Influential factors on tumor recurrence in head and neck cancer patients.

Alcohol consumption and cigarette smoking play a key role in the development and progression of head and neck cancer. Additionally, epidemiologic studies have given evidence that other environmental and genetic factors are relevant. We present a prospective study including 465 head and neck cancer patients. All patients were recruited between 1994 and 1998 during the initial tumor diagnosis. Three hundred twelve patients could be followed over 5 years after histologically proven curative surgical treatment. All clinical data were recorded (i.e., age, gender, TNM stage, histological grading, smoking and drinking habits) and genetic variations at loci encoding detoxifying enzymes (glutathione S-transferase and cytochrome P450); immune modulating cytokines (tumor necrosis factor) and cell cycle regulating proteins (cyclin D1) were determined. Parameters with an impact on recurrence-free survival were analyzed. A strong influence could be attributed to the tumor size at the time of presentation. Additionally, the grading of the tumor showed a strong influence (5 years recurrence free: G1: 87% and G1: 61%). Furthermore, it could be shown that the recurrence-free survival was significantly influenced by cyclin D1 genotypes (CCND1GG: P =0.01; HR=3.72) and TNF microsatellite haplotypes (TNFB1D5: P =0.043; HR=2.05). These findings are compatible with the view that genetic predisposition is important in determining recurrence-free survival after surgical treatment of head and neck cancer.