Eating Foods With 'Weak Estrogens' May Help Reduce Lung Cancer Risk

In the Sept. 28 issue of the Journal of the American MedicalAssociation, the investigators report that study participants who atethe highest amount of foods with dietary "phytoestrogens" had a 46percent reduced risk of developing lung cancer, compared to those whoate the lowest quantity. More than 3,500 people participated in theresearch - making it the largest case-controlled study to examinedietary phytoestrogens and lung cancer risk in a U. S. population,according to the researchers.

The researchers also found gender specific benefits for differentclasses of phytoestrogens. Men who ate the highest amount ofsoy-isoflavins lowered their risk of developing lung cancer by 72percent, and women who ate the most fruit and vegetable by 41 percent.For those women who also used hormone replacement therapy, thisprotective effect was further enhanced.

"What we have found is intriguing and supports a small but growing bodyof evidence that suggests estrogenic-like compounds in food may helpprotect against development of lung and other cancers," says thestudy's lead author, Matthew Schabath, Ph.D., a postdoctoral researcherin the Department of Epidemiology. "But these kinds of studies, whichrely 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 alicense to continue smoking while increasing consumption of vegetables,says the study's principal investigator, Margaret Spitz, M.D., chair ofthe Department of Epidemiology.

"The best cancer prevention advice continues to be to stop smoking, andit is clear that all of us can benefit from healthy eating andexercising," Spitz says. "Still, our results generally show that higherintake of these foods resulted in lower lung cancer risk, and that iscertainly a tantalizing preliminary finding."

One of the most intriguing findings, says Schabath, is that people whohad never smoked had a reduced chance of developing the disease if theyate large quantities of phytoestrogen-rich food. "About 15 percent oflung cancers occur in lifetime never smokers, and besides exposures tosecond-hand smoke, other risk factors for these cancers are yet to bedetermined."

The study builds on the group's 2004 finding that women who usedhormone replacement therapy - which restores estrogen to postmenopausalwomen - had a lower risk of developing lung cancer than women who didnot use these agents, given a similar history of cigarette use. Ifestrogen drugs could protect against lung cancer, the researcherswondered if the same is true of foods that have naturally occurring lowlevels of estrogens. Several epidemiological studies of phytoestrogenicfoods had suggested that might be the case for breast, endometrial andprostate cancers. The researchers further noted that lung cancer ratesare substantially lower in Asian populations that typically eat largeramounts of phytoestrogens than is consumed in America.

Between 1995 and 2003, the research team enrolled 1,674 patientstreated for lung cancer at M. D. Anderson, and 1,735 healthy "control"volunteers from private clinics in the Houston area. The participantswere asked detailed questions about their diet for the year prior totheir enrollment or to their cancer diagnosis, with the assumption thatwhat they ate that year reflected their general eating pattern over anumber of years, Schabath says.

The two groups were matched in terms of age, gender, ethnicity andsmoking status. The researchers then divided consumption into threecategories of foods that contain phytoestrogens: isoflavones (soybeansand soy products, chickpeas and red clover), lignans (rye grains,linseeds, carrots, spinach, broccoli and other vegetables), andcoumesterol (bean, peas, clover, spinach and sprouts). They also lookedat phytosterols, a fourth group of plant-derived steroidal compoundsthat are believed to have estrogenic properties. These includevegetable oils, margarines, spreads, grains and certain fruits andvegetables.

The researchers divided consumption of these foods into quartiles, fromhighest use to lowest use, as measured against all participants. (Usewas not calculated by precise quantities, like cups, and so guidelineson what constitutes the highest-lowest quartile consumption are notavailable.) They then compared the two groups, and among their findingswere:

• 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 helpprotect against lung cancer development because they latch on toestrogen receptors that are present in both normal and malignant lungtissue, and this binding could exert a role in the regulation orderegulation of cancer growth. But they cannot say why women, ingeneral, seemed to benefit less from eating high quantities of specificclasses of food with phytoestrogens - as men do - or why former smokersdid seemed to benefit less.

The investigators caution that much more research is needed to prove adefinitive chemoprevention effect. For example, for reasons theresearchers do not understand, even a high consumption ofphytoestrogens did not reduce lung cancer risk in those people studiedwho had smoked and then quit.

"These findings need to be confirmed in prospective studies. We arejust at the beginning of our work to explore the connection betweenthese nutrients and lung cancer risk. The challenges and opportunitiesare enormous since lung cancer is the number one cause of cancermortality in the United States," says Spitz.

The study was primarily funded by Public Health Service grants andsupport from the National Cancer Institute and by the Flight AttendantMedical Research Institute. Co-authors include: Ladia M. Hernandez,M.S.; Xifeng Wu, M.D., Ph.D.; and Patricia C. Pillow, M.S.