Dysregulation of vitamin D synthesis pathway genes in colorectal cancer: A case-control study.

Abstract

BACKGROUND:

The cytochromes P450 are a superfamily of enzymes that control the synthesis of the biologically active form of vitamin D, 1,25-dihydroxyvitamin D3. These enzymes contribute to the formation of 1,25-dihydroxyvitamin D3, which starts with a 25-hydroxylation by CYP2R1 and CYP27A1 and a subsequent 1α-hydroxylation via CYP27B1.

METHODS:

By using quantitative real-time polymerase chain reaction (qRT-PCR), we analyzed the expression ratio of CYP2R1, CYP27A1 and CYP27B1 genes within the vitamin D metabolic pathway in a total of 75 colorectal cancer (CRC) tissues compared to the adjacent tissues. Furthermore, we evaluated the association of CYP27B1 rs4646536 and CYP2R1 rs12794714 and rs10766196 polymorphisms with CRC risk in a total of 490 subjects, including 245 CRC patients and 245 non-cancer controls. The genotyping was performed using tetra-primer amplification refractory mutation system polymerase chain reaction (TP-ARMS-PCR) method.

RESULTS:

The results indicated 2.3 and 2.7 upregulation of CYP2R1 and CYP27B1 genes in colorectal cancer tissues compared to the adjacent tissues, respectively. Rs12794714 AG genotype increased the risk of CRC (P = .03). Furthermore, a significant association was observed under the dominant inheritance model (P = .039).

CONCLUSION:

CYP2R1 and CYP27B1 genes were over-expressed in CRC samples compared to the adjacent control tissues. Furthermore, CYP2R1 rs12794714 variant was associated with the risk of CRC in the studied samples. CYP2R1 rs10766196 and CYP27B1 rs4646536 are not responsible for CYP2R1 and CYP27B1 genes expression alteration, respectively, but CYP2R1 rs12794714 polymorphism may be the reason of CYP2R1 upregulation and increased the risk of CRC.

• Authors: Hossein Sadeghi, Zeeba Kamaliyan, Roohollah Mohseni, Unes Sahebi, Ehsan Nazemalhosseini-Mojarad, Naser Aghaei, Mohammad Reza Zali, Hamid Asadzadeh Aghdaei, Reza Mirfakhraie, Arfa Moshiri
• Journal: Journal of clinical laboratory analysis (J Clin Lab Anal) Vol. 35 Issue 2 Pg. e23617 (Feb 2021) ISSN: 1098-2825 [Electronic] United States
• PMID: 33058307 (Publication Type: Journal Article)
• Copyright: © 2020 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.

Chemical References

• Vitamin D
• Cytochrome P450 Family 2
• CYP2R1 protein, human
• CYP27A1 protein, human
• Cholestanetriol 26-Monooxygenase
• 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
• CYP27B1 protein, human

Topics

• 25-Hydroxyvitamin D3 1-alpha-Hydroxylase (genetics)
• Aged
• Case-Control Studies
• Cholestanetriol 26-Monooxygenase (genetics)
• Colorectal Neoplasms (genetics, metabolism, pathology)
• Cytochrome P450 Family 2 (genetics)
• Female
• Gene Expression Regulation, Neoplastic
• Gene Frequency
• Humans
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Vitamin D (biosynthesis, genetics)