Dietary phytoestrogens and lung cancer risk
Authors: Matthew B. Schabath, Ladia M. Hernandez, Xifeng Wu, Patricia C. Pillow, Margaret R. Spitz
Journal: Cancer Research (2005)

5800   Background: Dietary phytoestrogens (PE) are plant-derived compounds that possess estrogen-like activity. They have gained much attention for their chemopreventive role in cancers of the breast, colon, endometrium, and prostate. In spite of lung specific  in vitro  and  in vivo  studies that support a chemopreventive role for PE, there is limited epidemiologic research on PE intake and lung cancer. Methods: We compared self-reported dietary intake from food frequency questionnaires of 12 individual PE, which were also grouped according to PE food sources and categorized into summary measures of lignans, isoflavones, and total PE in 1,526 lung cancer cases and 1,483 matched healthy controls. Results: Cases compared to controls reported statistically significantly lower PE intake for 10 of the 12 individual PE. When total lignan intake was categorized by quartile, the highest quartile of lignan intake was associated with a 32% reduced risk of lung cancer (OR = 0.68; 95% CI 0.55 - 0.86), after adjusting for age, gender, ethnicity, smoking, and total energy intake. When the data were stratified by gender, the highest quartile of lignan intake was associated with a significantly protective effect for men (OR = 0.62) and borderline significant for women (OR = 0.82). But, when the lignans were categorized into PE food groups, the OR for the highest quartile of lignans derived from fruits and vegetables (enterolactone + enterodiol) was significantly protective both for men (OR = 0.59) and women (OR = 0.49). Because we have previously shown a protective effect for hormone replacement therapy (HRT), we examined joint effects of HRT with PE and noted that HRT use and high intake of enterolactone and enterodiol was associated with a 59% reduced risk and a 22% reduced risk for HRT use and low intake. In the highest quartile of isoflavone intake, there was a 33% overall reduced risk and reduced risks of 45% and 21% were evident for men and women, respectively. The OR for the highest quartile of soy-derived isoflavones (daidzein + genistein) was significantly protective both for men (OR = 0.28) and women (OR = 0.57). There was a 48% overall reduced risk in the fourth quartile of total PE intake with reduced risks of 46% and 39% both for men and women, respectively. Finally, we compared plasma levels of insulin-like growth factor I (IGF-I) (a putative risk factor for lung cancer) by PE intake and found that high intake of enterolactone and enterodiol was associated with statistically significantly lower IGF-I levels in women for both cases and controls compared to low intake. This pattern was also observed for men cases but not controls. Conclusions: These results suggest that high intake of dietary PE is associated with an overall decrease in lung cancer risk and that specific PE may be more beneficial for men while other PE, specifically enterolactone and enterodiol, may be more beneficial for women. That these PE were associated with lower IGF-1 levels may suggest a mechanistic basis for the protective effect.