Vitamin D receptor polymorphisms or serum levels as key drivers of breast cancer development? The question of the vitamin D pathway

// Dino Amadori 1 , Patrizia Serra 2 , Nestory Masalu 3 , Akwilina Pangan 3 , Emanuela Scarpi 2 , Aloyce Maria Bugingo 3 , Deogratias Katabalo 3 , Toni Ibrahim 4 , Alberto Bongiovanni 4 , Giacomo Miserocchi 4 , Chiara Spadazzi 4 , Chiara Liverani 4 , Valentina Turri 5 , Rosanna Tedaldi 1 , Laura Mercatali 4 1 Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy 2 Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy 3 Department of Oncology, Bugando Medical Center, Mwanza, Tanzania, Africa 4 Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy 5 Healthcare Administration, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy Correspondence to: Dino Amadori, email: dino.amadori@irst.emr.it Keywords: Africans, caucasians, 25(OH)D, vitamin D pathway, vitamin D binding protein Received: September 27, 2016      Accepted: December 15, 2016      Published: January 04, 2017 ABSTRACT As total vitamin D levels are often lower in black than in white Americans, the former are frequently classified as vitamin D-deficient. To fully understand African vitamin D (25(OH)D) status, other factors should be considered, e.g. vitamin D blood carrier, vitamin D-binding protein (DBP), vitamin D receptor ( VDR ) and DBP polymorphisms. A prospective study on an indigenous black Tanzanian and a Caucasian Italian population was performed on 50 healthy donors from both populations and 35 Caucasian and 18 African breast cancer patients. 25(OH)D and DBP serum levels were analyzed by ELISA. A1012G, Cdx2 and Fok1 VDR polymorphisms and DBP polymorphisms rs4588 and rs7041 were genotyped by real-time PCR. Vitamin D and DBP levels were lower in healthy African donors than in Caucasians. Africans had a significantly higher frequency of AA and CC for Cdx2 and Fok1 polymorphisms, respectively. These allelic variants were related to a higher transcription of VDR gene and a higher activity of VDR receptor. With regard to polymorphism distribution, Africans showed innate higher levels and activity of VDR. We conclude that a strengthening of the vitamin D pathway could have a protective role against the development of breast cancer in the African population.