In the Sept. 28 issue of the Journal of the American Medical Association, the investigators report that study participants who ate the highest amount of foods with dietary "phytoestrogens" had a 46 percent reduced risk of developing lung cancer, compared to those who ate the lowest quantity. More than 3,500 people participated in the research - making it the largest case-controlled study to examine dietary phytoestrogens and lung cancer risk in a U. S. population, according to the researchers.
The researchers also found gender specific benefits for different classes of phytoestrogens. Men who ate the highest amount of soy-isoflavins lowered their risk of developing lung cancer by 72 percent, and women who ate the most fruit and vegetable by 41 percent. For those women who also used hormone replacement therapy, this protective effect was further enhanced.
"What we have found is intriguing and supports a small but growing body of evidence that suggests estrogenic-like compounds in food may help protect against development of lung and other cancers," says the study's lead author, Matthew Schabath, Ph.D., a postdoctoral researcher in the Department of Epidemiology. "But these kinds of studies, which rely on a person's recall of the food they have eaten months before, have known limitations, and require more investigation."
As promising as they are, the study results should not be seen as a license to continue smoking while increasing consumption of vegetables, says the study's principal investigator, Margaret Spitz, M.D., chair of the Department of Epidemiology.
"The best cancer prevention advice continues to be to stop smoking, and it is clear that all of us can benefit from healthy eating and exercising," Spitz says. "Still, our results generally show that higher intake of these foods resulted in lower lung cancer risk, and that is certainly a tantalizing preliminary finding."
One of the most intriguing findings, says Schabath, is that people who had never smoked had a reduced chance of developing the disease if they ate large quantities of phytoestrogen-rich food. "About 15 percent of lung cancers occur in lifetime never smokers, and besides exposures to second-hand smoke, other risk factors for these cancers are yet to be determined."
The study builds on the group's 2004 finding that women who used hormone replacement therapy - which restores estrogen to postmenopausal women - had a lower risk of developing lung cancer than women who did not use these agents, given a similar history of cigarette use. If estrogen drugs could protect against lung cancer, the researchers wondered if the same is true of foods that have naturally occurring low levels of estrogens. Several epidemiological studies of phytoestrogenic foods had suggested that might be the case for breast, endometrial and prostate cancers. The researchers further noted that lung cancer rates are substantially lower in Asian populations that typically eat larger amounts of phytoestrogens than is consumed in America.
Between 1995 and 2003, the research team enrolled 1,674 patients treated for lung cancer at M. D. Anderson, and 1,735 healthy "control" volunteers from private clinics in the Houston area. The participants were asked detailed questions about their diet for the year prior to their enrollment or to their cancer diagnosis, with the assumption that what they ate that year reflected their general eating pattern over a number of years, Schabath says.
The two groups were matched in terms of age, gender, ethnicity and smoking status. The researchers then divided consumption into three categories of foods that contain phytoestrogens: isoflavones (soybeans and soy products, chickpeas and red clover), lignans (rye grains, linseeds, carrots, spinach, broccoli and other vegetables), and coumesterol (bean, peas, clover, spinach and sprouts). They also looked at phytosterols, a fourth group of plant-derived steroidal compounds that are believed to have estrogenic properties. These include vegetable oils, margarines, spreads, grains and certain fruits and vegetables.
The researchers divided consumption of these foods into quartiles, from highest use to lowest use, as measured against all participants. (Use was not calculated by precise quantities, like cups, and so guidelines on what constitutes the highest-lowest quartile consumption are not available.) They then compared the two groups, and among their findings were:
- Overall, consumption of phytoestrogens was statistically significantly higher in controls than in cases.
- The overall reduction in lung cancer risk was 46 percent for the highest intake of all phytoestrogens from food.
- For men, statistically significant trends were noted for each class of phytoestrogen, when they were consumed at the highest levels. For example, isoflavones reduced lung cancer risk by 44 percent, and lingans reduced the risk by 27 percent.
- In women, only intake of total phytoestrogens from food sources was statistically significantly higher in controls than in cases. High consumption of these foods reduced risk by 34 percent, but no effect was seen when individual classes of phytoestrogens were evaluated.
The researchers suggest that phytoestrogens may help protect against lung cancer development because they latch on to estrogen receptors that are present in both normal and malignant lung tissue, and this binding could exert a role in the regulation or deregulation of cancer growth. But they cannot say why women, in general, seemed to benefit less from eating high quantities of specific classes of food with phytoestrogens - as men do - or why former smokers did seemed to benefit less.
The investigators caution that much more research is needed to prove a definitive chemoprevention effect. For example, for reasons the researchers do not understand, even a high consumption of phytoestrogens did not reduce lung cancer risk in those people studied who had smoked and then quit.
"These findings need to be confirmed in prospective studies. We are just at the beginning of our work to explore the connection between these nutrients and lung cancer risk. The challenges and opportunities are enormous since lung cancer is the number one cause of cancer mortality in the United States," says Spitz.
The study was primarily funded by Public Health Service grants and support from the National Cancer Institute and by the Flight Attendant Medical Research Institute. Co-authors include: Ladia M. Hernandez, M.S.; Xifeng Wu, M.D., Ph.D.; and Patricia C. Pillow, M.S.