Association of the ARLTS1 Cys148Arg variant with familial breast cancer risk |
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Authors: | Frank Bernd Hemminki Kari Meindl Alfons Wappenschmidt Barbara Klaes Rüdiger Schmutzler Rita K Untch Michael Bugert Peter Bartram Claus R Burwinkel Barbara |
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Affiliation: | Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany. b.frank@dkfz.de |
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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). |
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Keywords: | familial breast cancer risk ARLTS1 tumor suppressor gene polymorphism |
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