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Vitamin D Related Genes, CYP24A1 and CYP27B1, and Colon Cancer Risk
Genetic association studies investigating the role of vitamin D in colon cancer have primarily focused on the vitamin D receptor ( VDR ), with limited data available for other genes in the vitamin D pathway, including vitamin D activating enzyme 1-α hydroxylase ( CYP27B1 ) and vitamin D deactivating...
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Published in: | Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2009-09, Vol.18 (9), p.2540-2548 |
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Main Authors: | , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
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Online Access: | Get full text |
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Summary: | Genetic association studies investigating the role of vitamin D in colon cancer have primarily focused on the vitamin D receptor
( VDR ), with limited data available for other genes in the vitamin D pathway, including vitamin D activating enzyme 1-α hydroxylase
( CYP27B1 ) and vitamin D deactivating enzyme 24-α hydroxylase ( CYP24A1 ). We evaluated whether 12 tagging single nucleotide polymorphisms (SNP) in CYP24A1 , identified by resequencing the gene in 32 Caucasian samples, and 1 SNP in CYP27B1 were associated with colon cancer risk. In addition, we evaluated whether these two genes modify associations between colon
cancer on the one hand and total vitamin D intake and UV-weighted sun exposure on the other, as well as other variants in
VDR. Unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for the association
between polymorphisms and haplotypes in CYP27B1 and CYP24A1 in a multicenter population-based case-control study of 1,600 cases and 1,949 controls. The CYP24A1 polymorphism IVS4-66T > G showed a statistically significant association with risk of colon cancer overall, particularly for proximal colon cancer.
When stratified by anatomic site, we also found statistically significant associations for three CYP24A1 polymorphisms with risk of distal colon cancer ( IVS4 + 1653C > T : OR for CT/TT versus CC, 0.81; 95% CI, 0.68-0.96; IVS9 + 198T > C : OR for CC versus TT, 1.33; 95% CI, 1.03-1.73; and within whites only: + 4125bp 3′ of STPC > G : OR for GG versus CC, 1.44; 95% CI, 1-2.05). In addition, a possible interaction between CYP27B1 and UV-weighted sun exposure with proximal colon cancer was observed. As this is the first study to evaluate these genes
in relation to colon cancer, additional studies are needed to confirm these results. (Cancer Epidemiol Biomarkers Prev 2009;18(9):2540–8) |
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ISSN: | 1055-9965 1538-7755 |
DOI: | 10.1158/1055-9965.EPI-09-0228 |