Asian Research Thesis Index

Abstract

Vitamin D performs a vital role in normal and malignant cells proliferation and differentiation. Sufficient vitamin D status is crucial and beneficial for good health. It reduces the risk for bone disease, pain, autoimmune diseases, cancer, heart disease, mortality, and cognitive function. Epidemiologic and biological facts and figures suggest that vitamin D levels may influence breast cancer development. In body vitamin D activities are arbitrated through vitamin D receptor (VDR) and VDR gene polymorphisms are linked with the risk and progression of breast cancer. The present study is an endeavor to analyze vitamin D deficiency and its receptor gene polymorphism in 300 healthy and 300 women with breast cancer and also to determine the association between VDR genotype with breast cancer risk. In this study vitamin D deficiency was assessed by enzyme linked immunosorbant assay (ELISA).and serum calcium levels were estimated in both patients and control groups. VDR gene polymorphism was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequence analysis was also performed. Results concluded vitamin D deficiency in women with breast cancer whereas insufficiency in asymptomatic women. Low serum vitamin D and high calcium concentrations were significantly (p<0.001) associated with increased tumor size in patients. FokI genotypic frequency in healthy and breast cancer women was FF=55, Ff=3, ff=42, FF=46, Ff=10, and ff=44% whereas TaqI genotypic frequency was TT=15, Tt=65, tt=20, TT=20, Tt=53, and tt=27% respectively. Allelic frequency in healthy women was F=56, f =44, T=47.5, and t=52.5%, whereas in patients it was F=50.67, f=49.33, T=46.67, t=53.33%. In current study FokI and TaqI frequencies of controls and patients were compared with different populations by Chi2 test and a significant genotypic distribution difference of VDR gene (FokI, TaqI) polymorphism in Pakistani individuals was found. Vitamin D low levels were significantly associated (p<0.001) with both FokI and TaqI SNPs in present population. FokI and TaqI SNPs were significantly associated (P<0.001) with different age groups, tumor grade and ER/PR status of women with breast cancer. This study determined that vitamin D deficiency was more prevalent in patients than controls and vitamin D deficient women had 38.50 folds greater risk of breast cancer than vitamin D insufficient women. In current study premenopausal women with ff genotype had 2.416 folds increase risk of breast cancer as compared to premenopausal women with Ff genotype. The study concluded overall low vitamin D concentrations in Pakistani women and vitamin D deficiency may be a potential contributor of breast cancer in our population. VDR FokI SNP was found to be associated with breast cancer risk in premenopausal women whereas TaqI SNP has no significant association with breast cancer risk in Pakistani women.

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