Due to impaired oesophageal motility and chronic accumulation of food residues, Candida fungi find favourable growth conditions in the oesophagus in achalasia. A team at the Erasmus Medical Centre in Rotterdam has now investigated in one of the largest achalasia cohorts how often Candida infection occurs and what influence this has on the risk of cancer.
The retrospective study included 234 achalasia patients who were followed up for a median of 13 years. In 29 of these individuals (12%), Candida infection of the oesophagus was detected at least once during follow-up. The retrospective study included 234 achalasia patients who were followed up for a median of 13 years. Twenty-nine of these individuals (12%) were diagnosed with Candida oesophagitis at least once during the study period. During the same period, 24 individuals (10%) developed oesophageal carcinoma.
The evaluation showed that a Candida infection of the oesophagus is associated with a dramatically increased risk of carcinoma. Candida oesophagitis as an independent factor for the development of malignant disease was associated with a hazard ratio of 8.24 (95% confidence interval 2.97–22.89). This corresponds to an eightfold increase in the risk of developing oesophageal cancer. The association was particularly evident in squamous cell carcinoma of the oesophagus, where the risk was increased by a factor of 13.6 when Candida was detected. Other risk factors such as age and gender also had an influence in the analysis. Higher cancer rates were found in older and male patients. However, the effect of Candida infection was significantly more pronounced.
But why could fungal colonisation promote the development of oesophageal cancer? Candida species are part of the natural microflora, but can become invasive and exacerbate inflammatory processes when the barrier function is impaired. They are also capable of producing potentially carcinogenic substances such as acetaldehyde from alcohol and nitrosamines from precursor compounds. Such substances are considered relevant carcinogens in the upper gastrointestinal tract. It is suspected that Candida infections could contribute to carcinogenesis through these effects or through chronic mucosal irritation or increased immune activation in achalasia.
Data on classic risk factors such as alcohol and tobacco consumption were not available in the present study. Nevertheless, it is striking that men in particular had a significantly increased risk of cancer – a patient group that is considered to be at particular risk for oesophageal carcinoma, even independently of achalasia. The reason for this is thought to be that men tend to consume more alcohol and tobacco. Whether Candida acts as an additional, possibly mediating factor here or is merely a marker for an increased level of inflammation remains open.
The results provide valuable information for clinical practice: Candida infection of the oesophagus in achalasia could be a potential risk factor for the development of oesophageal cancer. Whether there is actually a causal link should be investigated further in future studies.