Metallothionein-1 genotypes in the risk of oral squamous cell carcinoma

Background: We conducted an independent analysis of metallothionein 1 (MT-1) rs8052394, rs11076161, rs8052334, rs964372, rs7191779, and rs708274 in 587 individuals who were either healthy controls or subjects with oral squamous cell carcinoma (OSCC). Methods: All participants provided a nucleic acid sample (blood) as well as epidemiologic information on covariates or "risk factors" for OSCC, including tobacco, alcohol, and areca quid use. The genotyping result was used in a logistic regression model that examined main effects as well as statistical interactions while controlling for confounders. Results: MT-1 is involved in regulation of zinc and copper homeostasis. It also is a potent antioxidant and its polymorphisms correlate with the risk for OSCC. Rs11076161 A, rs964372 C, and rs7191779 C alleles were protective against OSCC (adjusted OR = 0.53, 0.49, 0.36, respectively; p < 0.05), whereas rs8052394 A alleles were associated with increased risk. Areca quid chewing and tobacco use were strong risk factors for developing the disease and were associated with 20- and 8-fold increases in adjusted risk (p < 0.05), respectively. Conclusions: Controlling for the effects of age, gender, areca quid, tobacco, and alcohol use, individuals with inherited the MT-1 rs11076161 AA, rs964372 CC, and rs7191779 GC genotypes may experience significant protection against OSCC, whereas individuals carrying the MT-1 rs8052394 A allele seem exposed to higher risk.