ABSTRACT: Importance:Dietary fiber (the main source of prebiotics) and yogurt (a probiotic food) confer various health benefits via modulating the gut microbiota and metabolic pathways. However, their associations with lung cancer risk have not been well investigated. Objective:To evaluate the individual and joint associations of dietary fiber and yogurt consumption with lung cancer risk and to assess the potential effect modification of the associations by lifestyle and other dietary factors. Design, Setting, and Participants:This pooled analysis included 10 prospective cohorts involving 1?445?850 adults from studies that were conducted in the United States, Europe, and Asia. Data analyses were performed between November 2017 and February 2019. Using harmonized individual participant data, hazard ratios and 95% confidence intervals for lung cancer risk associated with dietary fiber and yogurt intakes were estimated for each cohort by Cox regression and pooled using random-effects meta-analysis. Participants who had a history of cancer at enrollment or developed any cancer, died, or were lost to follow-up within 2 years after enrollment were excluded. Exposures:Dietary fiber intake and yogurt consumption measured by validated instruments. Main Outcomes and Measures:Incident lung cancer, subclassified by histologic type (eg, adenocarcinoma, squamous cell carcinoma, and small cell carcinoma). Results:The analytic sample included 627?988 men, with a mean (SD) age of 57.9 (9.0) years, and 817?862 women, with a mean (SD) age of 54.8 (9.7) years. During a median follow-up of 8.6 years, 18?822 incident lung cancer cases were documented. Both fiber and yogurt intakes were inversely associated with lung cancer risk after adjustment for status and pack-years of smoking and other lung cancer risk factors: hazard ratio, 0.83 (95% CI, 0.76-0.91) for the highest vs lowest quintile of fiber intake; and hazard ratio, 0.81 (95% CI, 0.76-0.87) for high vs no yogurt consumption. The fiber or yogurt associations with lung cancer were significant in never smokers and were consistently observed across sex, race/ethnicity, and tumor histologic type. When considered jointly, high yogurt consumption with the highest quintile of fiber intake showed more than 30% reduced risk of lung cancer than nonyogurt consumption with the lowest quintile of fiber intake (hazard ratio, 0.67 [95% CI, 0.61-0.73] in total study populations; hazard ratio, 0.69 [95% CI, 0.54-0.89] in never smokers), suggesting potential synergism. Conclusions and Relevance:Dietary fiber and yogurt consumption was associated with reduced risk of lung cancer after adjusting for known risk factors and among never smokers. Our findings suggest a potential protective role of prebiotics and probiotics against lung carcinogenesis.
