Author/Authors :
Abd El-Moneim، Nadia Ahmed نويسنده Department of Cancer Management and Research, Medical Research Institute, Alexandria University, Alexandria, Egypt , , Masry، Hisham El نويسنده Department of Biotechnology, Institute of Graduate Studies and Research, University of Alexandria, Alexandria, Egypt , , Sorial، Mina Mamdouh نويسنده Department of Biotechnology, Institute of Graduate Studies and Research, University of Alexandria, Alexandria, Egypt , , Hewala، Taha I. نويسنده Department of Radiation Science, Medical Research Institute, Alexandria University, Alexandria, Egypt , , Embaby، Amira نويسنده Department of Biotechnology, Institute of Graduate Studies and Research, University of Alexandria, Alexandria, Egypt , , Sheweita، Salah نويسنده Department of Biotechnology, Institute of Graduate Studies and Research, University of Alexandria, Alexandria, Egypt ,
Abstract :
Background: The main function of the pineal hormone melatonin which is mediated
via its two receptors, MTNR1A and MTNR1B, 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 MTNR1B gene is
rs#10830963, which is well known as a risk factor for type 2 diabetes mellitus. This study
intends to figure out the role of melatonin and its receptor MTNR1B gene rs#10830963
polymorphism in breast cancer incidence, diagnosis and prognosis.
Methods: This study included 43 females with breast cancer and 45 apparently normal
healthy females. Restriction fragment length polymorphism-PCR was used for amplification
and genotyping of the MTNR1B gene rs#10830963 polymorphism in whole blood. Serum
melatonin levels were measured using a ready-for-use radioimmunoassay kit.
Results: For the MTNR1B gene rs#10830963 polymorphism, we observed a
significantly higher GG genotype frequency among cases (72.1%) than controls (13.3%),
with a diagnostic sensitivity of 83.78% and specificity of 76.47%. The cases had a
frequency of 11.6% for the CC genotype and 16.3% for the CG genotype which was
significantly lower compared to controls that had a 44.4% frequency of the CC genotype
and 42.2% frequency of the CG genotype. The GG genotype had a significant association
with larger tumor volume (P=0.048). Serum melatonin levels were significantly lower
among breast cancer patients than controls. Using the ROC curve analysis, serum
melatonin showed a significant AUC (72.6%, P < 0.001) with diagnostic sensitivity of
91.1% and specificity of 58% at a cut-off level of 39.5 pg/ml. Females with serum
melatonin levels ?39.5pg/ml were at significantly increased risk for breast cancer
incidence by about 15 times more than females with levels > 39.5 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
MTNR1B gene rs#10830963 polymorphism. The GG genotype was found to be associated
with increased breast tumor volume as a marker of a poor prognosis breast cancer.
