Phytoestrogens and lung cancer risk: a nested case-control study in never-smoking Chinese women

BACKGROUND Since several lines of evidence suggest that estrogens may be involved in lung carcinogenesis, it has been hypothesized that intake of phytoestrogens, similar in molecular structure to mammalian estrogens, may be associated with lung cancer development. OBJECTIVE To prospectively evaluate the association between phytoestrogen exposure and lung cancer risk in never-smoking females. DESIGN We conducted a nested case-control study within a population-based prospective cohort study of adult females. A total of 478 incident lung cancer cases and their individually matched controls were identified among never-smoking females after a mean follow-up of 15.6 years. Habitual intake of and internal exposure to phytoestrogens were assessed by repeated dietary surveys and urinary biomarkers, respectively. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer were estimated in conditional logistic regression models. RESULTS After adjustment for potential confounders, a moderate intake of dietary isoflavones was inversely associated with lung cancer risk in never-smoking females, with OR for the second quartile vs lowest quartile of intake being 0.52 (95% CI: 0.35, 0.76). Further increasing intake did not convey additional benefits, with ORs (95% CI) for the third and fourth quartiles being 0.53 (0.36, 0.78) and 0.47 (0.31, 0.72), respectively (P-overall < 0.001 and P-nonlinearity = 0.006). A similar association shape was seen when exposure to isoflavones was assessed by urinary biomarkers. ORs (95% CI) for the second, third and fourth quartiles vs lowest quartile of urinary isoflavone excretion were 0.57 (0.39, 0.83), 0.64 (0.44, 0.92) and 0.60 (0.41, 0.86), respectively. The inverse association plateaued beyond the second quartile, with P-overall = 0.04 and P-nonlinearity = 0.15. Urinary excretion of gut-microbiota-derived metabolites of lignans was not related to lung cancer risk. CONCLUSIONS The study suggests that moderately increasing intake of isoflavone-rich foods is associated with lower risk of lung cancer in never-smoking females.