Fogorvosi szemle, 2007 (100. évfolyam, 1-6. szám)

2007-10-01 / 5. szám

FOGORVOSI SZEMLE ■ 100. évf. 5. sz. 2007. 250-257.

Semmelweis University Department of Oral and Maxillofacial Surgery Oral Pathology Unit, Budapest

Disorders of glucose metabolism and oral cancer risk

DR. ZSUZSANNA SUBA, DR. MÁRTA UJPÁL

Alcohol and tobacco are considered as major risk factors for oral cancer (OC). In the developed countries reduction of alcohol and tobacco consumption has achieved favorable decreasing trends in OC morbidity and mortality over the last decades. At the same time the earlier very high male-female OC ratio showed a declining tendency all over the world. This trend used to be simply interpreted by the increasing exposure to tobacco and alcohol among women. However, literary data support an enhanced prevalence of women among non-smoker non-drinker OC cases. These findings focused the attention for further underlying mechanisms in the initiation of OC, such as metabolic and hormonal disorders.

Insulin resistant states (metabolic syndrome and type-2 diabetes) are sources of many human diseases. Reactive hyperinsulinemia, increased production of insulin-like growth factors, hyperglycemia and its serious consequences are all proven cancer promoters. Decreased blood perfusion of the tissues caused by diabetic macro- and microvascular lesions, extracellular matrix alterations, and defects of inflammatory and immunologic reactions in type-2 diabetes are also predictors of OC.

The literary data and the authors’ own results on their OC cases support the strong association of type-2 diabetes and increased cancer risk. Moreover, type-2 diabetes has a significant impact on the local invasion and metastatic progression of OC.

The correlations between glucose metabolism disorders and malignancies reveal new possibilities in the prevention and treatment of OC.

Key words: oral cancer, risk factors, type-2 diabetes, insulin resistance

Introduction

Oral cancer (OC) is a serious and growing problem being the sixth most common malignancy in the world [10, 14, 32], Since alcohol and tobacco are considered to be major risk factors for OC, in the developed countries advantageous reduction of alcohol and tobacco consumption have achieved favorable decreasing trends in OC morbidity and mortality over the last decades [26]. However, persisting rises are continuously observed for most central and eastern European countries, reaching exceedingly high rates in Hungary [14],

Nowadays, after effective reduction of smoking and drinking habits, an increasing ratio of non-smoker nondrinker patients among OC cases has been observed in both the United States and Europe [47], At the same time the earlier very high male-female OC ratio showed a declining tendency all over the world. This trend used to be simply interpreted by the increasing exposure to tobacco and alcohol among women [14]. However, many literary data support an increased prevalence of women among non-smoker non-drinker OC cases [22, 30],

These recent findings suggest a possibility of further underlying changes in the initiation of OC besides smoking and drinking, and focus the attention on systemic OC risk factors, such as metabolic and hormonal disorders.

Impaired carbohydrate metabolism as a source of human diseases

Diabetes mellitus (DM) is a well-known complex metabolic disease, which affect not only the glucose metabolism but also lipid, protein and ion equilibrium. It is one of the leading causes of death and has a major contribution to hypertension, stroke, cardiovascular disease and kidney failure. The effect of DM on the oral health is also important as its untreated or latent forms may cause serious symptoms on the oral mucosa, especially gingival and periodontal complications [44].

Glucose metabolism disorders have several forms and stages. Type-1 diabetes (DM1) is mainly based on a defective insulin secretion, whereas the causal agent of the type-2 diabetes (DM2) is the defect of glucose uptake in the peripheral tissues. Intermediate metabolic stages, such as impaired glucose tolerance and impaired fasting glucose lie between normal glucose metabolism and manifested DM.

Reaven in 1988 demonstrated that the defective in-