Interactions between environmental factors and melatonin receptor type 1A polymorphism in relation to oral cancer susceptibility and clinicopathologic development

Abstract

Background: The purpose of this study was to explore the combined effect of melatonin receptor type 1A (MTNR1A) gene polymorphisms and exposure to environmental carcinogens on the susceptibility and clinicopathological characteristics of oral cancer.

Methodology and principal findings: Three polymorphisms of the MTNR1A gene from 618 patients with oral cancer and 560 non-cancer controls were analyzed by real-time polymerase chain reaction (PCR). The CTA haplotype of the studied MTNR1A polymorphisms (rs2119882, rs13140012, rs6553010) was related to a higher risk of oral cancer. Moreover, MTNR1A gene polymorphisms exhibited synergistic effects of environmental factors (betel quid and tobacco use) on the susceptibility of oral cancer. Finally, oral-cancer patients with betel quid-chewing habit who had T/T allele of MTNR1A rs13140012 were at higher risk for developing an advanced clinical stage and lymph node metastasis.

Conclusion: These results support gene-environment interactions of MTNR1A polymorphisms with smoking and betel quid-chewing habits possibly altering oral-cancer susceptibility and metastasis.

Fig 1. Melatonin receptor (MTNR) 1A gene, locations of the genotyped variants, and their pairwise linkage disequilibrium (LD) patterns.

Schematic presentation of the MTNR1A (gene ID: 4543) (A) indicating locations of the analyzed variants (rs2119882, rs13140012, and rs6553010), (B) the one observed haploblock, and the pairwise LD measure, D’. Black box, untranslated region; white box, coding region. The red color reveals the putative transcription factor binding sites.