A Molecular Case-Control Study on the Association of Melatonin Hormone and rs#۱۰۸۳۰۹۶۳ Single Nucleotide Polymorphism in its Receptor MTNR۱B Gene with Breast Cancer

Background: The main function of the pineal hormone melatonin which is mediated via its two receptors, MTNR۱A and MTNR۱B, is to mediate dark signals in addition to anti-oxidation, immune system enhancement, protection from radiation, and anti-cancer functions. A common single nucleotide polymorphism in the MTNR۱B gene is rs#۱۰۸۳۰۹۶۳, which is well known as a risk factor for type ۲ diabetes mellitus. This study intends to figure out the role of melatonin and its receptor MTNR۱B gene rs#۱۰۸۳۰۹۶۳ polymorphism in breast cancer incidence, diagnosis and prognosis.Methods: This study included ۴۳ females with breast cancer and ۴۵ apparently normal healthy females. Restriction fragment length polymorphism-PCR was used for amplification and genotyping of the MTNR۱B gene rs#۱۰۸۳۰۹۶۳ polymorphism in whole blood. Serum melatonin levels were measured using a ready-for-use radioimmunoassay kit. Results: For the MTNR۱B gene rs#۱۰۸۳۰۹۶۳ polymorphism, we observed a significantly higher GG genotype frequency among cases (۷۲.۱%) than controls (۱۳.۳%), with a diagnostic sensitivity of ۸۳.۷۸% and specificity of ۷۶.۴۷%. The cases had a frequency of ۱۱.۶% for the CC genotype and ۱۶.۳% for the CG genotype which was significantly lower compared to controls that had a ۴۴.۴% frequency of the CC genotype and ۴۲.۲% frequency of the CG genotype. The GG genotype had a significant association with larger tumor volume (P=۰.۰۴۸). Serum melatonin levels were significantly lower among breast cancer patients than controls. Using the ROC curve analysis, serum melatonin showed a significant AUC (۷۲.۶%, P۳۹.۵ pg/ml.Conclusion: The risk for breast cancer incidence increased as the serum levels of melatonin decreased and in females homozygous for the G allele (GG genotype) of the MTNR۱B gene rs#۱۰۸۳۰۹۶۳ polymorphism. The GG genotype was found to be associated with increased breast tumor volume as a marker of a poor prognosis breast cancer.