The Val allele of HER-2 codon 655 predicts the progression of oral squamous cell carcinoma.

ABSTRACT

HER-2 proto-oncogene is important for oral carcinogenesis. HER-2 codon 655 polymorphism, either isoleucine (Ile ATC) or valine (Val GTC), was associated with the risk of breast carcinoma. This study investigated the clinicopathological implications of this polymorphism in oral carcinoma. We found that 79% of oral carcinoma patients had A/A (Ile/Ile) genotype and 21% had A/G (Ile/Val) genotype, with a G (Val) allelic frequency of 0.10. Univariate analysis indicated a significantly higher Val allelic frequency in cases having nodal metastasis or tumor recurrence; and Val allele was associated with poorer recurrence-free survival of patients. Multivariate analysis after adjusting confounding factors by logistic regression analysis indicated that patients carrying Val allele had a 8.79- and 4.25-fold higher risk for nodal metastasis and recurrence, respectively. Using Cox proportional hazard model, the risk of tumor recurrence was 3.35-fold higher in patients carrying Val allele. This is the first report demonstrating that the Val allele of HER-2 codon 655 could be an independent predictor for oral carcinoma progression.