Premium
Association of the ARLTS1 Cys148Arg variant with familial breast cancer risk
Author(s) -
Frank Bernd,
Hemminki Kari,
Meindl Alfons,
Wappenschmidt Barbara,
Klaes Rüdiger,
Schmutzler Rita K.,
Untch Michael,
Bugert Peter,
Bartram Claus R.,
Burwinkel Barbara
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21687
Subject(s) - odds ratio , breast cancer , medicine , oncology , confidence interval , genotype , family aggregation , risk factor , case control study , mutation , tumor suppressor gene , allele , cancer , genetics , gene , biology , carcinogenesis , disease
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 ( p trend = 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; p trend = 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). © 2005 Wiley‐Liss, Inc.