title: Association of the ARLTS1 Cys148Arg variant with familial breast cancer risk.
abstract: Recently, ARLTS1 (ADP-ribosylation factor-like tumor suppressor gene 1) has been identified as a tumor suppressor gene, playing a major role in apoptotic signaling. The ARLTS1 Trp149Stop mutation has been shown to predispose to general familial cancer and high-risk familial breast cancer (BC), provoking the attenuation of apoptotic function. We studied the impact of the ARLTS1 Pro131Leu and Cys148Arg variants on high-risk familial and familial BC risk, investigating 482 familial BC cases (including 305 high-risk cases) and 530 control individuals. Unlike ARLTS1 Pro131Leu, Cys148Arg revealed a significant association with an increased risk of high-risk familial BC (odds ratio (OR)=1.47, 95% confidence interval (95% CI)=1.04-2.06, p=0.03) in a dose-dependent manner (ptrend=0.007). The genotype distribution of Cys148Arg in familial cases was similar, indicating significance as well (OR=1.48, 95% CI=1.10-1.99, p=0.009; ptrend=0.003). On the basis of the small number of 46 cases, we additionally showed an association between the Trp149Stop mutation and an increased risk of bilateral BC (OR=4.11, 95% CI=1.27-13.31, p=0.011).
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany. b.frank@dkfz.de
authors.forename: Bernd
authors.initials: B
authors.lastname: Frank
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.forename: Alfons
authors.initials: A
authors.lastname: Meindl
authors.forename: Barbara
authors.initials: B
authors.lastname: Wappenschmidt
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Klaes
authors.forename: Rita K
authors.initials: RK
authors.lastname: Schmutzler
authors.forename: Michael
authors.initials: M
authors.lastname: Untch
authors.forename: Peter
authors.initials: P
authors.lastname: Bugert
authors.forename: Claus R
authors.initials: CR
authors.lastname: Bartram
authors.forename: Barbara
authors.initials: B
authors.lastname: Burwinkel
mesh_terms: D020727:ADP-Ribosylation Factors / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D007839:Functional Laterality; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D010375:Pedigree; D012307:Risk Factors
chemical_list: D020727:ADP-Ribosylation Factors; C500039:ARL11 protein, human