Abstract / Summary
The sulfur microbial diet (SMD) score is a microbiome-related dietary proxy derived from food groups associated with sulfur-metabolizing bacteria. Whether it is associated with lung cancer remains unclear. We analyzed 95,612 participants from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Cause-specific Cox regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer incidence and lung cancer-related mortality across SMD score quintiles and per 1-standard deviation increment. Restricted cubic splines and competing-risk methods were applied. We documented 1,561 incident lung cancers through 2009 and 2,109 lung cancer-related deaths through 2018; longer mortality ascertainment explains the larger death count. In the fully adjusted model, the highest versus lowest quintile was associated with higher lung cancer incidence (HR 1.23, 95% CI 1.03–1.47, P-trend = 0.023) and lung cancer-related mortality (HR 1.19, 95% CI 1.02–1.38, P-trend = 0.039). Continuous estimates were modest. Restricted cubic splines suggested positive associations approaching conventional statistical significance (P-overall = 0.072 and 0.065), without evidence of non-linearity. Associations were stronger for squamous and small cell carcinoma (P-heterogeneity = 0.011), and the pack-years interaction for mortality remained significant after false discovery rate correction ( p = 0.025). Fine-Gray estimates were attenuated. Higher SMD scores, particularly the highest versus lowest quintile, were associated with modestly higher lung cancer incidence and lung cancer-related mortality. Not applicable.