Dietary Stilbenes May Mitigate Risk of Lung Cancer: Evidence from Two Prospective Cohort Studies in the UK and Japan

(1) Background: Polyphenols are believed to prevent the development of various diseases by counteracting inflammation and oxidative stress. However, polyphenols are difficult to quantify in foods and show substantial variability in intake and epidemiological evidence on their relationship with lung cancer remains limited. This study explored the association between dietary polyphenols and lung cancer in two prospective cohorts. (2) Methods: Data from the UK Biobank and the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC) Study were used. The Phenol-Explorer^® database was used to assess the total and subtypes of dietary polyphenols. Lung cancer cases were identified using The International Classification of Diseases, 10th revision. Cox proportional hazards models were employed to estimate the association by hazard ratios (HRs) and 95% confidence intervals (CIs) among overall participants and in stratified analysis by smoking status and sex, which were further meta-analyzed. The associations of polyphenol compounds and food sources with lung cancer were also examined. (3) Results: A total of 177,971 and 57,971 participants from the UK Biobank and the JACC Study, respectively, were included. Wines and fruits were identified as the primary dietary sources of stilbenes. Dietary stilbenes were associated with a lower risk of lung cancer in fully adjusted models for both UK Biobank (HR: 0.849, 95% CI: 0.723-0.996) and JACC Study (HR: 0.803, 95% CI: 0.648-0.996), as well as in the meta-analysis (HR: 0.832, 95% CI: 0.732-0.946). (4) Conclusions: Considering pharmacokinetic properties and biological plausibility, our findings suggest that stilbenes may serve as markers of polyphenol-rich foods lowering lung cancer risk. Further biomarker-based and interventional studies are warranted to clarify causality and elucidate the underlying mechanisms.