Genetic polymorphisms in vitamin D receptor VDR/RXRA influence the likelihood of colon adenoma recurrence.

Egan JB, Thompson PA, Ashbeck EL, Conti DV, Duggan D, Hibler E, Jurutka PW, Leroy EC, Martínez ME, Mount D, Jacobs ET
Cancer Res. 2010 70 (4): 1496-504

PMID: 20145122 · PMCID: PMC3019606 · DOI:10.1158/0008-5472.CAN-09-3264

Low circulating levels of vitamin D affect colorectal cancer risk. The biological actions of the hormonal form of vitamin D, 1,25(OH)(2)D(3), are mediated by the vitamin D receptor (VDR), which heterodimerizes with retinoid X receptors (RXR). Using a single nucleotide polymorphism (SNP) tagging approach, we assessed the association between genetic variations in RXRA and VDR and odds of recurrent (metachronous) colorectal neoplasia in a pooled population of two studies. A total of 32 tag SNPs in RXRA and 42 in VDR were analyzed in 1,439 participants. A gene-level association was observed for RXRA and any (P = 0.04) or proximal (P = 0.03) metachronous neoplasia. No gene-level associations were observed for VDR, nor was any single SNP in VDR related to any metachronous adenoma after correction for multiple comparisons. In contrast, the association between RXRA SNP rs7861779 and proximal metachronous neoplasia was of borderline statistical significance [odds ratio (OR), 0.68; 95% confidence interval (95% CI), 0.53-0.86; unadjusted P = 0.001; adjusted P = 0.06], including when observed independently in each individual study. Haplotypes within linkage blocks of RXRA support an approximately 30% reduction in odds of metachronous neoplasia arising in the proximal colon among carriers of specific haplotypes, which was strongest (OR(proximal), 0.67; 95% CI, 0.52-0.86) for carriers of a CGGGCA haplotype (rs1805352, rs3132297, rs3132296, rs3118529, rs3118536, and rs7861779). Our results indicate that allelic variation in RXRA affects metachronous colorectal neoplasia, perhaps of particular importance in the development of proximal lesions.

MeSH Terms (17)

Adenoma Adult Aged Aged, 80 and over Clinical Trials, Phase III as Topic Colonic Neoplasms Double-Blind Method Female Genetic Predisposition to Disease Humans Male Middle Aged Polymorphism, Single Nucleotide Randomized Controlled Trials as Topic Receptors, Calcitriol Recurrence Retinoid X Receptor alpha

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