Prospective evaluation of serum sarcosine and risk of prostate cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

Abstract

Metabolomic profiling has identified, sarcosine, a derivative of the amino acid glycine, as an important metabolite involved in the etiology or natural history of prostate cancer. We examined the association between serum sarcosine levels and risk of prostate cancer in 1122 cases (813 non-aggressive and 309 aggressive) and 1112 controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Sarcosine was quantified using high-throughput liquid chromatography-mass spectrometry. A significantly increased risk of prostate cancer was observed with increasing levels of sarcosine (odds ratio [OR] for the highest quartile of exposure [Q4] versus the lowest quartile [Q1] = 1.30, 95% confidence interval [CI]: 1.02, 1.65; P-trend 0.03). When stratified by disease aggressiveness, we observed a stronger association for non-aggressive cases (OR for Q4 versus Q1 = 1.44, 95% CI: 1.11, 1.88; P-trend 0.006) but no association for aggressive prostate cancer (OR for Q4 versus Q1 = 1.03, 95% CI: 0.73, 1.47; P-trend 0.89). Although not statistically significant, temporal analyses showed a stronger association between sarcosine and prostate cancer for serum collected closer to diagnosis, suggesting that sarcosine may be an early biomarker of disease. Interestingly, the association between sarcosine and prostate cancer risk was stronger among men with diabetes (OR = 2.66, 95% CI: 1.04, 6.84) compared with those without reported diabetes (OR = 1.23, 95% CI: 0.95-1.59, P-interaction = 0.01). This study found that elevated levels of serum sarcosine are associated with an increased prostate cancer risk and evidence to suggest that sarcosine may be an early biomarker for this disease.

Prospective Associations of Systemic and Urinary Choline Metabolites with Incident Type 2 Diabetes

“…As opposed to the findings from a recent Swedish Mendelian randomization study (7 ), we did not observe significant associations between plasma dimethylglycine and incident T2D. Also, there was no overall relationship between serum sarcosine and incident T2D; however, lower serum sarcosine was observed among patients with established T2D both in the current study and in a survey among US men (25 ).…”

Translating Genetic Risk Factors for Prostate Cancer to the Clinic: 2013 and Beyond

“…However, high levels of sarcosine were associated with nonaggressive PrCa cases with an OR of 1.44. The association between sarcosine levels and PrCa diagnosis was stronger in men with diabetes and among smokers [110].…”

Preliminary Reference Values of Serum Sarcosine, Prostate Specific Antigens And Testosterone in Apparently Healthy Males in Sokoto, Nigeria.

“…Many studies led to interest in sarcosine as a prostate cancer biomarker but in many of such studies, results have been conflicting; some indicated higher risk associated with higher levels of sarcosine and others, a lower risk 9,10 . In order to definitively assess the potential of serum sarcosine for further study, we are reporting a preliminary data for its reference value in our locality.…”