ARLTS1 germline variants and the risk for breast, prostate, and colorectal cancer
| Autor: | Heli Nevanlinna, Jukka-Pekka Mecklin, Pia Vahteristo, Kaija Holli, Kirsi Syrjäkoski, Peter Lipman, Heikki Järvinen, Sanna Siltanen, Carl Blomqvist, Teuvo L.J. Tammela, Rainer Fagerholm, Joan E. Bailey-Wilson, Lauri A. Aaltonen, Jacob Mallott, Johanna Schleutker, Tarja Ikonen, Kristiina Aittomäki |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
Oncology medicine.medical_specialty Genotype Colorectal cancer DNA Mutational Analysis Breast Neoplasms Polymorphism Single Nucleotide Article Familial prostate cancer 03 medical and health sciences Prostate cancer 0302 clinical medicine Breast cancer Risk Factors Internal medicine Odds Ratio Genetics medicine Humans Genetic Predisposition to Disease Risk factor Germ-Line Mutation Genetics (clinical) 030304 developmental biology 0303 health sciences ADP-Ribosylation Factors business.industry Genetic Variation Prostatic Neoplasms Cancer Odds ratio medicine.disease Pedigree 3. Good health Endocrinology Case-Control Studies 030220 oncology & carcinogenesis Female Breast disease Colorectal Neoplasms business |
| Zdroj: | European Journal of Human Genetics. 16:983-991 |
| ISSN: | 1476-5438 1018-4813 |
| DOI: | 10.1038/ejhg.2008.43 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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