Genetic variation in the retinoid X receptor and calcium-sensing receptor and risk of colorectal cancer in the Colon Cancer Family Registry

Elizabeth T Jacobs, Maria E. Martínez, Peter T. Campbell, David V. Conti, David Duggan, Jane C. Figueiredo, Robert W. Haile, Elizabeth C. LeRoy, Jenny N. Poynter, Patricia A. Thompson, John A. Baron

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Genetic variants in the calcium/vitamin D metabolic pathway may be related to risk for colorectal cancer. While several investigations of vitamin D receptor (VDR) polymorphisms and colorectal cancer have been conducted, no studies to date have evaluated the association of genetic variation in the heterodimer partner for VDR, the retinoid X receptor (RXR). Another important gene in this pathway is the calcium-sensing receptor (CASR). Employing a discordant-sibship case-control design, we examined the association between single nucleotide polymorphisms (SNPs) in RXRA and CASR and risk for colorectal cancer overall and by colorectal subsite and microsatellite instability (MSI) status using data from the Colon Cancer Family Registry. No gene-level relationships between RXRA or CASR and colorectal cancer overall were observed. However, for RXRA SNP rs7861779, a high-interest SNP selected for study apriori, there was a statistically significantly increased risk for proximal colorectal cancer among those with at least one A allele [odds ratio (OR)=1.42; 95% confidence interval (CI)=1.03-1.97]. Another selected RXRA SNP, rs12004589, was significantly associated with risk of MSI-high cancers (OR=2.27; 95% CI=1.13-4.56). Additionally, CASR SNP rs1801726 was significantly associated with a reduced risk for rectal cancer (OR=0.53; 95% CI=0.29-0.96). These results provide support that RXRA SNPs rs7861779 and rs12004589 and CASR SNP rs1801726 may be important markers for colorectal neoplasia. Further work is needed to elucidate their role in the carcinogenic pathway.

Original languageEnglish (US)
Pages (from-to)1412-1416
Number of pages5
JournalCarcinogenesis
Volume31
Issue number8
DOIs
StatePublished - Jun 17 2010

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Retinoid X Receptors
Calcium-Sensing Receptors
Colonic Neoplasms
Single Nucleotide Polymorphism
Registries
Colorectal Neoplasms
Microsatellite Instability
Calcitriol Receptors
Odds Ratio
Confidence Intervals
Rectal Neoplasms
Metabolic Networks and Pathways
Vitamin D
Genes
Neoplasms
Alleles
Calcium

ASJC Scopus subject areas

  • Cancer Research

Cite this

Genetic variation in the retinoid X receptor and calcium-sensing receptor and risk of colorectal cancer in the Colon Cancer Family Registry. / Jacobs, Elizabeth T; Martínez, Maria E.; Campbell, Peter T.; Conti, David V.; Duggan, David; Figueiredo, Jane C.; Haile, Robert W.; LeRoy, Elizabeth C.; Poynter, Jenny N.; Thompson, Patricia A.; Baron, John A.

In: Carcinogenesis, Vol. 31, No. 8, 17.06.2010, p. 1412-1416.

Research output: Contribution to journalArticle

Jacobs, ET, Martínez, ME, Campbell, PT, Conti, DV, Duggan, D, Figueiredo, JC, Haile, RW, LeRoy, EC, Poynter, JN, Thompson, PA & Baron, JA 2010, 'Genetic variation in the retinoid X receptor and calcium-sensing receptor and risk of colorectal cancer in the Colon Cancer Family Registry', Carcinogenesis, vol. 31, no. 8, pp. 1412-1416. https://doi.org/10.1093/carcin/bgq127
Jacobs, Elizabeth T ; Martínez, Maria E. ; Campbell, Peter T. ; Conti, David V. ; Duggan, David ; Figueiredo, Jane C. ; Haile, Robert W. ; LeRoy, Elizabeth C. ; Poynter, Jenny N. ; Thompson, Patricia A. ; Baron, John A. / Genetic variation in the retinoid X receptor and calcium-sensing receptor and risk of colorectal cancer in the Colon Cancer Family Registry. In: Carcinogenesis. 2010 ; Vol. 31, No. 8. pp. 1412-1416.
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AU - Duggan, David

AU - Figueiredo, Jane C.

AU - Haile, Robert W.

AU - LeRoy, Elizabeth C.

AU - Poynter, Jenny N.

AU - Thompson, Patricia A.

AU - Baron, John A.

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