Sarcosine and other metabolites along the choline oxidation pathway in relation to prostate cancer—A large nested case–control study within the JANUS cohort in Norway

Abstract

Methyl group donors and intermediates of one-carbon metabolism affect DNA synthesis and DNA methylation, and may thereby affect prostate carcinogenesis. Choline, the precursor of betaine, and the one-carbon metabolite sarcosine have been associated with increased prostate cancer risk. Within JANUS, a prospective cohort in Norway (n 5 317,000) with baseline serum samples, we conducted a nested case-control study among 3,000 prostate cancer cases and 3,000 controls. Using conditional logistic regression, odds ratios (ORs) and 95% confidence intervals (CIs) for prostate cancer risk were estimated according to quintiles of circulating betaine, dimethylglycine (DMG), sarcosine, glycine and serine. High sarcosine and glycine concentrations were associated with reduced prostate cancer risk of borderline significance (sarcosine: highest vs. lowest quintile OR 5 0.86, CI 5 0.72-1.01, p trend 5 0.03; glycine: OR 5 0.83, CI 5 0.70-1.00, p trend 5 0.07). Serum betaine, DMG and serine were not associated with prostate cancer risk. However, individuals with a high glycine/serine ratio were at decreased prostate cancer risk (OR 5 0.74, CI 5 0.69-0.85, p trend < 0.001). This population-based study suggested that men with high serum sarcosine or glycine concentrations have modestly reduced prostate cancer risk. Ratios of metabolites reflecting one-carbon balance may be associated with prostate cancer risk, as demonstrated for the glycine/serine ratio, and should be explored in future studies.The folate-mediated one-carbon metabolism, which involves B-vitamins as enzymatic cofactors, is characterized by the transfer of methyl groups and may affect carcinogenesis by influencing methylation and synthesis of DNA.1 Betaine and its precursor choline may act as methyl group sources, 2 whereas intermediates involved in the transfer of one-carbon units may be hypothesized to reflect bioavailability of methyl groups.3 These factors may therefore affect the development and growth of cancer and should be investigated when studying the role of one-carbon metabolism in carcinogenesis. Interestingly, a high S-adenosylmethionine/S-adenosylhomocysteine ratio, which facilitates transmethylation reactions, has been associated with carcinogenesis. 4 Similarly, it may be hypothesized that ratios of one-carbon metabolites, which might reflect one-carbon balance, are related to carcinogenesis.Prostate cancer is the second most frequently diagnosed cancer among men globally. 5 Results from observational studies suggest that high concentrations of circulating folate or high vitamin B12 status are associated with increased prostate cancer risk, although reported associations were modest and sometimes inconsistent.6-8 Although increased prostate cancer risk was suggested in one trial among subjects receiving folic acid supplements, 9 recent meta-analyses did not suggest an association with increased prostate cancer risk. 10,11 Nevertheless, an observational population-based study previously showed

Sarcosine Is Uniquely Modulated by Aging and Dietary Restriction in Rodents and Humans

“…Elevated sarcosine levels in urine (Sreekumar et al, 2009) and serum (Koutros et al, 2013) have been associated with prostate cancer progression, although this relation has not been observed in other reports (de Vogel et al, 2014; Jentzmik et al, 2011). Elevated urine sarcosine levels were also associated with incident type 2 diabetes (Svingen et al., 2016), while low levels of sarcosine in blood have been linked with advanced arteriosclerosis (Hasokawa et al, 2012) and several neurological disorders, including neuropathic pain (Barthel et al, 2014), cerebral ischemia (Pinto et al, 2014), seizure (Socała et al, 2010), and Parkinson disease (Tsai et al, 2014).…”

Cloacal temperature responses of broiler chickens administered with betaine and ascorbic acid during the hot-dry season

“…Betaine is also very beneficial to osmotically stressed cells (Hoffmann et al 2013) and methyl group donors, such as betaine, influence DNA synthesis and methylation (de Vogel et al 2014). Methionine synthase and methylenetetrahydrofolate reductase play vital roles in the maintenance of correct DNA methylation levels because they are involved in the metabolism of the methyl group (Weiner et al 2014).…”

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.…”