Association of Sulfur Microbial Diet and the Risk of Lung Cancer in Women

Lung cancer is the leading cause of cancer death worldwide, and its burden among women-including women who have never smoked-continues to rise. The sulfur microbial diet (SMD), a dietary pattern linked to the abundance of sulfur-metabolizing gut bacteria that generate genotoxic hydrogen sulfide, has been associated with colorectal neoplasia, but whether it is associated with lung cancer risk in women is unknown.

We conducted a prospective cohort study of 114,981 women with valid 24-hour dietary assessments. An SMD score was derived from eight dietary components, and participants were classified into quartiles (Q1-Q4). Incident lung cancer was ascertained through cancer-registry linkage. Cox proportional-hazards models with sequential adjustment for sociodemographic, lifestyle, clinical and dietary factors estimated hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted cubic spline, subgroup, sensitivity, substitution and mediation analyses were also performed.

During follow-up, 802 incident lung cancer cases were documented. In the fully adjusted model, women in the highest SMD quartile had a higher risk of lung cancer than those in the lowest quartile (HR 1.25, 95% CI 1.02-1.54; P for trend = 0.036), and each 1-standard-deviation increase was associated with an 8% higher risk (HR 1.08, 95% CI 1.00-1.16). The dose-response association was positive and approximately linear, and the findings were robust across subgroup and sensitivity analyses. Substituting vegetables for processed meat was associated with a non-significantly lower risk (HR 0.93, 95% CI 0.86-1.01), and metabolic and inflammatory biomarkers showed minimal mediation.

Greater adherence to a more sulfur-microbial-promoting diet was associated with a modestly higher risk of incident lung cancer in women. These findings extend the relevance of the SMD beyond colorectal neoplasia and support dietary patterns favouring vegetables and legumes over processed meat for lung cancer prevention.