Brasky · Journal of the National Cancer Institute 2013 · Nested case-cohort study · n=2227

Plasma phospholipid fatty acids and prostate cancer risk in the SELECT trial.

Cited 310 times in the scientific literature.

Level 3 - non-randomized controlled study

Prospective case-cohort study nested within a randomized trial cohort.

PubMed 23843441 · doi:10.1093/jnci/djt174 · record verified 2026-08-30

What was done

This case-cohort study examined the association between plasma phospholipid fatty acids and prostate cancer risk among participants in the Selenium and Vitamin E Cancer Prevention Trial (SELECT). The analysis evaluated 834 incident prostate cancer cases (including 156 high-grade cases) compared with a randomly selected subcohort of 1393 men frequency matched on age and race. Proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for prostate cancer risk across quartiles of plasma fatty acids.

What was found

Compared with the lowest quartile, men in the highest quartile of long-chain omega-3 polyunsaturated fatty acids (LCω-3PUFA) had significantly increased risks of total prostate cancer (HR = 1.43, 95% CI = 1.09 to 1.88), low-grade prostate cancer (HR = 1.44, 95% CI = 1.08 to 1.93), and high-grade prostate cancer (HR = 1.71, 95% CI = 1.00 to 2.94). Higher linoleic acid (omega-6) was associated with lower risk of low-grade cancer (HR = 0.75, 95% CI = 0.56 to 0.99) and total prostate cancer (HR = 0.77, 95% CI = 0.59 to 1.01), without a clear dose-response relationship.

Why it matters

These findings suggest that high circulating levels of long-chain omega-3 fatty acids are associated with increased risks of both low- and high-grade prostate cancer, highlighting potential risks associated with high omega-3 intake.

Limits

The study is observational and nested within a trial cohort, meaning it cannot establish causality. Single-point plasma phospholipid biomarker measurements may reflect short-term rather than long-term exposure, and dietary sources versus supplements could not be differentiated in this analysis.

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