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A Journal on Internal Medicine
Indexed/Abstracted in: Current Contents/Clinical Medicine, EMBASE, PubMed/MEDLINE, Science Citation Index Expanded (SciSearch), Scopus
Impact Factor 1,236
Minerva Medica 2013 June;104(3):295-307
Evidences of dual role of vitamin D through cellular energy homeostasis and inflammation pathway in risk of cancer in obese subjects
Hossein-Nezhad A. 1, 2, Mirzaei K. 1, Keshavarz S. A. 1, Ansar H. 1, Saboori S. 1, Tootee A. 1 ✉
1 Section of Endocrinology, Nutrition, and Diabetes, Vitamin D, Skin and Bone Research Laboratory, Tehran University of Medical Sciences, Tehran, Iran;
2 Department of Medicine, Boston University Medical Center, Boston, MA, USA
Aim: The underlying molecular mechanisms of the role obesity plays in increasing the risk of cancer are not well illuminated. Several mechanisms are proposed for vitamin D as an anti-cancer agent in various malignancies which may be attributed to both its both its anti-inflammatory characteristics as well as its mediatory role in cellular energy homeostasis. This study evaluates the expression of PBMCs’ genes which are involved in cellular energy homeostasis such as VDR, PPARγ, PGC1a and UCP2. Moreover, considering the possible role of vitamin D in the inflammation mechanisms, we also aimed at measurement of some inflammatory mediators such as TNF-α, IL-1β, IL4, IL-6, IL10, IL13 and IL17 in inflammatory state in samples obtained from obese persons with and without positive family history of cancer. Moreover, to expand the study to a clinical context, we assessed the correlation of the resting metabolic rate with the evaluated gene.
Methods: A total of 274 obese women were included in the current cross-sectional study. All of participants were class I obese. By constructing a pedigree that includes 3 generations, twenty-one subjects were at increased risk because of a positive family history of colorectal cancer. Accordingly, current study’s analysis was based on positive and negative family history of colorectal cancer.
Results: The concentration of Insulin and PTH were significantly high in group with positive history of cancer. 25 (OH) vitamin D, REE/kg and REE/FFM statuses in two groups; the level of mentioned terms were lower in group with positive history of cancer compared to group with negative history of cancer. We found significantly lower REE/kg in deficiency of vitamin D and higher REE/kg in sufficiency status. Our results demonstrated significant higher concentrations of IL1β, IL17, TNFα and IL6 in group with positive history of cancer compared to group with negative history of cancer. The concentrations of IL13, IL10 and IL4 were significantly lower in group with positive history of cancer compared to group with negative history of cancer. The relative expression of VDR, PGC1αand PPARγ gene was significantly lower in group with positive history of cancer. The relative expression of UCP2 was almost significantly lesser in group with positive history of cancer also.
Conclusion: The observed mutual alteration in the levels of inflammatory markers and relative expression of important gene in energy homeostasis may be caused by vitamin D deficiency among the obese subjects with positive history of colorectal cancer.