Low fasting plasma concentration of the opioid precursor peptide pro-enkephalins has been linked to an increased risk of future breast cancer in middle-aged and postmenopausal women, according to a recent study published online ahead of print in the Journal of Clinical Oncology.

Researchers hypothesized that plasma levels of ENKs are predictive of long-term breast cancer risk. In experimental studies, ENKs and related opioids were implicated as negative regulators of breast cancer development through enhancing immune-mediated tumoral defense and by directly inhibiting cancer cells.

The study’s purposes were to measure pro-ENK, a surrogate for mature ENK, and assess its predictive value regarding development of breast cancer in a population of middle-aged women and in an independent study population.

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Pro-ENK was related in fasting plasma samples from 1,929 healthy women (mean age, 57.6 ± 5.9 years) of the Malmӧ Diet and Cancer study to breast cancer incidence (n = 123) during a median follow-up of 14.7 years. For replication, pro-ENK was related to risk of breast cancer (n = 130) in an older independent sample from the Malmӧ Preventive Project, which consisted of 1,569 women (mean age, 70.0 ± 4.4 years).

In the Malmӧ Diet and Cancer study, Pro-ENK was inversely related to the risk of breast cancer incidence. The results were replicated in the Malmӧ Preventive Project.