title: Vitamin D receptor polymorphisms or serum levels as key drivers of breast cancer development? The question of the vitamin D pathway.
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.
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Dino
authors.initials: D
authors.lastname: Amadori
authors.affiliation: Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Serra
authors.affiliation: Department of Oncology, Bugando Medical Center, Mwanza, Tanzania, Africa.
authors.forename: Nestory
authors.initials: N
authors.lastname: Masalu
authors.affiliation: Department of Oncology, Bugando Medical Center, Mwanza, Tanzania, Africa.
authors.forename: Akwilina
authors.initials: A
authors.lastname: Pangan
authors.affiliation: Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Scarpi
authors.affiliation: Department of Oncology, Bugando Medical Center, Mwanza, Tanzania, Africa.
authors.forename: Aloyce Maria
authors.initials: AM
authors.lastname: Bugingo
authors.affiliation: Department of Oncology, Bugando Medical Center, Mwanza, Tanzania, Africa.
authors.forename: Deogratias
authors.initials: D
authors.lastname: Katabalo
authors.affiliation: Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Toni
authors.initials: T
authors.lastname: Ibrahim
authors.affiliation: Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bongiovanni
authors.affiliation: Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Miserocchi
authors.affiliation: Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Spadazzi
authors.affiliation: Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Liverani
authors.affiliation: Healthcare Administration, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Turri
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Tedaldi
authors.affiliation: Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Mercatali
mesh_terms: D000328:Adult; D000483:Alleles; D044383:Black People / Q000235:genetics; D001943:Breast Neoplasms / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007558:Italy; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D018167:Receptors, Calcitriol / Q000097:blood / Q000235:genetics*; D012307:Risk Factors; D015398:Signal Transduction; D013636:Tanzania; D014807:Vitamin D / Q000097:blood; D014809:Vitamin D-Binding Protein / Q000097:blood; D044465:White People / Q000235:genetics
chemical_list: D018167:Receptors, Calcitriol; C579457:VDR protein, human; D014809:Vitamin D-Binding Protein; D014807:Vitamin D
keywords: 25(OH)D; Africans; caucasians; vitamin D binding protein; vitamin D pathway