Previous studies have documented that both vitamin D deficiency and single nucleotide polymorphism (SNPs) of genes responsible for mediating downstream effects of melatonin with development of breast cancer. In India 70 percent of the population suffers from Vitamin D deficiency. There are no available reports on association of vitamin D and SNPs in Melatonin genes towards development of breast cancer in Indian population.
To this end, we evaluated 50 vitamin D-deficient breast cancer subjects and studied the gene expression patterns and SNPs of melatonin receptor genes (MTNR1a, MTNR1b) and Arylalkylamine N-acetyltransferase (AANAT). Age matched breast cancer patients without Vitamin D deficiency and age matched normal subjects (i.e without breast cancer served as control).
Vitamin D-deficient studies demonstrated decreased expression MTNR1a, MTNR1b, and AANAT genes in vitamin D deficient breast cancer group as compared to subjects with normal vitamin D level (68% Vs 41%, p<0.001). Two two-staged analysis of genome-wide association (GWAS) showed association of MTNR1a, MTNR1b SNPs with cancer progression and metastasis in vitamin D deficient group. Interestingly the incidence of SNPs was 32% more in vitamin D-deficient breast cancer group when compared with the other groups.
Our pilot studies highlight the fact that both Vitamin D and products of melatonin have strong correlation with development of breast cancer and its invasiveness. Significant increase in SNPs of melatonin related genes under conditions of vitamin D insufficiency leads us to the contention that vitamin D and melatonin have additive effect in development of breast cancer. These experiments when repeated using large sample size coupled with animal studies in melatonin receptor knockout mice with breast cancer against vitamin D background can shed more light on the exact mechanism.
Raktim Mukherjee, Megha Dave, Vishnu Priya Veeraraghavan, Selvaraj Jayaraman.
Has not received any funding.
The author has declared no conflicts of interest.