Abstract

Abstract Purpose: Fatty acid metabolism, particularly de novo lipogenesis, may be an important determinant of prostate cancer progression and mortality. However, epidemiologic data regarding the role of circulating fatty acids, as biomarkers of fatty acid intake and metabolism, on prostate cancer progression and mortality is scarce. Methods: We conducted a prospective cohort study among 582 Physicans’ Health Study participants who provided a blood sample in 1982 and who were later diagnosed with prostate cancer, between 1982 and 2006. Blood samples were kept frozen until they were assayed. Men were followed from the date of prostate cancer diagnosis until death or the end of follow-up (March 31, 2009). Blood levels of major types of fatty acids were measured using gas chromatography and expressed as percentage of total fatty acids. Men were categorized according to quintiles of blood fatty acid levels. Proportional hazards regression was used to estimate the relative risk (RR) and 95% confidence interval (95% CI) of prostate cancer specific mortality in a given quintile of fatty acid level in relation to the lowest quintile. Results: During 7,414 person-years of follow-up, 94 men died of prostate cancer. The median time between diagnosis and prostate cancer death was 14 years. The median time between blood draw and prostate cancer diagnosis was 9.5 years. Blood levels of all the mono-unsaturated, n-6 polyunsaturated and n-3 polyunsaturated fatty acids examined were unrelated to prostate cancer mortality. However, compared to men in the lowest quintile, the RRs (95% CIs) of prostate cancer mortality for men in increasing quintiles of blood stearic acid (18:0) levels were 1.90 (0.81-4.50), 3.61 (1.55-8.42), 2.29 (0.96-5.43) and 4.96 (2.10-11.7) (P, trend <0.001) after adjusting for age at diagnosis, race, body mass index, smoking status, clinical stage and tumor grade at diagnosis, and time between blood draw and prostate cancer diagnosis. Blood levels of the remaining saturated fatty acids examined were unrelated to prostate cancer mortality. Conclusions: Pre-diagnostic blood levels of stearic acid, a saturated fatty acid, are positively related to prostate cancer mortality. Since blood stearic acid levels are usually unrelated to diet, these data suggest that differences in fatty acid metabolism might be responsible for this association. It remains to be determined whether this finding is due to between-person differences in the activity of de novo lipogenesis enzymes or other metabolic factors that result in higher blood levels of stearic acid. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 896.

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