We all know that eating fruits, vegetables and soy products provides essential nutrition for a healthy lifestyle, while obesity leads to the opposite.
Yet proving the effect of nutrition, or obesity, on cancer is an experimental challenge and a focus for scientists. According to emerging evidence being presented at the 2007 Annual Meeting of the American Association for Cancer Research, eating well might still be one of the more pleasurable ways to prevent cancer and promote good health.
A novel mechanism for the chemoprotection by 3,3-diindolylmethane (DIM) and genistein for breast and ovarian cancer: Abstract 4217
Eating such foods as broccoli and soy are believed to offer some protection against cancer, but how this occurs is not well-understood. Now, in laboratory experiments, researchers at the University of California, Los Angeles, have discovered a biological mechanism whereby two compounds in these foods might lower the invasive and metastatic potential of breast and ovarian cancer cells.
They found that diindolylmethane (DIM), a compound resulting from digestion of cruciferous vegetables, and genistein, a major isoflavone in soy, reduce production of two proteins whose chemotactic attraction to each other is necessary for the spread of breast and ovarian cancers.
When applying purified versions of DIM and genistein to motile cancer cells, the researchers could literally watch these cells come to a near halt. When either compound was applied, migration and invasion were substantially reduced.
"We think these compounds might slow or prevent the metastasis of breast and ovarian cancer, which would greatly increase the effectiveness of current treatments," said Erin Hsu, a graduate student in molecular toxicology. "But we need to test that notion in animals before we can be more definitive."
Both DIM and genistein are already being developed for use as a preventive and a chemotherapy treatment for breast cancer, although more extensive toxicological studies are necessary, the researchers say.
The researchers looked at the potential of DIM and genistein to interfere with the "CXCR4/CXCL12 axis," which is known to play a central role in the metastasis of breast cancer and is also thought to play a role in the development of ovarian cancer. Primary cancer cells express very high levels of the CXCR4 chemokine receptor on the surface of their cells, and the organs to which these cancers metastasize secrete high levels of the CXCL12 chemokine ligand. This attraction stimulates the invasive properties of cancer cells and acts like a homing device, drawing the cancer cells to the organs they metastasize to.
When breast and ovarian cancer cell lines are exposed to purified DIM or genistein, levels of CXCR4 and CXCL12 messenger RNAs and proteins decrease in a dose-dependent manner, compared to untreated cells, according to Hsu.
To assess whether the compounds had any effect on the metastatic potential of the cells, the researchers placed the cells in one end of a compartment and watched how they moved toward CXCL12 at the other end. "The cells degrade the extracellular matrix in the upper compartment in order to move toward CXCL12 in the lower compartment, a system that represents a cell culture model for invasiveness," she said.
But if the cells are treated with either DIM or genistein, movement toward CXCL12 is reduced by at least 80 percent compared to untreated cells, the researchers say.
Hsu says that this same chemotactic attraction is thought to play a role in the development of more than 23 different types of cancer, and, so far, they have found that messenger RNA expression of CXCR4 and CXCL12 is substantially reduced when melanoma and prostate cancer cells are treated with the two compounds.
"We have also tested other phytochemicals and seen similar effects, indicating that this mechanism may mediate protective effects of other vegetable products as well," Hsu said.
The amount of DIM and genistein used in this study is probably comparable to use of a high dose of supplements, and is likely not achievable through consumption of food alone, the researchers say.
Flavonols and pancreatic cancer risk: The Multiethnic Cohort Study: Abstract 856
A study of food consumption in 183,518 residents of California and Hawaii has found that a diet high in flavonols might help reduce pancreatic cancer risk, especially in smokers. These compounds are generally ubiquitous in plant-based foods, but are found in highest concentrations in onions, apples, berries, kale and broccoli.
People who ate the largest amounts of flavonols had a 23 percent reduced risk of developing pancreatic cancer compared to those who ate the least, according to a research team led by Laurence Kolonel, M.D., Ph.D., at the Cancer Research Center of Hawaii.
Smokers gained the most benefit. Those who ate the most flavonols reduced their risk of developing pancreatic cancer by 59 percent, compared to those who ate the least, says the study's lead author, Ute N'thlings, DrPH, who conducted the study as a postdoctoral fellow in Hawaii and is now a researcher at the German Institute of Human Nutrition Potsdam-Rehbruecke.
'the effect was largest in smokers, presumably because they are at increased pancreatic cancer risk already," said N'thlings. Smoking is the only established risk factor for pancreatic cancer, and "short of stopping tobacco use, it has been difficult to consistently show lifestyle factors that might help protect against this deadly cancer," she says.
As part of a larger research project known as The Multiethnic Cohort Study, Kolonel and N'thlings followed the participants for an average of eight years after they filled out a comprehensive food questionnaire.
Although N'thlings says the study has a large statistical power because of the large number of pancreatic cancer cases (529) that occurred in the study population, she says that this one study cannot firmly answer the question of whether flavonols can prevent development of pancreatic cancer. "Further epidemiological studies in other populations and geographic regions are needed to confirm our findings," she said.
The study also is the first to examine prospectively specific classes of flavonols and pancreatic cancer risk.
The researchers looked at consumption of three flavonols: quercetin, which is most abundant in onions and apples; kaempferol, found in spinach and some cabbages; and myricetin, found mostly in red onions and berries.
Of the three individual flavonols, kaempferol was associated with the largest risk reduction (22 percent) across all participants. When the researchers divided intake into quartiles, and then compared highest intake to lowest, all the three classes of flavonols were associated with a significant trend toward reduced pancreatic cancer risk in current smokers, but not in never or former smokers. The interaction with smoking status was statistically significant for total flavonols, quercetin and kaempferol.
The researchers say their study did not examine the biological mechanisms by which these flavonols could exert a protective effect against pancreatic cancer. "But anti-carcinogenic effects of flavonoids in general have been attributed to the ability of these constituents to inhibit cell cycle, cell proliferation and oxidative stress, and to induce detoxification enzymes and apoptosis," N'thlings said.
Polyp characteristics, diet, lifestyle factors and high-risk colorectal adenoma recurrence in the polyp prevention trial: Abstract 861
Experts agree that people who have had three or more potentially precancerous adenomatous polyps removed during a colonoscopy should be "rescoped" in three years to make sure the polyps do not recur. But now researchers at the National Cancer Institute (NCI) have identified other factors that independently raise the risk of recurrence.
Two of these risk factors - being over 65 years old, and male - cannot be modified, but the third 'obesity' can, say the researchers.
The results can further help physicians stratify patients at greatest need for follow-up colonoscopies, they say, and can also inform patients about their own risk.
"In a situation where there are not enough physicians, or where doctors have long waiting lists for those who are not first-timers to a colon cancer check-up, then this risk stratification may help physicians prioritize which patients should be seen first," said Adeyinka Laiyemo, M.D., a cancer prevention fellow at NCI.
For patients, Dr. Laiyemo says that "it is important to follow your doctor's recommendation based on the nature of polyp removed during colonoscopy, and maintain a healthy weight. However, men should also recognize that they may be at a higher risk for developing worrisome polyps, and so should women who are over 65 years of age."