The interleukin-8 (-251A/T) polymorphism is associated with increased risk for oral squamous cell carcinoma

Aims: In light of recently found contribution of angiogenic and inflammation-related factors to malignancies, this study investigated the possible association of interleukin-8 gene (IL-8) to increased risk of oral cancer. Methods: The IL-8 (-251A/T) polymorphism, which influences IL-8 gene expression, was evaluated by restriction fragment length polymorphism analysis in DNA samples of 158 German and Greek patients with oral squamous cell carcinoma and 156 healthy controls of equivalent sex, ethnicity and age. Results: Significant increase of mutant (A-251) allele, which results in higher IL-8 gene expression, was observed in all patients in comparison to normal controls (P < 0.001). The A/T heterozygotes had a two-fold greater risk (odds ratio 1.76, CI 1.11-2.79) for developing oral cancer compared to normal TT homozygotes. Furthermore, significantly increased values of mutant allele frequencies compared to controls were observed in all patients as well as in subgroups of patients with or without positive history of cancer (P < 0.05 and P < 0.001, respectively) and with or without positive history of thrombophilia (P < 0.05 and P < 0.001, respectively). Conclusions: In light to known observations of elevated plasma levels of IL-8 in several types of cancer including oral squamous cell carcinoma, the findings of this study suggest that the mutant allele of the (-251A/T) polymorphism may be a major contributing genetic factor to risk for oral cancer.