title: Polymorphisms of the dopamine receptor gene DRD2 and colorectal cancer risk.
abstract: 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.
authors: International Agency for Research on Cancer, Lyon, France.
authors: Federica
authors: F
authors: Gemignani
authors: Stefano
authors: S
authors: Landi
authors: Victor
authors: V
authors: Moreno
authors: Lydie
authors: L
authors: Gioia-Patricola
authors: Amélie
authors: A
authors: Chabrier
authors: Elisabet
authors: E
authors: Guino
authors: Matilde
authors: M
authors: Navarro
authors: Maria
authors: M
authors: Cambray
authors: Gabriel
authors: G
authors: Capellà
authors: Federico
authors: F
authors: Canzian
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017448:Receptors, Dopamine D2 / Q000235:genetics*
chemical_list: D017448:Receptors, Dopamine D2