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Gastric cancer in three relatives of a patient with a biallelic IL12RB1 mutation

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Abstract

IL-12Rβ1 deficiency, also known as immunodeficiency 30 (IMD30, OMIM 614891), is a rare immunodeficiency syndrome caused by biallelic mutations in IL12RB1. Three second-degree relatives of a patient with this syndrome, all women, developed intestinal-type gastric cancer (GC). In the Netherlands the incidence of non-cardia GC in women is only 7 per 100,000 person years. Both relatives that were available for testing proved to be heterozygous for the familial IL12RB1 mutation, suggesting there might be a causal relation. Testing 29 index patients from families with early onset and/or a familial history of GC for germline mutations in both IL12RB1 and IL12RB2, that encodes the binding partner of IL-12Rβ1, did not reveal other germline mutations in these genes. Therefore heterozygous inactivating mutations in IL12RB1 and IL12RB2 are unlikely to be frequently involved in GC predisposition. Additional research in families with IL12RB1 mutations is required to determine whether carriers of IL12RB1 mutations have an increased (gastric) cancer risk.

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Acknowledgments

The authors would like to thank Heleen Diepstra for excellent assistance with the data analysis.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Human Genetics, Radboud university medical center, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands

    Ingrid P. Vogelaar, Nicoline Hoogerbrugge & Marjolijn J. L. Ligtenberg

  2. Department of Pathology, Radboud university medical center, Nijmegen, The Netherlands

    Rachel S. van der Post, J. Han J. M. van Krieken & Marjolijn J. L. Ligtenberg

  3. Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands

    Esther van de Vosse

  4. Department of Clinical Genetics, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands

    Encarna Gómez García

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  1. Ingrid P. Vogelaar
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  3. Esther van de Vosse
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Correspondence to Encarna Gómez García.

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Vogelaar, I.P., van der Post, R.S., van de Vosse, E. et al. Gastric cancer in three relatives of a patient with a biallelic IL12RB1 mutation. Familial Cancer 14, 89–94 (2015). https://doi.org/10.1007/s10689-014-9764-x

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  • DOI: https://doi.org/10.1007/s10689-014-9764-x

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