Serum Phospholipid Fatty Acids and Prostate Cancer Risk
Serum Phospholipid Fatty Acids and Prostate Cancer Risk
Inflammation may be involved in prostate cancer development and progression. This study examined the associations between inflammation-related phospholipid fatty acids and the 7-year-period prevalence of prostate cancer in a nested case-control analysis of participants, aged 55–84 years, in the Prostate Cancer Prevention Trial during 1994–2003. Cases (n = 1,658) were frequency matched to controls (n = 1,803) on age, treatment, and prostate cancer family history. Phospholipid fatty acids were extracted from serum, and concentrations of ω-3, ω-6, and trans-fatty acids (TFAs) were expressed as proportions of the total. Logistic regression models estimated odds ratios and 95% confidence intervals of associations of fatty acids with prostate cancer by grade. No fatty acids were associated with low-grade prostate cancer risk. Docosahexaenoic acid was positively associated with high-grade disease (quartile 4 vs. 1: odds ratio (OR) = 2.50, 95% confidence interval (CI): 1.34, 4.65); TFA 18:1 and TFA 18:2 were linearly and inversely associated with risk of high-grade prostate cancer (quartile 4 vs. 1: TFA 18:1, OR = 0.55, 95% CI: 0.30, 0.98; TFA 18:2, OR = 0.48, 95% CI: 0.27, 0.84). The study findings are contrary to those expected from the pro- and antiinflammatory effects of these fatty acids and suggest a greater complexity of effects of these nutrients with regard to prostate cancer risk.
Many lines of evidence support an important role for inflammation in the pathogenesis of prostate cancer. Proliferative inflammatory atrophy of the prostate may be the precursor lesion for prostate cancer, and both epidemiologic and animal experimental models report inverse associations between nonsteroidal antiinflammatory drugs and prostate cancer. Dietary compounds can also influence inflammation. Both in vitro and human studies have found ω-6 and trans-fatty acids (TFAs) to be proinflammatory and long-chain ω-3 fatty acids to be antiinflammatory. However, results from the few studies that have examined associations of these fatty acids in blood with prostate cancer risk have been inconsistent.
Here, we examine the associations of inflammation-related serum phospholipid fatty acids with prostate cancer risk in a case-control study nested within the Prostate Cancer Prevention Trial. We hypothesized that ω-6 and TFAs would be positively and ω-3 fatty acids inversely associated with risk. Several aspects of the Prostate Cancer Prevention Trial are unique: The presence or absence of prostate cancer was determined by biopsy, and cancer grade was determined by centralized, uniform pathology. Thus, although almost all prostate cancer cases were diagnosed as local stage, detection bias was minimized, and pathologic grading of cases was rigorous. Results from this study can help to inform whether these fatty acids should be further investigated for prostate cancer prevention.
Abstract and Introduction
Abstract
Inflammation may be involved in prostate cancer development and progression. This study examined the associations between inflammation-related phospholipid fatty acids and the 7-year-period prevalence of prostate cancer in a nested case-control analysis of participants, aged 55–84 years, in the Prostate Cancer Prevention Trial during 1994–2003. Cases (n = 1,658) were frequency matched to controls (n = 1,803) on age, treatment, and prostate cancer family history. Phospholipid fatty acids were extracted from serum, and concentrations of ω-3, ω-6, and trans-fatty acids (TFAs) were expressed as proportions of the total. Logistic regression models estimated odds ratios and 95% confidence intervals of associations of fatty acids with prostate cancer by grade. No fatty acids were associated with low-grade prostate cancer risk. Docosahexaenoic acid was positively associated with high-grade disease (quartile 4 vs. 1: odds ratio (OR) = 2.50, 95% confidence interval (CI): 1.34, 4.65); TFA 18:1 and TFA 18:2 were linearly and inversely associated with risk of high-grade prostate cancer (quartile 4 vs. 1: TFA 18:1, OR = 0.55, 95% CI: 0.30, 0.98; TFA 18:2, OR = 0.48, 95% CI: 0.27, 0.84). The study findings are contrary to those expected from the pro- and antiinflammatory effects of these fatty acids and suggest a greater complexity of effects of these nutrients with regard to prostate cancer risk.
Introduction
Many lines of evidence support an important role for inflammation in the pathogenesis of prostate cancer. Proliferative inflammatory atrophy of the prostate may be the precursor lesion for prostate cancer, and both epidemiologic and animal experimental models report inverse associations between nonsteroidal antiinflammatory drugs and prostate cancer. Dietary compounds can also influence inflammation. Both in vitro and human studies have found ω-6 and trans-fatty acids (TFAs) to be proinflammatory and long-chain ω-3 fatty acids to be antiinflammatory. However, results from the few studies that have examined associations of these fatty acids in blood with prostate cancer risk have been inconsistent.
Here, we examine the associations of inflammation-related serum phospholipid fatty acids with prostate cancer risk in a case-control study nested within the Prostate Cancer Prevention Trial. We hypothesized that ω-6 and TFAs would be positively and ω-3 fatty acids inversely associated with risk. Several aspects of the Prostate Cancer Prevention Trial are unique: The presence or absence of prostate cancer was determined by biopsy, and cancer grade was determined by centralized, uniform pathology. Thus, although almost all prostate cancer cases were diagnosed as local stage, detection bias was minimized, and pathologic grading of cases was rigorous. Results from this study can help to inform whether these fatty acids should be further investigated for prostate cancer prevention.
