Black Raspberries May Inhibit Progression to Esophageal Cancer

Lisa M. Cockrell

December 10, 2007

December 10, 2007 (Philadelphia, Pennsylvania) — Dried black raspberries significantly reduce markers of oxidative stress in patients with Barrett's esophagus, according to a study reported at the American Association for Cancer Research 6th Annual International Conference on Frontiers in Cancer Prevention Research. This pilot study, presented by Laura Kresty, PhD, assistant professor at Ohio State University, in Columbus, was highlighted at an AACR press conference on diet and cancer prevention.

Barrett's esophagus, a complication resulting from chronic gastroesophageal reflux disease (GERD), is a premalignant condition associated with a 30- to 40-fold increased risk for the development of esophageal adenocarcinoma. This is a particularly deadly malignancy, with a 5-year survival rate of 15%. Patients with Barrett's esophagus experience chronic injury insults to the esophagus, resulting in the generation of reactive oxygen species and oxidative stress responses in the tissue. This can lead to key changes in the lipids, proteins, and genes within these tissues, causing tumor progression. Dr. Kresty commented that patients with Barrett's esophagus could particularly benefit from targeted chemopreventive interventions, especially those that would lower oxidative stress.

Dr. Kresty stated that black raspberries were chosen for this dietary chemoprevention study for a number of reasons. First, several epidemiologic studies have suggested that black raspberries are protective against a number of cancers, including esophageal cancer. Second, black raspberries in particular are known to have high levels of several compounds with potential anticancer properties, including antioxidants, vitamins, minerals, fiber, and anthocyanins, the pigments responsible for the characteristic dark coloring of the fruit. Finally, black raspberries are among the most extensively studied fruits in preclinical animal-based studies. In particular, animal models of esophageal cancer have suggested that black raspberries can decrease markers of oxidative stress and DNA damage.

In this phase 2a trial, 20 patients (mean age, 58.9 years) diagnosed with Barrett's esophagus were administered either 32 or 45 g (for females or males, respectively) daily of freeze-dried black raspberries over the course of 6 months. Forty-five grams corresponds to approximately 2 cups of whole black raspberries, but the fruit was dried into a powder to obtain a more concentrated sample, allowing patients to mix it into drinking water. Biopsies and urine and blood samples were taken at baseline and at 26 weeks, with an additional set of urine and blood samples at 12 weeks.

Changes in 2 urinary markers of global oxidative stress, a measure of the total body's oxidative stress, were assessed after administration of the freeze-dried berries. Most important, 8-epiprostaglandin F (8-isoprostane) declined significantly after berry consumption (< .05), with dramatic individual level declines occurring in 58% of the study patients. A second urinary marker, 8-hydroxy-2'-deoxyguanosine (8-OHdG), did not decrease significantly, but all of the patients who showed a decrease in 8-OHdG levels also had decreased 8-isoprostane levels, showing some level of correlation.

Levels of Urinary Biomarker 8-Isoprostane of Oxidative Stress (mg/mL of Urine)

Baseline Week 12 Week 26
1.59 × 10–10 1.38 × 10–10 1.30 × 10–10



 

Immunostaining of GSTπ, a protein important in tissue detoxification, revealed increased expression in the Barrett's tissue of 37% of the patients. This is a particularly promising result, said Dr. Kresty, given the increased oxidative stress these patients experience in this tissue. "If we can increase a molecule that helps to detoxify, we're moving things in the right direction."

The freeze-dried black raspberries did not induce any changes in the rates of cell proliferation within the esophageal tissue. Dr. Kresty commented that the investigators are still analyzing the data to determine whether any changes occurred in NFκB expression, a protein that plays roles in both inflammatory and growth signaling pathways.

An average 3.9-lb weight gain occurred among the study participants, but Dr. Kresty noted that this was not unexpected when weight changes in the general population were considered. However, the investigators did not rule out a possible connection between the weight gain and berry consumption, which added approximately 200 calories to the patient's diet.

According to Dr. Kresty, this study supports a broader message in the nutrition community to increase both fruit and vegetable consumption. "Patients can really do something to modify key pathways in cancer," she said. Dr. William Nelson, MD, PhD, from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, in Baltimore, Maryland, who was not involved in the study, agreed. "Diet is one of the great modifiable risk factors for the propensity to develop cancer. It's not surprising that there might be things that you can encounter in the diet  . . . things that might be helpful and protective."

Dr. Kresty believes that these positive results pave the way for a randomized placebo-controlled phase 2b trial, which would include a larger study population and a longer duration of intervention.

Sixth Annual International Conference on Frontiers in Cancer Prevention Research: Abstract B34. Presented December 7, 2007.

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