TY - JOUR
T1 - Genetic polymorphisms in vitamin D receptor VDR/RXRA influence the likelihood of colon adenoma recurrence
AU - Egan, Jan B.
AU - Thompson, Patricia A.
AU - Ashbeck, Erin L.
AU - Conti, David V.
AU - Duggan, David
AU - Hibler, Elizabeth
AU - Jurutka, Peter
AU - LeRoy, Elizabeth C.
AU - Martínez, María Elena
AU - Mount, David
AU - Jacobs, Elizabeth T.
PY - 2010/2/15
Y1 - 2010/2/15
N2 - Low circulating levels of vitamin D affect colorectal cancer risk. The biological actions of the hormonal form of vitamin D, 1,25(OH)2D 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 ∼30% reduction in odds of metachronous neoplasia arising in the proximal colon among carriers of specific haplotypes, which was strongest (ORproximal, 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.
AB - Low circulating levels of vitamin D affect colorectal cancer risk. The biological actions of the hormonal form of vitamin D, 1,25(OH)2D 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 ∼30% reduction in odds of metachronous neoplasia arising in the proximal colon among carriers of specific haplotypes, which was strongest (ORproximal, 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.
UR - http://www.scopus.com/inward/record.url?scp=76749095410&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=76749095410&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-09-3264
DO - 10.1158/0008-5472.CAN-09-3264
M3 - Article
C2 - 20145122
AN - SCOPUS:76749095410
SN - 0008-5472
VL - 70
SP - 1496
EP - 1504
JO - Cancer Research
JF - Cancer Research
IS - 4
ER -