1. ¹Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere, Tampere, Finland
2. ²Laboratory of Cancer Genetics, Institute of Medical Technology, Tampere University Hospital, Tampere, Finland
3. ³Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Helsinki, Finland
4. ⁴Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, MD, USA
5. ⁵Department of Oncology, University of Tampere, Tampere, Finland
6. ⁶Department of Oncology, Tampere University Hospital, Tampere, Finland
7. ⁷Department of Urology, Tampere University Hospital, Tampere, Finland
8. ⁸Medical School, University of Tampere, Tampere, Finland
9. ⁹Second Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland
10. ¹⁰Department of Surgery, Jyväskylä Central Hospital, Jyväskylä, Finland
11. ¹¹Department of Clinical Genetics, Helsinki University Central Hospital, Helsinki, Finland
12. ¹²Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland
13. ¹³Department of Medical Genetics, University of Helsinki, Helsinki, Finland

Correspondence: Dr P Vahteristo, Department of Medical Genetics, Biomedicum Helsinki, PO Box 63, FIN-00014 University of Helsinki, Helsinki, Finland. Tel: +358 9 1912 5600; Fax +358 9 1912 5105; E-mail: pia.vahteristo@helsinki.fi

Received 25 July 2007; Revised 5 January 2008; Accepted 5 February 2008; Published online 12 March 2008.

Abstract

Recently, a nonsense alteration Trp149Stop in the ARLTS1 gene was found more frequently in familial cancer cases versus sporadic cancer patients and healthy controls. Here, the role of Trp149Stop or any other ARLTS1 germline variant was evaluated on breast, prostate, and colorectal cancer risk. The whole gene was screened for germline alterations in 855 familial cancer patients. The five observed variants were further screened in 1169 non-familial cancer patients as well as in 809 healthy population controls. The Trp149Stop was found at low frequencies (0.5–1.2%) in all patient subgroups versus 1.6% in controls, and the mutant allele did not co-segregate with disease status in families with multiple affected individuals. The CC genotype in the Cys148Arg variant was slightly more common among both familial and sporadic breast (odds ratio (OR), 1.48; 95% confidence interval (CI), 1.16–1.87; P=0.001) and prostate cancer patients (OR, 1.50; 95% CI, 1.13–1.99; P=0.005) when compared to controls. A novel ARLTS1 variant Gly65Val was found at higher frequency among familial prostate cancer patients (8 of 164, 4.9%) than in controls (13 of 809, 1.6%; OR, 3.14; 95% CI, 1.28–7.70, P=0.016). However, after adjusting for multiple testing, none of these results were still significant. No association was found with any of the variants and colorectal cancer risk. Our results suggest that Trp149Stop is not a predisposition allele in breast, prostate, or colorectal cancer in the Finnish population, and, while the Gly65Val variant may increase familial prostate cancer risk and the Cys148Arg change may affect both breast and prostate cancer risk, the evidence is not strong in these data.