Severe Salmonella spp. or Campylobacter spp. Infection and the Risk of Biliary Tract Cancer: A Population-Based Study

Abstract

Salmonella spp. infection has shown to have oncogenic transformative effects and thereby increases the risk of certain cancers. For Campylobacter spp., similar effects have been demonstrated. Risk factor identification may allow for timely diagnosis and preventive treatment. To substantiate the oncogenic potential of Salmonella and Campylobacter spp., this study compared the incidence of extrahepatic biliary tract cancer (BTC) in patients with diagnosed Salmonella or Campylobacter spp. infection with BTC incidence in the Netherlands. National infectious diseases surveillance records of patients diagnosed with a laboratory-confirmed Salmonella or Campylobacter spp. infection during 1999–2016 were linked to the Netherlands Cancer Registry. Incidence of BTC in Salmonella and Campylobacter spp. patients was compared to the incidence of BTC in the general population using Standardized Incidence Ratios (SIRs). In total, 16,252 patients were diagnosed with Salmonella spp. and 27,668 with Campylobacter spp. infection. Nine patients developed BTC at a median of 46 months (13–67) after Salmonella spp. infection and seven at a median of 60 months (18–138) after Campylobacter spp. infection. SIR of BTC in salmonellosis patients was 1.53 (95% CI 0.70–2.91). In patients aged <60 years, the SIR was 1.74 (95% CI 0.36–5.04). For campylobacteriosis patients, the SIR was 0.97 (95% CI 0.39–2.00). Even though Salmonella or Campylobacter spp. infection was not significantly associated with increased BTC risk in this cohort, it remains extremely important to study potential risk factors for cancer to facilitate screening and ultimately improve prognosis of cancer patients.

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

“…CDT causes double-stranded DNA breaks that may contribute to cancer formation ( He et al, 2019 ). In Supplementary Table 4 nine epidemiological studies are summarized which assess the association between Campylobacter and GI cancer ( Brauner et al, 2010 ; Blackett et al, 2013 ; Wu et al, 2013 ; Allali et al, 2015 ; Alexander et al, 2016 ; Mughini Gras, 2017 ; De Savornin Lohman et al, 2020 ; Wang et al, 2020 ; Wei et al, 2020 ). In humans, Campylobacter spp.…”

“…Three cohort studies assessed the association between Campylobacter infection and risk of colon cancer (CC), biliary tract cancer or multiple types of cancer later in life. All three studies used a follow-up time of more than 10 years ( Supplementary Table 4 ; Brauner et al, 2010 ; Mughini Gras, 2017 ; De Savornin Lohman et al, 2020 ). None of the studies found a significantly increased risk of digestive cancer after infection compared to the general population, all with standardized incidence ratios (SIRs) below or close to 1.…”

“…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 ).…”

“…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).…”

The Role of Cyclomodulins and Some Microbial Metabolites in Bacterial Microecology and Macroorganism Carcinogenesis

“…The most studied in the context of association with oncological diseases is the intestinal microbiota. [ 17 , 18 , 19 ].…”