Reduced expression of hMLH1 and hGTBP/hMSH6: a risk factor for head and neck cancer

Abstract

Head and neck cancer, like lung cancer, is considered a paradigm of an environmentally induced disease. Genetically determined variation in DNA repair capacity is thought to contribute to susceptibility to tobacco-related cancers. In this molecular epidemiology study, we investigated the association between DNA mismatch-repair (MMR) gene expression and the risk of head and neck cancer. Using our newly developed multiplex reverse transcription-PCR assay, we simultaneously evaluated the relative expression levels of five MMR genes (hMSH2, hMLH1, hPMS1, hPMS2, and hGTBP/hMSH6) in the peripheral blood lymphocytes of 78 patients (mean age = 59.6 +/- 12.4 years) with newly diagnosed head and neck cancer and 86 healthy controls (mean age = 58.2 +/- 12.9 years). The relative MMR gene expression was not correlated with disease stage or tumor site in the cases or with smoking and alcohol use in the controls. The expression levels increased with age in both cases and controls, but the mean expression of hMLH1, hPMS1, and hGTBP/hMSH6 was significantly lower in the cases than in the controls (P < 0.05). Using the median expression level in controls as the cutoff value, significantly increased odds ratios (ORs) were associated only with low expression of hMLH1 (OR = 4.4; 95% confidence interval = 2.1-9.1) and hGTBP/hMSH6 (OR = 2.1; 95% confidence interval = 1.1-4.1) after adjustment for age, sex, ethnicity, smoking status, and alcohol use. The results suggest that low hMLH1 and hGTBP/hMSH6 expression is associated with an increased risk of head and neck cancer. Additional studies with a larger number of subjects are warranted to confirm these findings.