HLA-DQB1*05:02: A Novel Genetic Marker for Susceptibility to Oral Cavity Squamous Cell Carcinoma

INTRODUCTION: Environmental exposure to carcinogens causes mucosal damage in the upper aerodigestive tract and can lead to cancers. The susceptibility to carcinogens varies between individuals. To identify susceptibility genes in head and neck cancers, we enrolled patients with early-onset disease and analyzed them by genome-wide association study.

METHODS AND MATERIALS: This case-control study included 54 young male patients with oral squamous cell carcinoma (OSCC) who were treated between March 1996 and December 2016, as well as 2400 healthy controls. A single nucleotide polymorphism (SNP) array was used to determine genetic loci that increase susceptibility to OSCC. In another validation cohort, sequencing-based typing (TBG Biotechnology Corp., Taipei, Taiwan) was used to determine the HLA-DQB1 genotype in another 100 OSCC patients.

RESULTS: We analyzed the allele frequencies of 664,994 autosomal SNPs in 54 OSCC cases. In a genome-wide association analysis, four SNPs on chromosomes 6, 7, 9, and 12 were significantly different between OSCC patients and controls (corrected p < 1.0 × 10 -6). HLA-DQB1 was closest to rs28451423 on chromosome 6. In the validation cohort, HLA-DQB1*05:02 in OSCC (18.5%) was significantly different from the normal population (7.0%) (p = 0.009). The influence of disease onset was independently significant after adjusting smoking, alcohol drinking, and areca-quid chewing (p = 0.015, OR: 3.922, 95% confidence interval: 1.311-11.734). Furthermore, HLA-DQB1*05:02 was associated with early-onset OSCC (p = 0.004).

CONCLUSION: HLA-DQB1*05:02 increases individuals' risks of OSCC independent of environmental exposures, particularly in cases of early-onset OSCC. This study provides a genetic basis and disease marker for personalized prevention of OSCC.