Frank Bernd, Hemminki Kari, Meindl Alfons, Wappenschmidt Barbara, Klaes Rüdiger, Schmutzler Rita K, Untch Michael, Bugert Peter, Bartram Claus R, Burwinkel Barbara
Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
Int J Cancer. 2006 May 15;118(10):2505-8. doi: 10.1002/ijc.21687.
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).
最近，ARLTS1（ADP核糖基化因子样肿瘤抑制基因1）已被鉴定为一种肿瘤抑制基因，在凋亡信号传导中起主要作用。ARLTS1基因的Trp149Stop突变已被证明易患一般家族性癌症和高危家族性乳腺癌（BC），导致凋亡功能减弱。我们研究了ARLTS1基因Pro131Leu和Cys148Arg变异对高危家族性和家族性BC风险的影响，调查了482例家族性BC病例（包括305例高危病例）和530名对照个体。与ARLTS1基因Pro131Leu不同，Cys148Arg与高危家族性BC风险增加呈显著关联（优势比（OR）=1.47，95%置信区间（95%CI）=1.04-2.06，p=0.03），呈剂量依赖性（趋势p=0.007）。家族性病例中Cys148Arg的基因型分布相似，也具有显著性（OR=1.48，95%CI=1.10-1.99，p=0.009；趋势p=0.003）。基于46例的少量样本，我们还发现Trp149Stop突变与双侧BC风险增加之间存在关联（OR=4.11，95%CI=1.27-13.31，p=0.011）。
