Reduced mRNA expression of nucleotide excision repair genes in lymphocytes and risk of squamous cell carcinoma of the head and neck

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Nucleotide excision repair (NER) plays a critical role in the development of smoking-related cancers. We hypothesize that mRNA expression levels of NER genes are associated with risk of the squamous cell carcinoma of head and neck (SCCHN). To test this hypothesis, we conducted a case-control study of 260 SCCHN patients and 246 cancer-free controls by measuring the mRNA expression levels of eight core NER genes in cultured peripheral lymphocytes. Compared with the controls, cases had statistically significantly lower expression levels of <span style="font-style:italic;">DDB1</span> and <span style="font-style:italic;">ERCC3</span> (<span style="font-style:italic;">P</span> = 0.015 and 0.041, respectively). Because <span style="font-style:italic;">DDB1</span> and <span style="font-style:italic;">ERCC3</span> expression levels were highly correlated, we used <span style="font-style:italic;">DDB1</span> for further multivariate analyses and modeling. After dividing the subjects by controls’ quartiles of expression levels, we found an association between an increased risk of SCCHN and low <span style="font-style:italic;">DDB1</span> expression levels [adjusted ORs and 95% CIs: 1.92 and 1.11–3.32, 1.48 and 0.85–2.59, 2.00 and 1.15–3.45 for the 2^nd–4^th quartiles, respectively, compared with the 1^st quartile; <span style="font-style:italic;">P</span>_trend = 0.026]. We also identified a multiplicative interaction between sex and <span style="font-style:italic;">DDB1</span> expression levels (<span style="font-style:italic;">P</span> = 0.007). Finally, the expanded model with gene expression levels, in addition to demographic and clinical variables, on SCCHN risk was significantly improved, especially among men. In conclusion, reduced <span style="font-style:italic;">DDB1</span> expression levels were associated with an increased risk of SCCHN. However, these results need to be validated in larger studies.</span>

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