BMC Gastroenterology (Nov 2010)

Reduction of novel circulating long-chain fatty acids in colorectal cancer patients is independent of tumor burden and correlates with age

  • Tomonaga Takeshi,
  • Monden Morito,
  • Sekimoto Mitsugu,
  • Miyake Masakazu,
  • Takemasa Ichiro,
  • Elshoni Hoda,
  • Krenitsky Kevin,
  • Kavianpour Amir,
  • Grimmalt Bryan,
  • Yamazaki Yasuyo,
  • Heath Doug,
  • Ritchie Shawn A,
  • Matsubara Hisahiro,
  • Sogawa Kazuyuki,
  • Matsushita Kazuyuki,
  • Nomura Fumio,
  • Goodenowe Dayan B

DOI
https://doi.org/10.1186/1471-230X-10-140
Journal volume & issue
Vol. 10, no. 1
p. 140

Abstract

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Abstract Background Serum levels of novel hydroxy polyunsaturated ultra long-chain fatty acids (hPULCFAs) have been previously shown to be reduced in pre-treatment CRC patients compared to disease-free subjects, independent of disease stage. However, whether reduced levels of hPULCFAs result from the presence of cancer is currently unknown, as is the distribution of hPULCFAs in the general population. The following studies were carried out to assess whether conventional therapy would result in restoration of systemic hPULCFAs in CRC patients, and to investigate the relationship between hPULCFA levels and age. Methods Tandem mass spectrometry was used to determine serum levels of the 28 carbon-containing hPULCFA C28H46O4 (CRC-446) in the following cohorts: two independent Japanese CRC populations following surgical tumor removal (n = 86), a North American Caucasian CRC cohort (n = 150) following post-surgery combination chemo/radiation therapy, 990 randomly selected anonymized serum samples from subjects ranging between 11 and 99 years of age, as well as longitudinally collected serum samples from healthy normals (n = 8, up to 90 weeks) and stage IV CRC subjects on combination therapy (n = 12, up to 63 weeks). Results Serum CRC-446 levels in CRC subjects were significantly lower than controls (mean of 0.297 ± 0.07 ug/ml in controls versus 0.092 ± 0.03 in CRCs, p 0.05 between pre vs post surgery). CRC-446 levels showed a strong inverse association with age (p Conclusions Our findings show that CRC-446 levels are not affected by conventional CRC treatment and inversely correlate with age, which suggest that reduced serum CRC-446 levels likely exist prior to the development of CRC. Extrapolation of the results to a simple screening scenario showed that, compared to fecal blood testing, pre-colonoscopy screening using serum CRC-446 levels would require 80% fewer colonoscopies, would identify risk in subjects under the age of 50, and would result in increased numbers of early cases detected. The precise role these serum metabolites play in the aetiology of cancer development remains to be determined.