Association between sulfur microbial diet and the risk of esophageal cancer: a prospective cohort study in 101,752 American adults

Abstract

Background: Sulfur microbial diet (SMD) is a dietary pattern closely related to the intestinal load of sulfur-metabolizing microbes in humans. Diet and microbes may play an important role in the carcinogenesis of esophagus. However, epidemiological studies on SMD and esophageal cancer (EC) risk are scarce. Here, we evaluated this association based on a large American cohort.

Methods: In the cohort of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a SMD score was calculated to evaluate participants' compliance of SMD pattern, with higher scores presenting greater adherence. Cox hazards regression model was used to explore the association between the SMD score and the incidence of EC, esophageal squamous cell carcinoma (ESCC), and esophageal adenocarcinoma (EA). Subgroup analyses were conducted to figure out potential modifiers interacting with SMD on EC. Sensitivity analyses were used to testify the robustness of our main result.

Results: Among 101,752 participants, 154 EC cases, consisted of 41 ESCC cases and 97 EA cases, were identified with mean follow-up of 8.9 years. In the fully adjusted model, the highest versus the lowest quartiles of the SMD score were found to be associated with an increased risk of EC and ESCC (EC: HR_{Q4 vs. Q1}: 1.64; 95% CI: 1.05, 2.56; P = 0.016 for trend; ESCC: HR_{Q4 vs. Q1}: 2.37; 95% CI: 1.02, 5.47; P = 0.031 for trend), while not significantly associated with increases risk of EA (HR_{Q4 vs. Q1}: 1.41; P = 0.144 for trend). The main result remained through a series of sensitivity analyses. Subgroup analyses showed a stronger association between SMD and EC in participants with no regular consumption of aspirin (HR_{Q4 vs. Q1}: 1.90; 95% CI: 1.04, 3.47) than in those using aspirin regularly (HR_{Q4 vs. Q1}: 1.37; 95% CI: 0.71, 2.66) (P = 0.008 for interaction).

Conclusion: Adherence to the SMD pattern may be associated with increased risks of EC and ESCC, particularly for EC in individuals who do not regularly consume aspirin.

Keywords: Cox hazards regression analysis; Esophageal cancer; PLCO cancer screening trial; Sulfur microbial diet; Sulfur-metabolizing microbes.

Fig. 1

The flow chart of identifying eligible subjects. PLCO: Prostate, Lung, Colorectal, and Ovarian; BQ: Baseline Questionnaire; DHQ: Diet History Questionnaire

Fig. 2

The timeline and follow-up scheme of our study

Fig. 3

Dose-response analysis on the association of sulfur microbial diet score with the risk of esophageal cancer. Hazard ratio was adjusted for age (years), sex (male, female), race (white and non-white), marital status (married or living as married, other), smoking status (never, current, former), pack-years of smoking, educational level (college below, college graduate, post graduate), physical activity levels (min/week), body mass index (kg/m²), aspirin use (yes, no), pickled vegetables/fruit intake (g/day), history of diabetes (yes, no), history of hypertension (yes, no), and energy intake from diet (kcal/day)