Chronic candidosis and oral cancer in APECED-patients: Production of carcinogenic acetaldehyde from glucose and ethanol by Candida albicans
✍ Scribed by Johanna Uittamo; Emilia Siikala; Pertti Kaihovaara; Mikko Salaspuro; Riina Rautemaa
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- French
- Weight
- 79 KB
- Volume
- 124
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disease caused by mutations of the AIRE (autoimmune regulator) gene. [1][2][3] It is associated with a limited T lymphocyte defect and an autoimmune response to various tissues, particularly endocrine glands. It mainly causes a set of three abnormal features; chronic mucocutaneous candidosis, hypoparathyroidism and adrenal insufficiency. 4 Most patients have chronic oral candidosis since early childhood. Of all the APECED patients in Finland that are beyond the age of 25, 10% have developed oral or oesophageal carcinoma at the site of chronic mucositis. 5 It is the only malignancy diagnosed in these patients. The age at cancer diagnosis was markedly low (29-44 years), significantly lower than for oral or oesophageal squamous cell carcinoma in general. The pathogenetic mechanism behind APECED associated oral cancer has so far remained unclear. [6][7][8][9] The most important risk factors for upper digestive tract cancers are tobacco smoking, alcohol intake, and poor oral hygiene. [10][11][12] They all associate with increased acetaldehyde (ACH) levels in saliva, and there is strong evidence supporting the role of ACH as a common dominator. [13][14][15][16][17][18] The mechanism leading to increased ACH levels in saliva after alcohol consumption is local microbial ACH production, i.e. the oxidation of salivary ethanol (EtOH) to ACH by microbial alcohol dehydrogenase (ADH)-enzyme. [15][16][17] Previous studies have shown that Candida albicans can produce significant amounts of carcinogenic ACH in clinically relevant EtOH concentrations. 19 It has been demonstrated that polyamines are able to facilitate the formation of mutagenic DNA-adducts in biologically relevant ACH concentrations (50-100 lM). 14 The local in vivo carcinogenic effect of ACH is derived from epidemiological and biochemical studies on aldehyde dehydrogenase-2 (ALDH2)-deficient Asians. The mitochondrial ALDH2enzyme is responsible for most of the ACH oxidation to acetate. Among ALDH2-deficient subjects this enzyme is partly inactive, which results in the accumulation of ACH in saliva after alcohol drinking. 20 In Asian heavy drinkers ALDH2-deficiency is associated with a 10-fold risk of oral cancer when compared to those with the normal ALDH2-enzyme. 21 However, the relationship between glucose and ACH production by Candida albicans has not been investigated previously. C. albicans may play a role in metabolizing glucose into carcinogenic ACH in the mouth and could participate in the pathoge-