From New Uses for Old Drugs to New Risks for Old Habits, AACR Prevention Research Meeting Presents Full Agenda

High-fiber diets, popular cures for old ailments, toothpaste additives, and a new turbo-charged aspirin were among several prime chemoprevention candidates discussed in cutting-edge research at the American Association for Cancer Research 3rd annual International Conference on Frontiers in Cancer Prevention Research. During the three-day meeting researchers had the opportunity to discuss early clinical research as well as basic research identifying new molecular targets for prevention. The following are some of the highlights. Apple Cider & Colon Cancer Prevention New research suggests that the admonition about trying to draw a single conclusion from a study of “apples and oranges,” may also be true for apples and apple cider. A study presented by Francis Raul, PhD, Research Director at the French National Institute for Health and Medical Research (INSERM), found a suggestion that apple cider—not apples—may be useful for prevention of colon cancer. Polyphenols, which are found in apples but are particularly abundant in apple cider, appear to trigger apoptosis in an animal model of colon cancer, he reported. The finding comes from an on-going INSERM investigation of natural antioxidants. He explained that polyphenols, specifically a type called procyanidins, are usually concentrated in the skin of the apple and the type of sweet apple used for cider has an especially high concentration—about 0.5 g of polyphenols per kilo. In cider, there are about 300 mg of procyanidins in each liter. “Drinking one glass of cider daily could provide significant protection,” he said. Moreover, the procyanidins in cider are not absorbed rapidly in the intestines, which enhances their efficacy. In a rat model of colon cancer the procyanidins, which work mainly on cell membranes, appear to alter the cell cycle in SW620 cancer cells and trigger apoptosis by activation of caspase 3, he said. Fruit & Vegetable Intake & NHL Prevention Once again there is evidence that a diet high in fresh fruits and vegetables can reduce the risk of cancer—but this time the benefit is not seen in a solid tumor cancer but rather in non-Hodgkin lymphoma (NHL). Linda E. Kelemen, RD, ScD, of Mayo Clinic School of Medicine, led a team of NCI-funded investigators who based their finding on a study of 450 patients with NHL and 400 matched, healthy controls. Dr. Kelemen reported that data collected from a dietary questionnaire suggest that men and women who eat three or more servings of vegetables—especially when that includes one serving of a green leafy vegetable and a half a serving of a cruciferous vegetable like broccoli or cauliflower—had a 40% lower risk of developing NHL than people who ate less than one serving of vegetables daily. Fresh fruit also appeared to be protective, but the reductions did not reach statistical significance. Interestingly, she said, higher intakes of selenium and zinc were also associated with a significantly (40% to 45%) lower risk of NHL, but there were no specific benefits linked to the antioxidant vitamins A, C, or E. Dr. Kelemen cautioned, however, that the study design is somewhat limiting because it relies on dietary recall of patients who already have cancer. Nonetheless, she said that the findings are consistent with a number of other studies in the literature. New ‘Super Aspirin’ May Be Potent Chemoprevention Agent An investigational turbo-charged aspirin called nitroaspirin (nitric oxide-donating aspirin) inhibited carcinogenesis in a mouse model of colon cancer. Basil Rigas, MD, PhD, Professor of Medicine and Chief of the Division of Cancer Prevention at State University of New York at Stony Brook, reported that nitroaspirin appears to slow or stop the proliferation of colon cancer cells. In the study, Min (multiple intestinal neoplasia) mice treated with two different positional isomers of nitroaspirin had significantly fewer tumors than mice treated with vehicle alone. “Nitroaspirin appears to be thousands of times more potent than traditional aspirin in inhibiting proliferation of these cancer cells,” Dr. Rigas said at a press conference. He said afterwards in an interview that human trials are expected to begin this month. The research is being funded by a $3.2 million grant from the National Cancer Institute. Old-Line Gout Drug May Find New Life in Chemoprevention Patients taking allopurinol, a drug long used to treat gout, for five or more years had about a two-thirds reduction in the relative risk of developing colon cancer, according to data presented by Gad Rennert, MD, PhD, Director of the CHS National Cancer Control Center and Technion Public Health Forum in Haifa, Israel. Allopurinol is a scavenger of reactive oxygen, he explained. It blocks xanthine oxidase, which produces a superoxide that promotes oxidative stress. While many studies have promoted the use of antioxidant vitamins to overcome oxidative stress, Dr. Rennert said, “this drug may be a better, more effective option.” The findings are based on data collected from 1,781 patients enrolled in the Molecular Epidemiology of Colorectal Cancer (MECC) Study between 1998 and 2004. Use of aspirin, NSAIDs, and family history were factored into the risk calculation. The use of the drug was measured by structured interviews matched to computerized prescription records. Since Israel has a national health care system, use of prescription records is considered an accurate measurement of compliance, he noted. At AACR's Annual Meeting this spring, this same group reported that hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (i.e., statins) are associated with reduced risk of colon cancer. Basil Rigas, MD, PhD, said that nitroaspirin appears to be thousands of times more potent than traditional aspirin in inhibiting proliferation of colon cancer cells in mice. Human trials are expected to start this month. Patients taking allopurinol for five or more years had a 67% reduction in the relative risk of developing colon cancer. Allopurinol is a scavenger of reactive oxygen, blocking xanthine oxidase, which produces a superoxide that promotes oxidative stress. Mexican-American Women Who Consume High-Fiber Diets Have Lower Levels of Circulating Estrogen Researchers at the Keck School of Medicine at the University of Southern California reported that Mexican-American women who increase their dietary fiber intake can reduce circulating estrogen—but that it is too soon to claim that lower estrogen levels translate into a reduced risk of breast cancer. Kristine Monroe, PhD, a postdoctoral fellow at Keck, analyzed data collected by the Multiethnic Cohort Study of Diet and Cancer, an ongoing study funded by the NIH. She and her colleagues compared information from dietary questionnaires and from biomarkers of dietary fiber intake found in blood samples and correlated that information with circulating estrogen levels in 252 Mexican-American women. The bottom line, said Dr. Monroe, was that “as fiber went up, estrogen went down.” Conversely, as dietary fat increased, so did circulating estrogen. Toothpaste Additive May Protect against Skin Cancer Sanguinarine, an additive often found in tooth paste, appears to reduce the cancer risk associated with ultraviolet-B (UVB) radiation, according to researchers from the University of Wisconsin. Nihal Ahmad, PhD, Assistant Professor in the Department of Dermatology, said that sanguinarine promotes production of proteins that induce apoptosis in UVB-damaged cells. Moreover, it also appears to serve as a barrier to the production of pro-proliferative proteins. When cells were treated with sanguinarine and then exposed to UVB radiation, there was an increase in Bax protein production and a decrease in Bcl-2 production, he reported. As a result there was an increase in apoptosis of 49% to 66%. Sanguinarine is an alkaloid found in the bloodroot plant. In herbal medicine it is widely touted for its antibacterial, antifungal, and anti-inflammatory properties. In toothpaste and mouthwash, sanguinarine offers protection against gingivitis. Diabetes Linked to Increased Risk of Pancreatic & Liver Caners Persons with diabetes have a three- to four-fold increased risk of liver cancer and are twice as likely to develop pancreatic cancer as are people without diabetes, according to research from the University of Montreal. Marie-Claude Rousseau, PhD, a postdoctoral fellow, reported findings from a case-control study of 3,288 men diagnosed with a dozen different types of cancer and 509 healthy controls. Diabetes was not associated with an increased risk of melanoma, non-Hodgkin lymphoma, cancers of the esophagus, stomach, colon, rectum, lung, prostate, bladder, or kidney. A diagnosis of diabetes was associated with a three-fold increase in the risk of liver cancer, and “people taking medications for diabetes have an even higher risk—almost four-fold higher than people who don't have diabetes,” Dr. Rousseau said. Hepatitis C Linked to NHL Hepatitis C virus (HCV), already the leading cause of hepatocellular carcinoma and the leading cause of the need for liver transplants, also significantly increases the risk of non-Hodgkin lymphoma, reported John Spinelli, PhD, Associate Professor of Health Care and Epidemiology at the University of British Columbia and a researcher with the British Columbia Cancer Agency. Nihal Ahmad, PhD, reported that sanguinarine promotes production of proteins that induce apoptosis in UVB-damaged cells and appears to serve as a barrier to the production of pro-proliferative proteins. Lab studies show an increase in apoptosis of 49% to 66%. HCV is associated with a six-fold increase in the risk of NHL, and HCV patients have a 17-fold higher risk for developing large B-cell lymphoma, he said. Dr. Spinelli and colleagues analyzed HCV prevalence in 550 NHL cases and 205 healthy controls. The data suggest that people exposed to HCV have a high risk for developing NHL, especially diffuse B-cell lymphoma, he said. This association, he noted, should be considered in the long-term management of HCV-infected patients. Betel Nuts Linked to Increase in Head & Neck Cancers in Taiwan In the musical South Pacific, betel nuts are memorialized by the line: “Bloody Mary's chewing, betel nuts. Bloody Mary's always chewing betel nuts…. Now ain't that too damn bad!” Fifty years later, cancer researchers confirm Rodgers and Hammerstein's prescience—chewing betel nuts is very bad (although the song appeared to be focused on what it did to the teeth). Chain Hsu, MD, PhD, of the department of oncology at the National Taiwan University Hospital in Taiwan, reports that men in Taiwan habitually chew betel quid, which is often rolled like a cigar and stuck in the cheek the way American ballplayers chew tobacco. Dr. Hsu said that in the period from 1981 to 2000 head and neck cancers increased by 85% among Taiwanese men.” That increase, he said, is linked to chewing betel quid. Betel quid is used as a stimulant, an appetite suppressor and a way to sweeten breath. For men born in the years 1972 to 1980, the relative risk for head and neck cancer is 45.67 compared with that for men born in the years 1932 to 1940, he said. The emergence of this high-risk cohort correlates with a 6.85-fold increase in the domestic production of betel quid, which suggests a strong correlation between betel quid and head and neck cancers, Dr. Hsu said.

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