Abstract
Abstract Background: Although prostate cancer is the most commonly diagnosed malignancy and the second leading cause of cancer death in most developed populations, there are no well-established modifiable risk factors for the disease. Further, recent recommendations against routine prostate-specific antigen screening have cast doubt on its utility for early detection. Emerging metabolomic technologies that measure an array of low molecular weight biochemicals in blood and other tissue have the potential to identify compounds relevant to cancer etiology and early detection. Methods: We compared the metabolomic profiles of prospectively collected fasting serum from 74 prostate cancer cases and 74 controls selected from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of male smokers. Serum metabolomic profiling was conducted at Metabolon, Inc. (Durham, N.C.) using ultrahigh performance liquid chromatography/mass spectroscopy (LC-MS) and gas chromatography/mass spectroscopy (GC-MS); 420 identified compounds were available for analysis. We estimated the association between log-metabolite levels and prostate cancer by logistic regression. Multivariable models were adjusted for age, assay batch, trial supplement assignment, first-degree family history of prostate cancer, and physical activity. A threshold for statistical significance of 0.000119 was applied based on a Bonferroni correction for 420 tests. Results: Circulating 1-stearoylglycerol (1-SG, or 1-monostearin) was statistically significantly inversely associated with risk of prostate cancer after Bonferroni correction for multiple comparisons (OR=0.34, 95% CI=0.20 - 0.58, p=6.3 x 10-5). The magnitude of this association did not differ by disease aggressiveness and was observed for cases diagnosed up to 23 years after blood collection. Similar but somewhat weaker prostate cancer risk signals were also evident for glycerol and alpha-ketoglutarate. Conclusions: In this study of smokers, we found 1-SG to be inversely associated with risk of prostate cancer several years prior to diagnosis, supporting a role for dysregulation of lipid metabolism in prostate carcinogenesis. Further studies are needed to reexamine our findings, including particularly whether the 1-SG metabolite signal strength varies during a 10 or 20 year sub-clinical, prediagnostic period and may have potential utility as a prostate cancer early detection biomarker. Studies with serial blood sampling prior to diagnosis will be very informative in this regard. Whether the observed signal for 1-SG is independent of or correlated with PSA concentrations should also be examined. Citation Format: Alison M. Mondul, Steven Moore, Stephanie Weinstein, Satu Mannisto, Johsua Sampson, Demetrius Albanes. 1-stearoylglycerol is associated with risk of prostate cancer: Results from serum metabolomic profiling. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5068. doi:10.1158/1538-7445.AM2014-5068
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