids. Methods: This study was a secondary analysis of the data from a case-control study of diet and prostate cancer risk. IL-6 and CRP were measured in plasma of prostate cancer cases (n = 121) and biopsy negative controls (n = 240) collected at recruitment. Erythrocyte n-3 fatty acids (including eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA)) were analyzed using gas chromatographymass spectrometry. Prostate tissue inflammation was determined by immunohistochemistry (IHC). New incident cancer and cancer outcome was assessed using electronic patient medical records. Results: ALA was significantly higher in the subjects with low-grade cancer compared to biopsy negative controls, and subjects with high-grade cancer had significantly higher levels of IL-6 compared to the controls. Circulating levels of plasma IL-6 and CRP were associated with inflammation in the prostate in the biopsy negative controls. Controls were at the highest risk of having prostate tissue inflammation with IL-6 levels in the middle tertile (OR: 2.61, 95% CI: 1.37 – 4.97). IL-6 was significantly correlated with CRP in the biopsy negative controls and cancer cases (r = 0.471, 0.252, respectively, p <0.001 and 0.005, respectively). CRP was inversely correlated with DHA (r = -0.177, p < 0.001) and IL-6 was inversely correlated with EPA (r = -0.104, p = 0.48) in the cohort. When stratified by cancer status (biopsy negative controls and cancer cases), significant correlations between IL-6, CRP, and n-3 fatty acids were only observed in the biopsy negative controls. There was no significant association between IL-6, CRP, ALA, DHA, and EPA and the risk of prostate cancer. When the inflammatory markers and n-3 fatty acids were examined together, there was a significant increase in risk of prostate cancer in subjects with CRP levels in the middle category and lower ALA or higher DHA levels. Higher levels of EPA were associated with a significantly higher risk of developing prostate cancer, independently and with rising CRP levels. Conclusions: These results conflict with previous research showing a protective effect of DHA and EPA on prostate cancer risk, and an increased risk of cancer with higher levels of ALA. However, the subject population for this study had relatively low n-3 fatty acid levels compared to other cohorts. Research that is conducted in populations with adequate intakes of DHA and EPA or in conjunction with supplementation may provide a more accurate picture of their potential protective effects.

Identifier

doi:10.6083/M40C4SQ2

Division

Graduate Programs in Human Nutrition

School

School of Medicine

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.