Association betweenSalmonellainfection and colon cancer: a nationwide registry-based cohort study

Janneke W Duijster,Eelco Franz,Jørgen V Hansen,Jacques J C Neefjes,Steen Ethelberg,Morten Frisch,Lapo Mughini-Gras

doi:10.1017/s0950268821000285

Abstract

Laboratory data increasingly suggest that Salmonella infection may contribute to colon cancer (CC) development. Here, we examined epidemiologically the potential risk of CC associated with salmonellosis in the human population. We conducted a population-based cohort study using four health registries in Denmark. Person-level demographic data of all residents were linked to laboratory-confirmed non-typhoidal salmonellosis and to CC diagnoses in 1994-2016. Hazard ratios (HRs) for CC (overall/proximal/distal) associated with reported salmonellosis were estimated using Cox proportional hazard models. Potential effects of serovar, age, sex, inflammatory bowel disease and follow-up time post-infection were also assessed. We found no increased risk of CC ≥1 year post-infection (HR 0.99; 95% confidence interval (CI) 0.88-1.13). When stratifying by serovar, there was a significantly increased risk of proximal CC ≥1 year post-infection with serovars other than Enteritidis and Typhimurium (HR 1.40; 95% CI 1.03-1.90). CC risk was significantly increased in the first year post-infection (HR 2.08; 95% CI 1.48-2.93). The association between salmonellosis and CC in the first year post-infection can be explained by increased stool testing around the time of CC diagnosis. The association between proximal CC and non-Enteritidis/non-Typhimurium serovars is unclear and warrants further investigation. Overall, this study provides epidemiological evidence that notified Salmonella infections do not contribute significantly to CC risk in the studied population.

Highlights

Colon cancer (CC) is the third most common cancer in industrialised countries, with 1.1 million new diagnoses annually worldwide [1]
Among those with a CC diagnosis, 278 individuals were diagnosed with CC after salmonellosis, of which 33 occurred within the first year post-infection
The risk of CC in individuals with reported salmonellosis was compared to the risk in individuals without a reported salmonellosis, accounting for potential confounding and modifying effects of age, sex, inflammatory bowel disease (IBD) and follow-up time post-infection

Summary

Introduction

Colon cancer (CC) is the third most common cancer in industrialised countries, with 1.1 million new diagnoses annually worldwide [1]. Several mechanisms have been identified through which bacteria can contribute to cancer formation These include chronic inflammation, production of DNA-damaging toxins and manipulation of host cell signalling pathways [3, 4, 6]. Salmonella is expected to contribute to carcinogenesis mainly under conditions of longlasting infections, an intact bacterial type 3 secretion System (T3SS), and with a background of host predisposition, in which significant numbers of pre-transformed cells are present in the intestine. This has been shown in vivo by experiments demonstrating a higher risk of colon carcinoma formation after infection with wild type vs ΔprgH mutant S. Typhimurium (lacking the T3SS) strains in mice genetically predisposed to cancer (APC+/−) vs. normal mice [4]

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Results

Conclusion