Plasma alkylresorcinol metabolites as biomarkers for whole-grain intake and their association with prostate cancer: a Swedish nested case-control study.

Background:Observational studies have mostly found no association between self-reported whole-grain (WG) intake and prostate cancer (PCa). Plasma alkylresorcinol metabolites have been suggested as biomarkers for WG intake in free-living populations. Methods:We investigated the major dietary and lifestyle determinants of plasma alkylresorcinol metabolites in a nested case-control study (1,016 cases and 1817 controls) in the Malmö Diet and Cancer Study. Multivariate adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were estimated to assess the association between plasma alkylresorcinol metabolites and PCa using logistic regression. Results:WG intake, waist circumference, educational level and smoking status were the main determinants of alkylresorcinol metabolites. We observed significant correlations between alkylresorcinol metabolites and WG (r=0.31) and fiber (r=0.27) intake. Metabolite concentration was positively associated with PCa risk (P overall effect = 0.0004) but the association was not linear (P = 0.04). The lowest risk was seen among men with moderate plasma concentrations. The OR for high compared to moderate plasma alkylresorcinol metabolites was 1.41 (95% CI: 1.10-1.80) for PCa. Conclusions:Results suggest that plasma alkylresorcinol metabolites are mainly determined by WG intake in this nested-case control study of Swedish men. The increased risk of PCa seen among men with high plasma alkylresorcinol metabolites requires further study, but residual confounding, detection bias or competing risk of non-PCa related deaths are plausible explanations that could not be ruled out. Impact:We found no evidence of a protective effect of WG on incident PCa. Further validation of alkylresorcinol metabolites as a biomarker for WG intake is needed.