Association of the ARLTS1 Cys148Arg variant with familial breast cancer risk

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factors / genetics*
  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / etiology
  • Breast Neoplasms / genetics*
  • Case-Control Studies
  • DNA Mutational Analysis
  • Female
  • Functional Laterality
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genotype
  • Humans
  • Middle Aged
  • Odds Ratio
  • Pedigree
  • Risk Factors


  • ADP-Ribosylation Factors
  • ARL11 protein, human