The potential role of nontyphoidal salmonellosis in gastric cancer: a nationwide matched cohort study

Abstract

BackgroundThe research is to explore the association between nontyphoidal salmonellosis (NTS) and subsequent gastric cancer. Methods We conducted a retrospective study by analyzing hospitalization dataset from the National Health Insurance Research Database in Taiwan. Patients aged 20 years and older with NTS (n = 9 097) admitted between January 1, 2000, and December 31, 2012, were enrolled and followed up until December 31, 2013. The primary outcome was the incidence of gastric cancer. Cox proportional hazards regression was used to estimate the risk of malignancy, accounting for the competing risk of death. In addition, we conducted a sensitivity analysis by propensity score matching and exclusion of malignancy within 1 year observation to minimize measurable confounding and protopathic bias. Negative controls were applied to examine the presence of possible unmeasured confounders in the study. ResultsThe study included 18 194 patients (9097 in each NTS and non-NTS group). The median follow-up time was 7 years. The incidence density rate of gastric cancer was 0.72 per 1000 person-years for the NTS group and 0.40 per 1000 personyears for the non-NTS group. The NTS group had a modestly higher risk of gastric cancer (aHR, 2.02; 95% CI 1.18-3.45) than the non-NTS group. The sensitivity analyses revealed consistent results. Conclusions Patients with NTS are associated with increased risk of subsequent gastric cancer compared with non-NTS patients. Future research is needed to examine whether NTS is parallel, reactive or causative to gastric cancer.

Bacterial and Parasitic Pathogens as Risk Factors for Cancers in the Gastrointestinal Tract: A Review of Current Epidemiological Knowledge

“…enterica serotype Typhimurium in an experimental setting using murine gallbladder organoids ( Scanu et al, 2015 ). Seven epidemiological articles were found assessing the association between NTS infection and colorectal ( n = 3), CC ( n = 2), biliary tract cancer ( n = 2), and gallbladder, gastric, liver, and pancreatic cancer (latter four: n = 1) ( Supplementary Table 12 ; Kato et al, 2013 ; Iyer et al, 2016 ; Lu et al, 2017 ; Mughini-Gras et al, 2018 ; De Savornin Lohman et al, 2020 ; Chang et al, 2021 ; Duijster et al, 2021 ). The humoral immune response against Salmonella flagellin in CRC patients and individuals with colorectal polyps versus healthy controls was assessed in two different cohorts ( Supplementary Table 12 ; Kato et al, 2013 ).…”

“…Hence, this may dilute the observed effect of NTS in risk estimates including the older age groups. In a Taiwanese cohort, a HR of 1.03 (95% CI 0.72–1.47) was reported for the combined risk of colon and rectum cancer, while an over twofold significantly increased risk of GC was observed ( Supplementary Table 12 ; Chang et al, 2021 ). In addition, also an increased risk of developing biliary tract cancer after salmonellosis was reported in both a Dutch study (SIR: 1.53; 95% CI 0.70–2.91) and the Taiwanese cohort (HR: 2.23; 95% CI 0.83–6.05), though numbers were low in both studies ( De Savornin Lohman et al, 2020 ; Chang et al, 2021 ).…”

“…In a Taiwanese cohort, a HR of 1.03 (95% CI 0.72-1.47) was reported for the combined risk of colon and rectum cancer, while an over twofold significantly increased risk of GC was observed (Supplementary Table 12; Chang et al, 2021). In addition, also an increased risk of developing biliary tract cancer after salmonellosis was reported in both a Dutch study (SIR: 1.53; 95% CI 0.70-2.91) and the Taiwanese cohort (HR: 2.23; 95% CI 0.83-6.05), though numbers were low in both studies (De Savornin Lohman et al, 2020;Chang et al, 2021). Iyer et al (2016) demonstrated the presence of traces of S. Typhimurium in 12 out of 26 tumors from Indian gallbladder cancer patients (Supplementary Table 12; Iyer et al, 2016).…”

Risk of non‐typhoidal Salmonella infection in patients with cholecystectomy: Results from a nationwide matched cohort study in Taiwan

“…A matched control was assigned to each case with a cholecystectomy according to age, sex, index date, occupation and propensity score. We used the propensity score‐matching method to account for baseline differences 18 . The observed covariates in the logistic regression model to generate the propensity score were hypertension (ICD9 codes: 401‐405), diabetes (ICD9 code: 250), hyperlipidaemia (ICD9 codes: 272), coronary artery disease (ICD9 codes: 410‐414), cerebrovascular accident (430‐438), chronic kidney disease (ICD9 code: 585), chronic obstructive pulmonary disease (COPD, ICD9 codes: 491, 492 and 496), chronic liver diseases (ICD9 code: 571.4), autoimmune diseases (including systemic lupus erythematosus, ICD9 code: 710.0; ankylosing spondylitis, ICD9 code: 720.0; rheumatoid arthritis, ICD‐9‐CM code: 714.0; Sjögren's syndrome, ICD‐9‐CM code: 710.2), psoriasis (ICD9 code: 696), vasculitis (ICD9 code: 446) and inflammatory bowel disease (IBD, including Crohn's disease, ICD9 codes: 555.x and ulcerative colitis, ICD9 codes: 556.x).…”

Older veterans associated with reduced risk of cancer: Retrospective nationwide matched cohort study in Taiwan

“…NHIRD is available for research purposes with appropriate applications. The validity of NHIRD for use in epidemiological cancer research has been shown in the previous publication (17)(18)(19)(20)(21)(22)(23)(24). NHIRD includes patients treated at dedicated veterans' hospitals.…”