Study of genetic polymorphism of vitamin D receptor BsmI, ApaI and CYP27B1 and CYP24A1 genes and their relationship to serum levels of vitamin D and colorectal cancer susceptibility

• Grant number: 11/05979-0
• Support Opportunities: Regular Research Grants
• Start date: January 01, 2012
• End date: June 30, 2014
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Nora Manoukian Forones
• Grantee: Nora Manoukian Forones
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Tiago Donizetti da Silva ; Verônica Marques Vidigal

Abstract

The INCA estimates about 13,310 new cases of colorectal cancer in men and 14,800 women in the year 2011. Studies have shown that high intake of red meat and highly refined grains increases the incidence of colorectal cancer, while ingestion of legumes, fruits and meat from poultry and fish reduce the risk of disease. There is also a possible role of calcium and vitamin D as components of a protective effect on cancer of the colon and rectum. Vitamin D in its most active form (1,25-dihydroxyvitamin D) is described as a regulator of proliferation and differentiation of human cancer cells, and skin exposure to sunlight to obtain the main route for most people (more than 90%). After the synthesis initiated by exposing the skin to sunlight (from the action of ultraviolet light) to 1.25 (OH) 2 vitamin D binds to specific DNA sequences in the promoter regions of genes that are activated by vitamin D and variations (polymorphisms) of the vitamin D receptor actions interfere with the bowel. This vitamin D receptor (VDR) are proteins whose function, mediate the effects of vitamin D in bone and mineral metabolism, regulate growth and differentiation of target tissues and act as a modulator of the immune system. Objectives: To determine the frequency of polymorphisms BsmI, ApaI of VDR and CYP24A1 and CYP27B1 genes in a Brazilian population of São Paulo region. To correlate the genotype frequency of these polymorphisms to the risk of colorectal cancer and serum levels of vitamin D. Methods: 150 patients will be screened for colorectal cancer in the cancer ward of the Department of Clinical Gastroenterology, UNIFESP-EPM, and 300 individuals without cancer who constitute the control group. All will undergo an interview and collection of peripheral blood for genomic DNA extraction and assessment of serum vitamin D (through the technique of HPLC). The presence of polymorphisms will be investigated using the technique of polymerase chain reaction (PCR) and genotyping by RFLP and sequencing technique. Samples will be analyzed by a running agarose gel electrophoresis and revealed by ethidium bromide. (AU)