Dietary Phytoestrogens and Lung Cancer Risk

CONTEXT: Despite lung-specific in vitro and in vivo studies that support a chemopreventive role for phytoestrogens, there has been little epidemiologic research focused on dietary intake of phytoestrogens and risk of lung cancer. OBJECTIVE: To examine the relationship between dietary intake of phytoestrogens and risk of lung cancer. DESIGN, SETTING, AND PARTICIPANTS: Ongoing US case-control study of 1674 patients with lung cancer (cases) and 1735 matched healthy controls. From July 1995 through October 2003, participants were personally interviewed with epidemiologic and food frequency questionnaires to collect demographic information and to quantify dietary intake of 12 individual phytoestrogens. MAIN OUTCOME MEASURE: Risk of lung cancer, estimated using unconditional multivariable logistic regression analyses stratified by sex and smoking status and adjusted for established and putative lung cancer risk factors. RESULTS: Reductions in risk of lung cancer tended to increase with each increasing quartile of phytoestrogen intake. The highest quartiles of total phytosterols, isoflavones, lignans, and phytoestrogens were each associated with reductions in risk of lung cancer ranging from 21% for phytosterols (odds ratio OR, 0.79; 95% confidence interval CI, 0.64-0.97; P = .03 for trend) to 46% for total phytoestrogens from food sources only (OR, 0.54; 95% CI, 0.42-0.70; P<.001 for trend). Sex-specific effects were also apparent. For men, statistically significant trends for decreasing risk with increasing intake were noted for each phytoestrogen group, with protective effects for the highest quartile of intake ranging from 24% for phytosterols (OR, 0.76; 95% CI, 0.56-1.02; P = .04 for trend) to 44% for isoflavones (OR, 0.56; 95% CI, 0.41-0.76; P<.001 for trend), while in women, significant trends were only present for intake of total phytoestrogens from food sources only, with a 34% (OR, 0.66; 95% CI, 0.46-0.96; P = .01 for trend) protective effect for the highest quartile of intake. The apparent benefits of high phytoestrogen intake were evident in both never and current smokers but less apparent in former smokers. In women, statistically significant joint effects were evident between hormone therapy use and phytoestrogen intake. Specifically, high intake of the lignans enterolactone and enterodiol and use of hormone therapy were associated with a 50% (OR, 0.50; 95% CI, 0.31-0.68; P = .04 for interaction) reduction in risk of lung cancer. CONCLUSIONS: While there are limitations and concerns regarding case-control studies of diet and cancer, these data provide further support for the limited but growing epidemiologic evidence that phytoestrogens are associated with a decrease in risk of lung cancer. Confirmation of these findings is still required in large-scale, hypothesis-driven, prospective studies.