Background: Squamous cell carcinoma of the head and neck (SCCHN) is one of the most common cancers worldwide and includes cancers arising from the oral cavity, pharynx and larynx. Genome-wide association studies have found several genetic variants related to the risk of SCCHN; however, they could only explain a small fraction of the heritability. Thus, more susceptibility loci associated with SCCHN need to be identified.
Methods: An association study was conducted by genotyping 555 patients with SCCHN and 1367 controls in a Chinese population. Single-variant association analysis was conducted on 63 373 SNPs, and the promising variants were then confirmed by a two-stage validation with 1875 SCCHN cases and 4637 controls. Bioinformatics analysis and functional assays were applied to uncover the potential pathogenic mechanism of the promising variants and genes associated with SCCHN.
Results: We first identified three novel genetic variants significantly associated with the risk of SCCHN (p=7.45×10-7 for rs2517611 at 6p22.1, p=1.76×10-9 for rs2524182 at 6p21.33 and p=2.17×10-10 for rs3131018 at 6p21.33). Further analysis and biochemical assays showed that rs3094187, which was in a region in high linkage disequilibrium with rs3131018, could modify TCF19 expression by regulating the binding affinity of the transcription factor SREBF1 to the promoter of TCF19. In addition, experiments revealed that the inhibition of TCF19 may affect several important pathways involved in tumourigenesis and attenuate the cell proliferation and migration of SCCHN.
Conclusion: These findings offer important evidence that functional genetic variants could contribute to development of SCCHN and that TCF19 may function as a putative susceptibility gene for SCCHN.
Keywords: genetic variation; genetics; genotype; nucleic acid amplification techniques.
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