Genetic polymorphisms in vitamin D receptor VDR/RXRA influence the likelihood of colon adenoma recurrence.
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.
Egan
Jan B
JB
Arizona Cancer Center, University of Arizona and Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona 85724-5024, USA.
Thompson
Patricia A
PA
Ashbeck
Erin L
EL
Conti
David V
DV
Duggan
David
D
Hibler
Elizabeth
E
Jurutka
Peter W
PW
Leroy
Elizabeth C
EC
Martínez
María Elena
ME
Mount
David
D
Jacobs
Elizabeth T
ET
D000236:Adenoma / Q000178:diet therapy / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017326:Clinical Trials, Phase III as Topic; D003110:Colonic Neoplasms / Q000178:diet therapy / Q000235:genetics* / Q000473:pathology; D004311:Double-Blind Method; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D016032:Randomized Controlled Trials as Topic; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D012008:Recurrence; D047490:Retinoid X Receptor alpha / Q000235:genetics* / Q000378:metabolism
D018167:Receptors, Calcitriol; D047490:Retinoid X Receptor alpha