Polyamines in the Diet Related to High-Risk Adenomas

Orlando, FL—Individuals with the highest intake of dietary polyamines—common in orange juice, corn, red meat, peas and nuts—had larger colorectal adenomas and more advanced adenomas on colonoscopy screening, according to research presented at the 2010 Gastrointestinal Cancers Symposium.

The study was a follow-up to an earlier phase III study by the same researchers that found a polyamine-inhibitory regimen of difluoromethylornithine (DFMO) plus the COX inhibitor sulindac reduced the incidence of metachronous colorectal cancer by 70% and advanced adenomas by 90%.

The current study, presented by Kavitha P. Raj, MD, of the University of California, Irvine, evaluated the role of dietary polyamines in the occurrence of sporadic adenomas, and their effects on treatment with DFMO plus sulindac in preventing adenoma recurrences.

Increased polyamine synthesis and inflammation have been associated with colon carcinogenesis in both preclinical models and humans. It is possible that by decreasing polyamines, one might slow the cancer process, Dr Raj said.

The study subjects had a history of at least one resected adenoma within the past year, but no history of invasive cancer or hereditary colon cancer syndromes. Patient data were obtained from the previous multicenter colon adenoma prevention trial, and a self-administered food frequency questionnaire was collected.

Polyamine values for individual foods were calculated and reported. Of the different polyamines, dietary putrescine was the major contributor. Total dietary polyamine content was derived by adding putrescine, spermine, and spermidine, and patients were categorized into a highest quartile (75-100%), and a lower quartile group that included all three lowest quartiles (0-12%, 25-50%, 50-75%).

Tissue polyamine content was also evaluated from rectal mucosal biopsy specimens and compared with the dietary intake.

Baseline information was available for 222 of the initial 375 study participants, and for 188 patients who completed the study.

P

P

P

At baseline, adenomas > 1 cm were found in 43.6% of subjects in the highest dietary polyamine group compared with 26.4% in the lowest quartile ( = 0.01); advanced adenomas were identified in 52.7% versus 35.9% ( = 0.03) and high-grade adenomas in 32.7% versus 20.4%, respectively (= 0.06), Dr Raj reported.

Tissue levels of spermine and spermidine were both significantly elevated in the higher dietary group, versus the lowest quartile.

“We found, in the baseline characteristics, that there was a strong association between dietary and tissue polyamine levels,” Dr Raj said, “and higher dietary polyamines were associated with larger and more advanced adenomas.”

P

Risk of recurrence was significantly reduced in patients in the lower quartile group, with an 81% reduction in risk that was highly significant ( < 0.0001). Patients with lower intakes also had an 89% reduction in adenomas > 1 cm, a 91% reduction in high-grade adenomas, and a 94% reduction in advanced adenomas (adjusted for aspirin intake). All were statistically significant and “striking,” Dr Raj said.

Finally, dietary polyamine intake was found to alter the risk reduction of recurrent adenoma formation by DFMO plus sulindac, Dr Raj said. “The benefit we observed with DFMO plus sulindac in the trial was seen only in the lower dietary polyamine group, and there was no clear benefit of this regimen in the higher dietary polyamine group.”