Association of the ARLTS1 Cys148Arg variant with sporadic and familial colorectal cancer

• Published in: Carcinogenesis (New York) 2007-08, Vol.28 (8), p.1687-1691
• Main Authors: Castellví-Bel, Sergi, Castells, Antoni, de Cid, Rafael, Muñoz, Jenifer, Balaguer, Francesc, Gonzalo, Victoria, Ruiz-Ponte, Clara, Andreu, Montserrat, Llor, Xavier, Jover, Rodrigo, Bessa, Xavier, Xicola, Rosa M., Pons, Elisenda, Alenda, Cristina, Payá, Artemio, Carracedo, Angel, Piqué, Josep M.
• Format: Article
• Language: English
• Subjects: ADP-Ribosylation Factors - genetics; Amino Acid Substitution - genetics; Arginine - genetics; Base Sequence; Case-Control Studies; Colorectal cancer; Colorectal Neoplasms - epidemiology; Colorectal Neoplasms - genetics; Cysteine - genetics; Genetic Predisposition to Disease; Genetic Variation; Humans; Incidence; Middle Aged; Molecular Sequence Data; Risk Factors; Spain - epidemiology
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgm098

ARLTS1 was recently identified in chromosome 13q14 as a tumor suppressor gene of the ADP-ribosylation factor family with pro-apoptotic characteristics. Additionally, one of its genetic variants (W149X) was hypothesized to be a polymorphism associated with familial cancer. We performed a large case–control association study within the EPICOLON project aimed at evaluating the sporadic and familial colorectal cancer (CRC) risk associated with ARLTS1 genetic variants. Whereas P131L and W149X did not seem to affect CRC risk, C148R did show, for the first time in CRC, statistically significant differences between cases and controls [odds ratio (OR) = 1.45, 95% confidence interval (95% CI) = 1.13–1.86, P = 0.003], sporadic cases and controls (OR = 1.59, 95% CI = 1.13–2.23, P = 0.007) and familial cases and controls (OR = 1.55, 95% CI = 1.10–2.19, P = 0.01) in agreement with a hypothetical moderate increase of the cancer risk linked to the C148R ARLTS1 variant, both in sporadic and familial CRC cases.