TY - JOUR
T1 - Polymorphisms of the dopamine receptor gene DRD2 and colorectal cancer risk
AU - Gemignani, Federica
AU - Landi, Stefano
AU - Moreno, Victor
AU - Gioia-Patricola, Lydie
AU - Chabrier, Amélie
AU - Guino, Elisabet
AU - Navarro, Matilde
AU - Cambray, Maria
AU - Capellà, Gabriel
AU - Canzian, Federico
AU - Marti-Ragué, Joan
AU - De Oca, Javier
AU - Osorio, Alfonso
AU - Del Rio, Carlos
AU - Biondo, Sebastiano
AU - Badosa, Josep M.
AU - Vilardell, Felip
AU - Lloveras, Belen
AU - Novell, Valeri
AU - Pareja, Laura
AU - Pontes, Caridad
AU - Peinado, Miguel A.
PY - 2005/7/1
Y1 - 2005/7/1
N2 - Sporadic colorectal cancer is considered a multifactorial disease in which multiple exposures interact with the individual genetic background resulting in risk modulation. Recent experimental data suggest a role of dopamine and dopamine receptors in the control of proliferation of the cells of colon and gastrointestinal tract. To investigate whether polymorphisms within dopamine receptors genes could have a role in modulating the risk of sporadic colorectal cancer, we did a case-control association study and genotyped 370 cases and 327 controls for seven single-nucleotide polymorphisms (SNP) of DRD2 (-141Cdel, 957T>C, TaqIB, TaqIA, 1412A>G, S311C, and 3208G>T) by a microarray-based technique. Three SNPs within DRD2 were associated with colorectal cancer, with a maximum odds ratio of 2.28 (95% confidence interval, 1.38-3.76) for carriers of the functional SNP -141Cdel. The haplotype which includes -141Cdel, together with the variants 957C and 1412G, shows an odds ratio of 2.86 (95% confidence interval, 1.58-5.18), as compared with the most frequent haplotype. The SNPs within DRD2 associated with colorectal cancer are known to be related to reduced levels of D2 dopamine receptor. Thus, our data point to a possible role of dopamine receptor DRD2 in modulating the risk of colorectal cancer. Future studies on dopamine receptor-mediated signal transduction may provide new insight into the mechanisms of colorectal cancer and suggest new therapeutic strategies. Copyright © 2005 American Association for Cancer Research.
AB - Sporadic colorectal cancer is considered a multifactorial disease in which multiple exposures interact with the individual genetic background resulting in risk modulation. Recent experimental data suggest a role of dopamine and dopamine receptors in the control of proliferation of the cells of colon and gastrointestinal tract. To investigate whether polymorphisms within dopamine receptors genes could have a role in modulating the risk of sporadic colorectal cancer, we did a case-control association study and genotyped 370 cases and 327 controls for seven single-nucleotide polymorphisms (SNP) of DRD2 (-141Cdel, 957T>C, TaqIB, TaqIA, 1412A>G, S311C, and 3208G>T) by a microarray-based technique. Three SNPs within DRD2 were associated with colorectal cancer, with a maximum odds ratio of 2.28 (95% confidence interval, 1.38-3.76) for carriers of the functional SNP -141Cdel. The haplotype which includes -141Cdel, together with the variants 957C and 1412G, shows an odds ratio of 2.86 (95% confidence interval, 1.58-5.18), as compared with the most frequent haplotype. The SNPs within DRD2 associated with colorectal cancer are known to be related to reduced levels of D2 dopamine receptor. Thus, our data point to a possible role of dopamine receptor DRD2 in modulating the risk of colorectal cancer. Future studies on dopamine receptor-mediated signal transduction may provide new insight into the mechanisms of colorectal cancer and suggest new therapeutic strategies. Copyright © 2005 American Association for Cancer Research.
U2 - https://doi.org/10.1158/1055-9965.EPI-05-0057
DO - https://doi.org/10.1158/1055-9965.EPI-05-0057
M3 - Article
VL - 14
SP - 1633
EP - 1638
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
SN - 1055-9965
ER -