Increased risk of cancer in patients with fumarate hydratase germline mutation

Heli Lehtonen, Maija Kiuru, Sanna Ylisaukko-oja, Reijo Salovaara, Riitta Herva, Pasi Koivisto, Outi Vierimaa, Kristiina Aittomäki, Eero Pukkala, Virpi Launonen, Lauri A Aaltonen, Heli Lehtonen

    Research output: Contribution to journalArticleScientificpeer-review

    Abstract

    Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a tumour predisposition syndrome caused by heterozygous germline mutations in the fumarate hydratase (FH) gene. The condition is characterised by predisposition to benign leiomyomas of the skin and the uterus, renal cell carcinoma (RCC), and uterine leiomyosarcoma (ULMS). To comprehensively examine the cancer risk and tumour spectrum in Finnish FH mutation positive families, genealogical and cancer data were obtained from 868 individuals. The cohort analysis of the standardised incidence ratios (SIR) was analysed from 256 individuals. FH mutation status was analysed from all available individuals (n = 98). To study tumour spectrum in FH mutation carriers, loss of the wild type allele was analysed from all available tumours (n = 22). The SIR was 6.5 for RCC and 71 for ULMS. The overall cancer risk was statistically significantly increased in the age group of 15-29 years, consistent with features of cancer predisposition families in general. FH germline mutation was found in 55% of studied individuals. Most RCC and ULMS tumours displayed biallelic inactivation of FH, as did breast and bladder cancers. In addition, several benign tumours including atypical uterine leiomyomas, kidney cysts, and adrenal gland adenomas were observed. The present study confirms with calculated risk ratios the association of early onset RCC and ULMS with FH germline mutations in Finns. Some evidence for association of breast and bladder carcinoma with HLRCC was obtained. The data enlighten the organ specific malignant potential of HLRCC.
    Original languageEnglish
    JournalJournal of Medical Genetics
    Volume43
    Issue number6
    Pages (from-to)523-526
    Number of pages4
    ISSN0022-2593
    DOIs
    Publication statusPublished - 2006
    MoE publication typeA1 Journal article-refereed

    Fields of Science

    • 311 Basic medicine

    Cite this

    Lehtonen, H., Kiuru, M., Ylisaukko-oja, S., Salovaara, R., Herva, R., Koivisto, P., ... Lehtonen, H. (2006). Increased risk of cancer in patients with fumarate hydratase germline mutation. Journal of Medical Genetics, 43(6), 523-526. https://doi.org/10.1136/jmg.2005.036400
    Lehtonen, Heli ; Kiuru, Maija ; Ylisaukko-oja, Sanna ; Salovaara, Reijo ; Herva, Riitta ; Koivisto, Pasi ; Vierimaa, Outi ; Aittomäki, Kristiina ; Pukkala, Eero ; Launonen, Virpi ; Aaltonen, Lauri A ; Lehtonen, Heli. / Increased risk of cancer in patients with fumarate hydratase germline mutation. In: Journal of Medical Genetics. 2006 ; Vol. 43, No. 6. pp. 523-526.
    @article{d57a42a73bc94f979fa5b281437b50e0,
    title = "Increased risk of cancer in patients with fumarate hydratase germline mutation",
    abstract = "Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a tumour predisposition syndrome caused by heterozygous germline mutations in the fumarate hydratase (FH) gene. The condition is characterised by predisposition to benign leiomyomas of the skin and the uterus, renal cell carcinoma (RCC), and uterine leiomyosarcoma (ULMS). To comprehensively examine the cancer risk and tumour spectrum in Finnish FH mutation positive families, genealogical and cancer data were obtained from 868 individuals. The cohort analysis of the standardised incidence ratios (SIR) was analysed from 256 individuals. FH mutation status was analysed from all available individuals (n = 98). To study tumour spectrum in FH mutation carriers, loss of the wild type allele was analysed from all available tumours (n = 22). The SIR was 6.5 for RCC and 71 for ULMS. The overall cancer risk was statistically significantly increased in the age group of 15-29 years, consistent with features of cancer predisposition families in general. FH germline mutation was found in 55{\%} of studied individuals. Most RCC and ULMS tumours displayed biallelic inactivation of FH, as did breast and bladder cancers. In addition, several benign tumours including atypical uterine leiomyomas, kidney cysts, and adrenal gland adenomas were observed. The present study confirms with calculated risk ratios the association of early onset RCC and ULMS with FH germline mutations in Finns. Some evidence for association of breast and bladder carcinoma with HLRCC was obtained. The data enlighten the organ specific malignant potential of HLRCC.",
    keywords = "311 Basic medicine",
    author = "Heli Lehtonen and Maija Kiuru and Sanna Ylisaukko-oja and Reijo Salovaara and Riitta Herva and Pasi Koivisto and Outi Vierimaa and Kristiina Aittom{\"a}ki and Eero Pukkala and Virpi Launonen and Aaltonen, {Lauri A} and Heli Lehtonen",
    year = "2006",
    doi = "10.1136/jmg.2005.036400",
    language = "English",
    volume = "43",
    pages = "523--526",
    journal = "Journal of Medical Genetics",
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    Lehtonen, H, Kiuru, M, Ylisaukko-oja, S, Salovaara, R, Herva, R, Koivisto, P, Vierimaa, O, Aittomäki, K, Pukkala, E, Launonen, V, Aaltonen, LA & Lehtonen, H 2006, 'Increased risk of cancer in patients with fumarate hydratase germline mutation', Journal of Medical Genetics, vol. 43, no. 6, pp. 523-526. https://doi.org/10.1136/jmg.2005.036400

    Increased risk of cancer in patients with fumarate hydratase germline mutation. / Lehtonen, Heli; Kiuru, Maija; Ylisaukko-oja, Sanna; Salovaara, Reijo; Herva, Riitta; Koivisto, Pasi; Vierimaa, Outi; Aittomäki, Kristiina; Pukkala, Eero; Launonen, Virpi; Aaltonen, Lauri A; Lehtonen, Heli.

    In: Journal of Medical Genetics, Vol. 43, No. 6, 2006, p. 523-526.

    Research output: Contribution to journalArticleScientificpeer-review

    TY - JOUR

    T1 - Increased risk of cancer in patients with fumarate hydratase germline mutation

    AU - Lehtonen, Heli

    AU - Kiuru, Maija

    AU - Ylisaukko-oja, Sanna

    AU - Salovaara, Reijo

    AU - Herva, Riitta

    AU - Koivisto, Pasi

    AU - Vierimaa, Outi

    AU - Aittomäki, Kristiina

    AU - Pukkala, Eero

    AU - Launonen, Virpi

    AU - Aaltonen, Lauri A

    AU - Lehtonen, Heli

    PY - 2006

    Y1 - 2006

    N2 - Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a tumour predisposition syndrome caused by heterozygous germline mutations in the fumarate hydratase (FH) gene. The condition is characterised by predisposition to benign leiomyomas of the skin and the uterus, renal cell carcinoma (RCC), and uterine leiomyosarcoma (ULMS). To comprehensively examine the cancer risk and tumour spectrum in Finnish FH mutation positive families, genealogical and cancer data were obtained from 868 individuals. The cohort analysis of the standardised incidence ratios (SIR) was analysed from 256 individuals. FH mutation status was analysed from all available individuals (n = 98). To study tumour spectrum in FH mutation carriers, loss of the wild type allele was analysed from all available tumours (n = 22). The SIR was 6.5 for RCC and 71 for ULMS. The overall cancer risk was statistically significantly increased in the age group of 15-29 years, consistent with features of cancer predisposition families in general. FH germline mutation was found in 55% of studied individuals. Most RCC and ULMS tumours displayed biallelic inactivation of FH, as did breast and bladder cancers. In addition, several benign tumours including atypical uterine leiomyomas, kidney cysts, and adrenal gland adenomas were observed. The present study confirms with calculated risk ratios the association of early onset RCC and ULMS with FH germline mutations in Finns. Some evidence for association of breast and bladder carcinoma with HLRCC was obtained. The data enlighten the organ specific malignant potential of HLRCC.

    AB - Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a tumour predisposition syndrome caused by heterozygous germline mutations in the fumarate hydratase (FH) gene. The condition is characterised by predisposition to benign leiomyomas of the skin and the uterus, renal cell carcinoma (RCC), and uterine leiomyosarcoma (ULMS). To comprehensively examine the cancer risk and tumour spectrum in Finnish FH mutation positive families, genealogical and cancer data were obtained from 868 individuals. The cohort analysis of the standardised incidence ratios (SIR) was analysed from 256 individuals. FH mutation status was analysed from all available individuals (n = 98). To study tumour spectrum in FH mutation carriers, loss of the wild type allele was analysed from all available tumours (n = 22). The SIR was 6.5 for RCC and 71 for ULMS. The overall cancer risk was statistically significantly increased in the age group of 15-29 years, consistent with features of cancer predisposition families in general. FH germline mutation was found in 55% of studied individuals. Most RCC and ULMS tumours displayed biallelic inactivation of FH, as did breast and bladder cancers. In addition, several benign tumours including atypical uterine leiomyomas, kidney cysts, and adrenal gland adenomas were observed. The present study confirms with calculated risk ratios the association of early onset RCC and ULMS with FH germline mutations in Finns. Some evidence for association of breast and bladder carcinoma with HLRCC was obtained. The data enlighten the organ specific malignant potential of HLRCC.

    KW - 311 Basic medicine

    U2 - 10.1136/jmg.2005.036400

    DO - 10.1136/jmg.2005.036400

    M3 - Article

    VL - 43

    SP - 523

    EP - 526

    JO - Journal of Medical Genetics

    JF - Journal of Medical Genetics

    SN - 0022-2593

    IS - 6

    ER -

    Lehtonen H, Kiuru M, Ylisaukko-oja S, Salovaara R, Herva R, Koivisto P et al. Increased risk of cancer in patients with fumarate hydratase germline mutation. Journal of Medical Genetics. 2006;43(6):523-526. https://doi.org/10.1136/jmg.2005.036400