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

Nutrition Journal volume 23, Article number: 139 (2024) Cite this article

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: HRQ4 vs. Q1: 1.64; 95% CI: 1.05, 2.56; P = 0.016 for trend; ESCC: HRQ4 vs. Q1: 2.37; 95% CI: 1.02, 5.47; P = 0.031 for trend), while not significantly associated with increases risk of EA (HRQ4 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 (HRQ4 vs. Q1: 1.90; 95% CI: 1.04, 3.47) than in those using aspirin regularly (HRQ4 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.

Peer Review reports

Introduction

Esophageal cancer (EC) is reported to be the 7th most common and 6th most lethal cancer in the world, contributing to 18,440 new cases and 16,170 cancer-related deaths in America in 2020 [1, 2]. Although the incidence of EC shows a downward trend, its 5-year survival rate (20%) is the second lowest, only after pancreatic cancer [3, 4]. Therefore, it is imperative to explore some strategies to prevent the onset and progression of EC. Esophagus serves as the entrance into the gastrointestinal tract, its malignant transformation has been proved to be related to dietary habits and specific food items [5,6,7]. Epidemiologic studies have reported high intake of fruits, vegetables, and dietary fiber were associated with a decreased risk of EC [8, 9]. In contract, a significantly higher risk of EC was linked with higher intake of red and processed meat and higher alcohol consumption [8,9,10]. Recently, Nguyen et al. constructed and derived a particular pattern of food intake closely associated with the enrichment of sulfur-metabolizing microbes in human gut, namely sulfur microbial diet (SMD) [11], which is characterized by higher intake of processed meat, liquor, and low-calorie drinks, and lower intake of beer, legumes, vegetables, fruit juice, and sweets/desserts [11]. Among them, processed meat, liquor, and low-calorie drinks were found to be positively associated with the enrichment of sulfur-metabolizing microbes, whereas the remaining five components showed an inverse association [11]. Indeed, sulfur-metabolizing microbes can produce a large amount of genotoxic hydrogen sulfide gas (H2S), which plays a vital role in tumor pathogenicity [12, 13]. Previous prospective studies have demonstrated that the SMD pattern could significantly increase the risk of digestive system neoplasms, such as colorectal cancer and early-onset colorectal adenoma [11, 14, 15]. However, the relationship between the SMD and the incidence of EC remains uncertain. Given the features of SMD and the existed links between EC and diet, we sought to examine whether SMD may influence risk of EC incidence in a US population.

Materials and methods

Study population

The sample population used in this study was derived from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, which was a large population-based randomized controlled study. This trial aimed to ascertain whether a few screening procedures, such as colonoscopy, chest X-ray, digital rectal examination, prostate-specific antigen (PSA), cancer antigen 125 (CA-125), etc., could reduce the risk of death from PLCO malignancies [16]. In this trial, subjects were selected to participate in between November 1993 and September 2001, finally, 154,887 participants aged between 55 and 74 years were registered [16]. The registered participants were then randomly divided into the control and screening groups. Participants in the control group received standard cares, whereas those in the screening group were subjected to above-mentioned specific screening tests. All participants were asked to answer questionnaires related to demographics, lifestyle, dietary habits, health behaviors, medication use, diagnoses of diseases, and other exposures of interest. The Supplemental Questionnaire (SQX), Baseline Questionnaire (BQ), and Diet History Questionnaire (DHQ) were some of the specific questionnaires that were used in this study.

Based on the objectives of our study, the following participants were excluded: (1) Participants who failed to submit the BQ (n = 4918); (2) Participants who submitted an invalid DHQ (n = 38,462) (Invalid DHQ refers to DHQs that missed the completion date, subjects were deceased before DHQ completion, containing 8 or more missing/multiple frequency responses on DHQ, and having extreme energy consumption on DHQ [participants within the first and last percentile by gender]); (3) Participants having a history of cancer (excluding the nonmelanoma skin cancer) before DHQ analysis entry (n = 9684); and (4) participants with outcome events (diagnoses of EC, death, loss of follow-up, and the end of follow-up) occurred before DHQ completion (n = 71). The whole baseline sample included 101,752 individuals (Fig. 1). Written informed permission was required from every participant. The National Cancer Institute approved the experimental procedures and protocols used in this study (Project ID: PLCO-1134).

Fig. 1
figure 1

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

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Assessment of sulfur microbial diet scores

The DHQ, a self-administered, 124-item food frequency questionnaire, was used to collect dietary data in this study. The DHQ was designed to assess the serving sizes and frequency of food consumed for the 12 months prior to registration, its validity and dependability have already been described [17]. Participants’ consumption of each food was calculated by multiplying the serving sizes and food frequency.

SMD scores were calculated to quantify the participants’ adherence to SMD following an established method [11]. The food component groups in SMD included liquor, processed meat, low-calorie drinks, beer, fruit juice, legumes, other vegetables (including corn, eggplant, mixed vegetables, mushrooms, celery, green pepper, and summer squash), and sweets/desserts. Each food group was ranked into quartiles and was given positive or negative scores. For example, in the case of liquor, processed meat, and low-calorie drinks, participants below the lowest quartile, received a score of 1, whereas those above the highest quartile of a food group received a score of 4. As for beer, fruit juice, legumes, other vegetables, and whole grains, the scoring pattern was reversed (Supplementary Table 1). The SMD score was computed by summing the scores of the above-mentioned 8 food groups, and the total score of every participant ranged from 8 to 32. Higher SMD scores reflected greater adherence to the SMD pattern.

Assessment of the covariates

In this study, we evaluated the individual and population level risks associated with 15 potentially modifiable risk factors. The self-reported BQ was used to gather information regarding the demographic and lifestyle characteristics, including sex, race, marital status, body mass index (BMI), educational level, smoking status, regular consumption of aspirin, history of diabetes, history of hypertension, pack-years of smoking, and family history of EC. The terms “white” and “non-white” were used to represent the race, the marital status was described as “married or living as married” and “other”, and the educational level of the participants were described as “college below”, “college graduate”, and “postgraduate”. BMI was computed by dividing the weight (kg) by height (m2). Other risk factors that were evaluated using the aforementioned DHQ included age at DHQ completion, energy consumption from the diet, intake of pickled vegetables and fruits. The SQX was used to collect data on physical activity levels, which were calculated as the weekly sum of self-reported minutes of moderate to vigorous activity.

Outcome ascertainment

To gather data regarding newly diagnosed EC cases, the date of diagnosis, and more detailed relative information, participants were emailed a self-reporting annual study update form. Researchers checked the participants’ medical records after obtaining the consent of them to validate the diagnosis. Family reports and death certificates were used as supplemental information to identify deaths. It should be noted that the diagnosis of EC (ICD-O-2 codes: C150-C15, C153-155, and C158-C159) was the primary outcome of this study. The diagnoses of esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EA) were the secondary endpoints (ICD-O-2 codes: ESCC: 8070, and 8071; EA: 8140, 8480, and 8481).

Statistical analysis

This study includes a few variates with missing data. For variables containing < 5% missing values, categorical covariates such as marital status, educational level, aspirin consumption, history of diabetes and hypertension, family history of EC, and smoking status were imputed by the modal value; while the continuous covariates namely BMI and pack-years of smoking were imputed by the median value. In our analysis, the “physical activity levels” variable with > 25% missing values was assumed to be missing at random and implement using the Multivariate Imputation by Chained Equations (MICE) approach [18], which is a robust method of data imputation. In this method, missing data were replaced by iteratively drawing from the fitted conditional distributions of partially observed variables, given the observed and imputed values of the remaining variables in the imputation model. In this study, 25 imputed datasets were created for physical activity. Considering the heterogeneity of the imputed results, we took the mean value of the 25 imputed results for physical activity and applied it as a covariate in the final analysis. Supplementary Tables 2 and Supplementary Table 3 presents additional details regarding the relevant data imputation.

To calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of the EC, ESCC and EA incidence related to SMD scores, the Cox proportional hazards regression models were utilized. The follow-up period spanned from the DHQ completion date to the date of EC diagnosis, death, loss of follow-up, or the completion of follow-up (December 31, 2009), whichever occurred first (Fig. 2). Person-years were calculated by summing up the follow-up time of each participant and were used as the time variable. For all analyses, the SMD scores were divided into quartiles, and the first quartile (Q1) was set as the reference group. To estimate the linear trends of the association, the median scores of SMD in every quartile was assigned to every participant in this quartile, and the scores were regarded as continuous variables to conduct Cox regression analyses and acquire the P-value for trend. To adjust for potential relevant confounders, two multivariate Cox proportional hazards regression models were used. Particularly, Model 1 adjusted for a variety of demographic variables, including sex, age, race, educational level, and marital status. Potential effect moderating covariates, such as BMI, regular consumption of aspirin, levels of physical activity, history of hypertension, history of diabetes, energy intake from diet, smoking status, pack-years of smoking, and consumption of pickled vegetables/fruit, were further adjusted in Model 2. The multivariable-adjusted HRs and 95% CIs associated with a 1-point increment in SMD score were also estimated. In this study, we employed a restricted cubic spline (RCS) model with three strategically placed knots at the 10th, 50th, and 90th percentiles to investigate the nonlinear association between the SMD score and the risk of EC and its subtypes after adjusting for confounders. The structure of the RCS model, with its first knot dictating linear behavior at the lower exposure range, internal knots allowing the model to introduce nonlinearity within these intervals, and the final knot ensuring linear behavior at the upper range, was designed to effectively captures the complexity of the dose-response relationship. The “second spline” coefficient, representing the spline function’s coefficient after the first knot, is key to identifying the nonlinearity between the variable and the response.

Fig. 2
figure 2

The timeline and follow-up scheme of our study

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Prespecified subgroup analyses were conducted to assess the probable effect of the interaction factors, such as sex (male or female), age (> 65 or ≤ 65 years), BMI (> 30 kg/m2 or ≤ 30 kg/m2), regular consumption of aspirin (yes or no), smoking status (never or current/former), history of diabetes (yes or no), history of hypertension (yes or no), dietary energy intake (> medium or ≤ medium), and physical activity levels (> medium or ≤ medium). We used the likelihood ratio test as a mean to obtain P value in assessing the effect of adding the interaction term into a multivariate linear mixed-effects model. To test the robustness of the findings, some sensitivity analyses were carried out as follows: (1) Firstly, the participants with family history of EC were excluded; (2) Secondly, the participants in the control group were excluded; (3) Thirdly, participants with extreme BMI (defined as top 1% and bottom 1%) were excluded; (4) Additionally, participants with unbelievable energy intake (> 4000 kcal/day or < 500 kcal/day) [19] was excluded; (5) Physical activity were excluded from covariates to help better rule out the impact of such high missingness; (6) Finally, cases observed within the first 1 years of follow-up were exclude to test the potential inverse causation.

Cox regression analyses for each of these SMD components in relation to the risk of EC were further conducted to ascertain the principal contributing components to this relationship.

All data were statistically analyzed using the R (ver. 4.2.1) software. A two-tailed P-value < 0.05 indicated the significance level.

Results

Participant characteristics

A total of 101,752 participants were included in our analysis, which consisted of 49,494 (48.64%) males and 52,258 (51.36%) females, with the average (standard deviation) age of 65.53 (5.73). The mean (standard deviation) SMD score of subjects was 20.14 (3.09). According to the SMD scores, subjects were divided into quartiles [Quartile 1 (SMD score ≤ 18), n = 30685; Quartile 2 (SMD score 19–20), n = 25085; Quartile 3 (SMD score 21–22), n = 23103; Quartile 4 (SMD score ≥ 23), n = 22879] (Table 1). The higher the SMD scores, the greater the adherence to SMD. In comparison to the participants included in Quartile 1, those included in Quartile 4 were more likely to be male, white, and current/former smokers. In addition, the participants in the highest quartile of SMD scores showed higher pack-years of smoking, higher BMI, no aspirin regularly consumption, lower physical activity levels, energy intake from diet, and pickled vegetables/fruit intake versus the lowest quartiles.

Table 1 Baseline characteristics of study population according to sulfur microbial diet score*
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SMD scores and the risk of esophageal cancer and its subtypes

During follow-up period (900,654 person years, median follow-up time 9.4 years), 154 incident EC events, consisted of 41 ESCC cases and 97 EA cases, occurred with an incidence rate of 1.7 per 10,000 person-years. In the unadjusted model, participants in the highest quartile had a significantly higher risk of EC than those in the lowest quartile (HRQ4 vs. Q1: 2.05; 95% CI: 1.33, 3.14; P < 0.001 for trend; HR per 1-point increment: 1.11; 95% CI: 1.05, 1.17; P < 0.001) (Table 2). After full adjustment for potential confounders, positive association of the SMD score with the risk of EC was also observed (HRQ4 vs. Q1: 1.64; 95% CI: 1.05, 2.56; P = 0.016 for trend; HR per 1-point increment: 1.08; 95% CI: 1.02, 1.14; P = 0.005) (Table 2). A similar positive relationship between SMD score and the risk of ESCC was documented (HRQ4 vs. Q1: 2.37; 95% CI: 1.02, 5.47; P = 0.031 for trend; HR per 1-point increment: 1.14; 95% CI: 1.03, 1.26; P = 0.014). However, in the Cox regression analysis for EA, we did not observe significant positive association (HRQ4 vs. Q1: 1.41; 95% CI: 0.81, 2.45; P = 0.144 for trend; HR per 1-point increment: 1.07; 95% CI: 1.00, 1.14; P = 0.062) (Table 2). The restricted cubic spline model indicated that SMD scores were positively related to EC and ESCC incidence in a linear dose-dependent manner (P > 0.05 for nonlinearity) (Fig. 3).

Table 2 Hazard ratios of the association of sulfur microbial diet scores with the risk of esophageal cancer and its subtypes
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Fig. 3
figure 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)

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Additional analyses

In subgroup analyses of age, sex, BMI, regular consumption of aspirin, smoking status, food energy intake from diet, history of hypertension, history of diabetes, and physical activity levels, the association between SMD score and EC risk was stronger in participants with no regular consumption of aspirin (HRQ4 vs. Q1: 1.90; 95% CI: 1.04, 3.47) than in those using aspirin regularly (HRQ4 vs. Q1: 1.37; 95% CI: 0.71, 2.66) (P = 0.008 for interaction) (Table 3). A high robustness of our primary result was obtained with a series of sensitive analyses (Table 4). The positive association between the SMD score and the EC incidence was still recorded when participants with a family history of EC, and in the control group were separately excluded. Additionally, after excluding participants with extreme BMI levels (defined as top 1% and bottom 1%) or extreme levels of energy intake (> 4000 kcal/day or < 500 kcal/day) [19], no significant alterations in the final results were observed (Table 4). Furthermore, when excluded physical activity from covariates, the positive association between SMD and EC still existed. Excluding cases observed within the first 1 years of follow-up, the main result remained (with a marginal P value = 0.052) (Table 4).

Table 3 Subgroup analyses on the association of SMD scores with the risk of esophageal cancer
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Table 4 Sensitivity analyses on the association of sulfur microbial diet scores with the risk of esophageal cancer a
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Individual components of SMD and the risk of esophageal cancer

According to Supplementary Table 4, for processed meat, liquor, low-calorie drinks, beer, fruit juice, legumes, other vegetables, and sweets/desserts, no significant associations were observed with the risk of EC.

Discussion

In the multicenter cohort of American adults from PLCO Cancer Screening Trail, we found that greater adherence to SMD pattern was associated with an increased risk of EC and ESCC. Interestingly, a significant stronger positive associate between SMD pattern and EC was found in participants without regular consumption of aspirin. The restricted cubic spline models showed that the relationships were linear and dose-dependent, and the finding was validated by multiple sensitivity analyses.

Researches on the relationship between dietary patterns and EC risk began as early as the 20th century. These included studies on the Dietary Inflammatory Index [20], Mediterranean Diet [21], and glycemic index and glycemic load diet [22]. It is worth noting that our study was the first to identify the positive association between SMD pattern and the risk of EC and ESCC. Previous studies have shown that adherence to SMD may lead to the enrichment of sulfur-metabolizing microbes, including Bacteroides, Acidaminococcus, Escherichia coli (E. coli), Parabacteroides, Streptococcus, and Veillonella sp., et al., in the human gut [14]. Dysbiosis of gut microbiota is possible response for the occurrence and development of EC. Several existing studies have provided insights into this relationship. Zaidi et al. figured out that E. coli primarily existed in Barrett’s esophagus and esophageal adenocarcinoma in their analysis of 54 samples [23]. Another study of Narikiyo M et al. suggested the adverse effects of Streptococcus on EC and the eradication of Streptococcus can reduce the risk of EC recurrence [24]. In addition, Bacteroidetes were also proved to significantly increase in EC samples [25, 26]. H2S, as one of the major metabolic products of sulfur-metabolizing microbes, has been found to be associated with tumor formation. Some studies have indicated that excessive production of H2S is linked to the development of tumors [27, 28], and the production of H2S increased in many cancers including colorectal cancer, gastric cancer, etc [29]. However, there is no consensus on the association between H2S and EC.

Several mechanisms could be used to explain the detrimental effect of sulfur-metabolizing microbes on the incidence of EC. (1) DNA damage: Gut microbes can regulate the bile acid metabolism through different hydrolase enzyme activities, whereas the dysregulation of intestinal microbiota could lead to an increase in deoxycholate secretion, which induces DNA damage [30]. High concentrations of H2S, as the main metabolite of sulfur-metabolizing microbes, can also cause DNA damage [31, 32]. (2) Altered host cell proliferation and death: Excessive H2S can diffuse into blood [33] and enter the esophageal tissue, where it promotes cell proliferation, anti-apoptosis, and angiogenesis by the up-regulation of HSP90, which causes cancerization and migration of cells [34]. (3) Inflammation: The gut microbes and their metabolites promote inflammation. Some Gram-negative rods, such as E. coli, can induce chronic inflammation and promote a cascade of reactions leading to EC [35]. A few of the compounds like Lipopolysaccharide (LPS), activated the NF-κΒ signaling pathway, which led to an increase in the inflammatory cytokine levels [36]. The accumulation of inflammatory cytokine causes angiogenesis, cell proliferation and invasion, mutation, and finally tumor formation [37]. (4) Immune regulation: Massive accumulation of sulfur-metabolizing microbes and H2S lead to an increase in intestinal permeability, which allows the gut microbes to translocate into the body, and disrupt immunological homeostasis by inducing innate and adaptive immune responses [38,39,40] and affect the development of immune cells like neutrophils, T lymphocytes, B lymphocytes, etc [41]. The immune system can also be stimulated by the structural components of bacteria, such as flagellin, LPS, etc [42]. Interestingly, gut microorganisms can cause immunosuppression, which lowers anticancer immunity [43]. However, there is currently no research focusing on the mechanisms underlying the relationship between sulfur-metabolizing microbes, H2S and EC.

The SMD pattern showed a positive association with EC and ESCC, but only a statistically significant association between each 1 score increment of SMD and EA in our results. ESCC and EA are two common histological subtypes of EC, and they display considerable differences in pathogenesis, epidemiological characteristics, and other aspects [44]. ESCC is closely related to factors such as smoking, alcohol consumption, intake of hot foods, and chronic esophagitis, whereas EA is more closely related to gastroesophageal reflux disease, Barrett’s esophagus, and obesity. The incidence of ESCC is higher in Asian and African regions, while EA is more prevalent in Western countries. Our study population is based in the United States, and we only recorded 39 cases of ESCC, which may be related to the lower incidence of ESCC in Western countries. Moreover, this study aimed to explore the association between diet and EC, and previous research suggested that the link between ESCC and diet was more pronounced, which may explain why we found a positive correlation in ESCC but not in EA. Of course, given that we only recorded 39 cases of ESCC, we cannot dismiss the possibility that this is a chance finding, and larger population studies are required to confirm our conclusions.

In our subgroup analyses, we found a stronger inverse correlation between SMD score and EC incidence in participants without regular consumption of aspirin. In fact, as early as 2003, Douglas A Corley et al. discovered the protective effect of aspirin on EC [45]. Their meta-analysis results showed that aspirin/NSAIDs could reduce the risk of EC by 43%. In addition, they found that regular use of aspirin was associated with a lower risk of EC compared to intermittent use. The possible mechanisms include: (1) Aspirin can inhibit the activity of cyclooxygenase-2 (COX-2), which act as Prostaglandin Synthetase and is highly expressed in EC tissue and involved in some key cellular activities such as cell proliferation and apoptosis [46]; (2) Aspirin can promote tumor apoptosis through activation of the NF-κB signaling pathway or upregulation of anti-cancer gene expression [46, 47]; (3) Aspirin can regulate human gut microbes: increase beneficial bacteria and reduce pathogenic bacteria, such as Bacteroides [48]. Therefore, in populations using aspirin regularly, the adverse effects of SMD on EC may be counteracted by the action of aspirin, which needs more research to testify.

A major strength of this study is that we firstly estimate the correlation between SMD (which is a microbe-associated dietary pattern) and the risk of EC. This study offered additional insights into the pathogenesis of EC. Secondly, the data collection instrument used for collecting the dietary data was well-validated. As a prospective designed cohort analysis, the recall and selection bias were minimized. Thirdly, by focusing on dietary patterns rather than specific food items, the interactions between foods could be taken into consideration, and the probability of accidental statistical significance was reduced. Lastly, we could adjust for multiple confounding factors in the prospective cohort study.

Despite the above superiorities, this study exhibited a few limitations. Firstly, a limited number of EC patients were studied in this study, there were only 41 cases of ESCC and 97 cases of EA. There were limited data regarding the molecular subtypes, which affected our ability to determine the associations between different subtypes and the robustness of the statistical outcomes. Secondly, all participants in this study were American and aged more than 55, which affected the generalization of the findings. Thirdly, no study has determined the probable mechanism between the SMD, sulfur-metabolizing microbes and EC to date. Finally, many studies have already confirmed the impact of cooking methods and temperatures on EC [49, 50], relevant data was lack in our study, so we cannot take it into consideration. Further researches are needed to fill these gaps.

Conclusion

In conclusion, our results indicated positive associations between SMD pattern and EC, as well as ESCC, and the association between SMD and EC was more pronounced in participants with no regular consumption of aspirin. Therefore, avoiding SMD pattern may be beneficial for EC prevention.

Data availability

The raw data is unavailable due to the National Cancer Institute’s data policy. Please contact the National Cancer Institute by mail if you want access to the dataset.

Abbreviations

SMD:

Sulfur microbial diet

EC:

Esophageal cancer

ESCC:

Esophageal squamous cell carcinoma

EA:

Esophageal adenocarcinoma

BMI:

Body mass index

DHQ:

Dietary history questionnaire

BQ:

Baseline questionnaire

SQX:

Supplemental questionnaire

HRs:

Hazard ratios

CIs:

Confidence intervals

NCI:

National cancer institute

PLCO:

Prostate lung colorectal and ovarian

SD:

Standard deviation

H2S:

Hydrogen sulfide gas

E. coli:

Escherichia coli

LPS:

Lipopolysaccharide

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Acknowledgements

All authors sincerely thank the PLCO study team and the National Cancer Institute for access to data collected by the PLCO trial.

Funding

This work was supported by 2018 Medical Research Project of Chongqing Health Commission and Chongqing Science and Technology Commission (No. 2018MSXM079), The General Project of Chongqing Natural Science Foundation, Chongqing Science and Technology Commission, China [cstc2021jcyj-msxmX0153], [cstc2021jcyj-msxmX0112], and [CSTB2022NSCQ-MSX1005], and Kuanren Talents Project of the Second Affiliated Hospital of Chongqing Medical University in China [kryc-yq-2110].

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  1. Xiaorui Ren and Li Xin contributed equally to this work.

Authors and Affiliations

  1. Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, No.288 Tianwen Avenue, Nan’an District, Chongqing, 400010, China

    Xiaorui Ren, Li Xin, Linglong Peng, Yi Xiao, Haoyun Luo, Zhiyong Zhu, Qi Wei, Yahui Jiang, Hongmei He, Yaxu Wang, Yunhao Tang & Haitao Gu

  2. Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China

    Zhihang Zhou

  3. Department of Clinical Nutrition, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China

    Ling Xiang

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  1. Xiaorui Ren
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Contributions

XR, LX (Li Xin), YT, and HG contributed to the study design and data analysis. XR, and LX (Li Xin) contributed to the data interpretation and writing of the manuscript. XR, LP, YX, ZZ (Zhihang Zhou), HL, ZZ (Zhiyong Zhu), YJ, QW, HH, LX (Ling Xiang), YW, YT, and HG contributed to the data collection, and data curation of the present analysis. XR, and HG assisted with statistical analysis and the funding acquisition. All of the authors reviewed or revised the manuscript. All authors contributed to the article and approved the submitted manuscript. The work reported in the paper has been performed by the authors, unless clearly specified in the text.

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Correspondence to Yunhao Tang or Haitao Gu.

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12937_2024_1035_MOESM1_ESM.docx

Supplementary Material 1: Supplementary Table 1. Criteria for determining the sulfur microbial diet scores. Supplementary Table 2. Distribution of variables with missing data before and after imputation. Supplementary Table 3. The distribution of missing categories by sulfur microbial diet score. Supplementary Table 4. Association between sulfur microbial diet components (8 food groups) and the risk of esophageal cancer stratified according to their scores

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Ren, X., Xin, L., Peng, L. et al. Association between sulfur microbial diet and the risk of esophageal cancer: a prospective cohort study in 101,752 American adults. Nutr J 23, 139 (2024). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12937-024-01035-y

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Keywords

Nutrition Journal

ISSN: 1475-2891

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