ARLTS1 germline variants and the risk for breast, prostate, and colorectal cancer

Sanna Siltanen, Kirsi Syrjäkoski, Rainer Fagerholm, Tarja Ikonen, Peter Lipman, Jacob Mallot, Kaija Holli, Teuvo L. J Tammela, Heikki J Järvinen, Jukka-Pekka Mecklin, Kristiina Aittomäki, Carl Blomqvist, Joan E Bailey-Wilson, Heli Nevanlinna, Lauri A Aaltonen, Johanna Schleutker, Pia Vahteristo

    Research output: Contribution to journalArticleScientificpeer-review

    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."
    Original languageEnglish
    JournalEuropean Journal of Human Genetics
    Volume16
    Issue number8
    Pages (from-to)983-991
    Number of pages9
    ISSN1018-4813
    DOIs
    Publication statusPublished - 2008
    MoE publication typeA1 Journal article-refereed

    Fields of Science

    • 311 Basic medicine
    • Obstetrics and gynecology

    Cite this

    Siltanen, Sanna ; Syrjäkoski, Kirsi ; Fagerholm, Rainer ; Ikonen, Tarja ; Lipman, Peter ; Mallot, Jacob ; Holli, Kaija ; Tammela, Teuvo L. J ; Järvinen, Heikki J ; Mecklin, Jukka-Pekka ; Aittomäki, Kristiina ; Blomqvist, Carl ; Bailey-Wilson, Joan E ; Nevanlinna, Heli ; Aaltonen, Lauri A ; Schleutker, Johanna ; Vahteristo, Pia. / ARLTS1 germline variants and the risk for breast, prostate, and colorectal cancer. In: European Journal of Human Genetics. 2008 ; Vol. 16, No. 8. pp. 983-991.
    @article{2938524b470041c780efb19707484957,
    title = "ARLTS1 germline variants and the risk for breast, prostate, and colorectal cancer",
    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.{"}",
    keywords = "311 Basic medicine, Obstetrics and gynecology",
    author = "Sanna Siltanen and Kirsi Syrj{\"a}koski and Rainer Fagerholm and Tarja Ikonen and Peter Lipman and Jacob Mallot and Kaija Holli and Tammela, {Teuvo L. J} and J{\"a}rvinen, {Heikki J} and Jukka-Pekka Mecklin and Kristiina Aittom{\"a}ki and Carl Blomqvist and Bailey-Wilson, {Joan E} and Heli Nevanlinna and Aaltonen, {Lauri A} and Johanna Schleutker and Pia Vahteristo",
    year = "2008",
    doi = "10.1038/ejhg.2008.43",
    language = "English",
    volume = "16",
    pages = "983--991",
    journal = "European Journal of Human Genetics",
    issn = "1018-4813",
    publisher = "Nature Publishing Group",
    number = "8",

    }

    Siltanen, S, Syrjäkoski, K, Fagerholm, R, Ikonen, T, Lipman, P, Mallot, J, Holli, K, Tammela, TLJ, Järvinen, HJ, Mecklin, J-P, Aittomäki, K, Blomqvist, C, Bailey-Wilson, JE, Nevanlinna, H, Aaltonen, LA, Schleutker, J & Vahteristo, P 2008, 'ARLTS1 germline variants and the risk for breast, prostate, and colorectal cancer', European Journal of Human Genetics, vol. 16, no. 8, pp. 983-991. https://doi.org/10.1038/ejhg.2008.43

    ARLTS1 germline variants and the risk for breast, prostate, and colorectal cancer. / Siltanen, Sanna; Syrjäkoski, Kirsi; Fagerholm, Rainer; Ikonen, Tarja; Lipman, Peter; Mallot, Jacob; Holli, Kaija; Tammela, Teuvo L. J; Järvinen, Heikki J; Mecklin, Jukka-Pekka; Aittomäki, Kristiina; Blomqvist, Carl; Bailey-Wilson, Joan E; Nevanlinna, Heli; Aaltonen, Lauri A; Schleutker, Johanna; Vahteristo, Pia.

    In: European Journal of Human Genetics, Vol. 16, No. 8, 2008, p. 983-991.

    Research output: Contribution to journalArticleScientificpeer-review

    TY - JOUR

    T1 - ARLTS1 germline variants and the risk for breast, prostate, and colorectal cancer

    AU - Siltanen, Sanna

    AU - Syrjäkoski, Kirsi

    AU - Fagerholm, Rainer

    AU - Ikonen, Tarja

    AU - Lipman, Peter

    AU - Mallot, Jacob

    AU - Holli, Kaija

    AU - Tammela, Teuvo L. J

    AU - Järvinen, Heikki J

    AU - Mecklin, Jukka-Pekka

    AU - Aittomäki, Kristiina

    AU - Blomqvist, Carl

    AU - Bailey-Wilson, Joan E

    AU - Nevanlinna, Heli

    AU - Aaltonen, Lauri A

    AU - Schleutker, Johanna

    AU - Vahteristo, Pia

    PY - 2008

    Y1 - 2008

    N2 - "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."

    AB - "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."

    KW - 311 Basic medicine

    KW - Obstetrics and gynecology

    U2 - 10.1038/ejhg.2008.43

    DO - 10.1038/ejhg.2008.43

    M3 - Article

    VL - 16

    SP - 983

    EP - 991

    JO - European Journal of Human Genetics

    JF - European Journal of Human Genetics

    SN - 1018-4813

    IS - 8

    ER -