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Background: Melatonin, produced by the pineal gland, is known for its antioxidant, oncostatic, and anti-inflammatory properties. However, studies on serum melatonin levels in different cancer types have yielded conflicting results, and little is known about the clinical significance of serum melatonin in oral squamous cell carcinoma (OSCC) in the Southern Asian population. Therefore, we explored its role in OSCC in this study. Methods: A total of 67 male OSCC patients and 78 healthy controls were enrolled in this case–control study. The serum levels of melatonin were determined by enzyme-linked immunosorbent assay (ELISA) and compared between the two groups. Results: The serum melatonin levels were significantly lower in OSCC patients compared with healthy controls (mean ± standard deviation, 15.0 ± 4.6 vs. 18.5 ± 11.8 pg/mL, p = 0.02). In the subgroup of age less than 55 years (mean age of OSCC), OSCC patients had a significantly decreased melatonin level than healthy controls (mean melatonin, 15.7 ± 12.6 vs. 20.8 ± 3.9 pg/mL, p = 0.02). Decreased serum melatonin (odds ratio (OR): 0.95, 95%CI: 0.91–0.99), alcohol consumption (OR: 29.02, 95%CI: 11.68–72.16), betel quid chewing (OR:136.44, 95%CI: 39.17–475.27), and cigarette smoking (OR:29.48, 95%CI: 11.06–78.60) all increased the risk of OSCC under univariate analyses of logistic regression. Betel quid chewing (OR: 45.98, 95%CI: 10.34–204.49) and cigarette smoking (OR:6.94, 95%CI: 1.60–30.16) were the independent risk factors for OSCC in Taiwan. In addition, a negative correlation between age and melatonin level was observed in healthy controls (Pearson r = −0.24, p = 0.03). However, the negative correlation was lost in patients with OSCC. Melatonin concentration had no association with the severity of OSCC. Conclusion: Overall, our study provides evidence that serum melatonin levels decreased in OSCC patients in Taiwan and the decreased level is much significant in young populations and suggests that the decreased melatonin was associated with OSCC, especially in young populations. Further studies are warranted to investigate whether melatonin can be a useful non-invasive screening tool for OSCC.

Decreased Circulating Melatonin with Loss of Age-Related Biphasic Change in Patients with Oral Squamous Cell Carcinoma