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

Jan B. Egan, Patricia A. Thompson, Erin L. Ashbeck, David V. Conti, David Duggan, Elizabeth Hibler, Peter Jurutka, Elizabeth C. LeRoy, María Elena Martínez, David Mount, Elizabeth T. Jacobs

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1496-1504
Number of pages9
JournalCancer Research
Volume70
Issue number4
DOIs
StatePublished - Feb 15 2010

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Calcitriol Receptors
Genetic Polymorphisms
Adenoma
Colon
Single Nucleotide Polymorphism
Recurrence
Haplotypes
Neoplasms
Vitamin D
Confidence Intervals
Retinoid X Receptors
Genes
Colorectal Neoplasms
Odds Ratio
Population

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Egan, J. B., Thompson, P. A., Ashbeck, E. L., Conti, D. V., Duggan, D., Hibler, E., ... Jacobs, E. T. (2010). Genetic polymorphisms in vitamin D receptor VDR/RXRA influence the likelihood of colon adenoma recurrence. Cancer Research, 70(4), 1496-1504. https://doi.org/10.1158/0008-5472.CAN-09-3264

Genetic polymorphisms in vitamin D receptor VDR/RXRA influence the likelihood of colon adenoma recurrence. / Egan, Jan B.; Thompson, Patricia A.; Ashbeck, Erin L.; Conti, David V.; Duggan, David; Hibler, Elizabeth; Jurutka, Peter; LeRoy, Elizabeth C.; Martínez, María Elena; Mount, David; Jacobs, Elizabeth T.

In: Cancer Research, Vol. 70, No. 4, 15.02.2010, p. 1496-1504.

Research output: Contribution to journalArticle

Egan, JB, Thompson, PA, Ashbeck, EL, Conti, DV, Duggan, D, Hibler, E, Jurutka, P, LeRoy, EC, Martínez, ME, Mount, D & Jacobs, ET 2010, 'Genetic polymorphisms in vitamin D receptor VDR/RXRA influence the likelihood of colon adenoma recurrence', Cancer Research, vol. 70, no. 4, pp. 1496-1504. https://doi.org/10.1158/0008-5472.CAN-09-3264
Egan, Jan B. ; Thompson, Patricia A. ; Ashbeck, Erin L. ; Conti, David V. ; Duggan, David ; Hibler, Elizabeth ; Jurutka, Peter ; LeRoy, Elizabeth C. ; Martínez, María Elena ; Mount, David ; Jacobs, Elizabeth T. / Genetic polymorphisms in vitamin D receptor VDR/RXRA influence the likelihood of colon adenoma recurrence. In: Cancer Research. 2010 ; Vol. 70, No. 4. pp. 1496-1504.
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abstract = "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.",
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AU - Ashbeck, Erin L.

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AU - Duggan, David

AU - Hibler, Elizabeth

AU - Jurutka, Peter

AU - LeRoy, Elizabeth C.

AU - Martínez, María Elena

AU - Mount, David

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