Susceptibility associations of HLA class II gene polymorphisms in oral submucous fibrosis derived oral squamous cell carcinoma.

OBJECTIVE: This study aimed to explore associations between human leukocyte antigen (HLA) class II (DRB1, DQB1, DPB1) alleles and haplotypes and susceptibility to oral submucous fibrosis (OSF) and its progression to oral squamous cell carcinoma (OSCC).

METHODS: 54 OSF-derived OSCC patients, 53 OSF patients, and 56 healthy controls were enrolled. HLA class II genes were typed using polymerase chain reaction-sequence-specific primers (PCR-SSP). Allele and haplotype frequencies, as well as linkage disequilibrium (LD), were calculated. Allele and haplotype frequencies, as well as relative risks across groups, were compared.

RESULTS: 4 HLA class II alleles and 5 haplotypes were identified as associated with altered risks of OSCC and OSF. Compared to the controls, OSCC patients had lower frequencies of DPB1*02, DPB1*04, DPB1*05, DRB1*16-DPB1*02, and DRB1*16-DPB1*05, notably reducing the risk of OSCC (all OR < 1, P < 0.05), and a higher frequency of DRB1*14-DPB1*02, significantly increasing the risk of OSCC (OR > 1, P < 0.05). OSF patients had a higher frequency of DRB1*10, which was positively associated with OSF (OR > 1, P < 0.05). Compared to OSF patients, OSCC had lower frequencies of DRB1*10, DPB1*02, DPB1*04, and DPB1*05, showing a negative correlation with OSCC risk (all OR < 1, P < 0.05), and higher frequencies of DRB1*11-DQB1*06 and DRB1*14-DPB1*02, noticeably increasing the risk of OSCC (all OR > 1, P < 0.05).

CONCLUSIONS: This study suggests potential associations: HLA-DRB1*10, DPB1*02, DPB1*04, DPB1*05, DRB1*16-DPB1*02, and DRB1*16-DPB1*05 could potentially exert a protective effect against OSF-derived OSCC. In contrast, DRB1*14-DPB1*02 significantly increases the risk of OSCC, whereas DRB1*11-DQB1*06 and DRB1*14-DPB1*02 may promote progression from OSF to OSCC. Additionally, DRB1*10 is a potential susceptibility gene for OSF but may also inhibit progression from OSF to OSCC.