Functional variant of CHI3L1 gene is associated with neck metastasis in oral cancer

Objectives: Oral cancer is the most common head and neck malignancy, and it is associated with a high recurrence rate and lymph node metastasis potential. YKL-40, also known as chitinase-3-like protein 1 (CHI3L1), is a secreted glycoprotein that serves as a biomarker in several diseases. It also plays a crucial role in regulating many characteristics of cancer, such as cell growth, migration, anti-apoptosis, and angiogenesis. Accumulating evidence supports the link between single-nucleotide polymorphisms (SNPs) and oral cancer, but no report on the association between CHI3L1 polymorphisms and oral cancer is available. Thus, the present study evaluated the contribution of CHI3L1 SNPs to oral cancer susceptibility and clinicopathology. Materials and methods: This study recruited a total of 2362 subjects, comprising 1190 healthy male controls and 1172 male patients with oral cancer. Allelic discrimination of the CHI3L1 polymorphisms − 1371 G>A (rs6691378), − 247 G>A (rs10399805), − 131 C>G (rs4950928), and + 2950 T>C (rs880633) was assessed through real-time polymerase chain reaction. Results: We detected a significant association of rs10399805 and rs6691378 with the risk of oral cancer (AOR, 1.537; 95% CI, 1.089–2.168; p = 0.014; AOR, 1.561; 95% CI, 1.131–2.156; p = 0.007, respectively) after adjustment for three potential confounders, smoking, betel nut chewing, and alcohol consumption. Moreover, we found that oral cancer patients carrying the homozygous A/A genotype of the rs10399805 (p = 0.035) or rs6691378 polymorphism (p = 0.023) showed a significantly lower risk of lymph node metastasis. Moreover, according to the Genotype-Tissue Expression database, the rs10399805 and rs6691378 polymorphisms in the promoter region were associated with decreased levels of CHI3L1 mRNA. Conclusions: In conclusion, we found that the homozygous mutant allele of rs10399805 and rs6691378 appeared to have significantly lower risk of lymph node metastasis and associated with its mRNA levels in oral cancer. Clinical relevance: The CHI3L1 polymorphisms rs10399805 and rs6691378 may act as biomarkers for predicting lymph node metastasis in oral cancer patients.