Association of NUCB2 genetic variants with the clinicopathological features of oral cancer

Oral cancer ranks as the fourth most common cancer among men in Taiwan and the ninth most common cancer among men worldwide. Nesfatin-1, an adipokine derived from the precursor NUCB2 gene, was originally discovered in hypothalamic neurons. The connections among lifestyle factors that promote cancer, NUCB2 polymorphisms, and oral cancer are still not well understood. We examined the association of four NUCB2 gene polymorphisms (rs1330, rs214101, rs757081, and rs10766383) and clinicopathological characteristics with oral cancer in Taiwanese men compared with healthy controls. According to our data, in patients aged ≥60 years, specific NUCB2 genotypes were significantly associated with more aggressive disease features. Compared with the wild-type C/C genotype, carriage of at least one polymorphic allele (T allele at rs1330 or G allele at rs757081) was correlated with an elevated risk of progression to stage III/IV disease. Furthermore, the GA/AA genotypes at rs214101 and the TG/GG genotypes at rs10766383 were associated with elevated risks of both advanced-stage (III/IV) disease and lymph node metastasis. Our findings suggest that NUCB2 SNPs may play a pivotal role in oral cancer progression and metastatic potential, particularly in older patients.