TY - JOUR
T1 - Recurrent candidiasis and early-onset gastric cancer in a patient with a genetically defined partial MYD88 defect
AU - Vogelaar, Ingrid P.
AU - Ligtenberg, Marjolijn J.L.
AU - van der Post, Rachel S.
AU - de Voer, Richarda M.
AU - Kets, C. Marleen
AU - Jansen, Trees J.G.
AU - Jacobs, Liesbeth
AU - Schreibelt, Gerty
AU - de Vries, I. Jolanda M.
AU - Netea, Mihai G.
AU - Hoogerbrugge, Nicoline
AU - Lubinski, Jan
AU - Jakubowska, Anna
AU - Teodorczyk, Urszula
AU - Schackert, Hans K.
AU - Aalfs, Cora M.
AU - Gómez García, Encarna B.
AU - Ranzani, Guglielmina N.
AU - Molinaro, Valeria
AU - van Hest, Liselotte P.
AU - Hes, Frederik J.
AU - Holinski-Feder, Elke
AU - Genuardi, Maurizio
AU - Ausems, Margreet G.E.M.
AU - Sijmons, Rolf H.
AU - Wagner, Anja
AU - van der Kolk, Lizet E.
AU - Pinheiro, Hugo
AU - Oliveira, Carla
AU - Bjørnevoll, Inga
AU - Høberg Vetti, Hildegunn
AU - Han, J.
AU - van Krieken, J. M.
AU - International Gastric Cancer Genetics Group
N1 - Funding Information:
This work was supported by the Radboudumc Center for Oncology, granted in 2010, the Deutsche Krebshilfe Grant 70-2371, the Portuguese Foundation for Science and Technology (FCT) (Projects Ref. FCT PTDC/SAU-GMG/110785/2009 and Post-doc grant SFRH/BPD/79499/2011 to HP “financiados no âmbito do Programa Operacional Temático Factores de Competitividade (COMPETE) e comparticipado pelo fundo Comunitário Europeu FEDER”). M.G.N. was supported by an ERC-Consolidator Grant (310372). The authors would like to thank prof. dr. Carl Figdor for fruitful scientific discussions and Hanna Feunekes for help with the validation work. The H. pylori strains were kindly provided by prof. dr. Christina Vandenbroucke-Grauls and the DNA samples of healthy controls were provided by Margit Schraders, Jaap Oostrik and Muhammad Imran Khan.
Publisher Copyright:
© 2015, The Author(s).
PY - 2016/4/1
Y1 - 2016/4/1
N2 - Gastric cancer is caused by both genetic and environmental factors. A woman who suffered from recurrent candidiasis throughout her life developed diffuse-type gastric cancer at the age of 23 years. Using whole-exome sequencing we identified a germline homozygous missense variant in MYD88. Immunological assays on peripheral blood mononuclear cells revealed an impaired immune response upon stimulation with Candida albicans, characterized by a defective production of the cytokine interleukin-17. Our data suggest that a genetic defect in MYD88 results in an impaired immune response and may increase gastric cancer risk.
AB - Gastric cancer is caused by both genetic and environmental factors. A woman who suffered from recurrent candidiasis throughout her life developed diffuse-type gastric cancer at the age of 23 years. Using whole-exome sequencing we identified a germline homozygous missense variant in MYD88. Immunological assays on peripheral blood mononuclear cells revealed an impaired immune response upon stimulation with Candida albicans, characterized by a defective production of the cytokine interleukin-17. Our data suggest that a genetic defect in MYD88 results in an impaired immune response and may increase gastric cancer risk.
KW - Candidaalbicans
KW - Gastric cancer
KW - Interleukin-17
KW - MYD88
KW - Th17 response
U2 - 10.1007/s10689-015-9859-z
DO - 10.1007/s10689-015-9859-z
M3 - Article
SN - 1389-9600
VL - 15
SP - 289
EP - 296
JO - Familial Cancer
JF - Familial Cancer
IS - 2
ER -