No evidence for a genetic modifier for renal cell cancer risk in HLRCC syndrome

Pia Vahteristo, Taru A. Koski, Laura Näätsaari, Maija Ht Kiuru, Auli Karhu, Riitta Herva, Satu Leena Sallinen, Outi Vierimaa, Erik Björck, Stéphane Richard, Betty Gardie, Didier Bessis, Emmanuel Van Glabeke, Ignacio Blanco, Richard Houlston, Leigha Senter, Marja Hietala, Kristiina Aittomäki, Lauri A. Aaltonen, Virpi LaunonenRainer Lehtonen

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a tumor predisposition syndrome caused by heterozygous germline mutations in the fumarate hydratase (FH) gene. Cutaneous and uterine leiomyomas are the most common clinical manifestations of HLRCC, whereas only approximately 20% of the families display renal cell cancer (RCC). The number of RCC cases in these families varies from one to five. Interestingly, families with multiple RCC cases are mainly found in Finland and the USA. Such aggregation of RCC in only some families and populations has led to the hypothesis that besides FH mutations also other inherited genetic and/or environmental factors may contribute to the malignant kidney tumor formation. To search for such a genetic modifier we have performed a genome-wide linkage analysis in two and an identical by descent analysis in four Finnish HLRCC families with several RCC patients. Additional Finnish and French families were used in fine-mapping and haplotype analyses. The only region compatible with linkage was the locus surrounding the FH gene itself in chromosome 1q43. The genes in the putative candidate region were screened, but no potentially pathogenic alterations were observed. Although these data do not rule out the existence of a genetic modifier, they emphasize the contribution of the FH genotype in HLRCC related RCC. Therefore, as all FH mutationcarriers may have an increased risk for developing renal cancer, counseling and genetic testing should be offered for all HLRCC family members and clinical follow-up should be organized for the mutation carriers.

Original languageEnglish (US)
Pages (from-to)245-251
Number of pages7
JournalFamilial Cancer
Volume9
Issue number2
DOIs
StatePublished - Jun 2010
Externally publishedYes

Keywords

  • Fumarate hydratase
  • Genetic testing
  • HLRCC
  • Modifier
  • Renal cell cancer

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Oncology
  • Genetics(clinical)

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  • Cite this

    Vahteristo, P., Koski, T. A., Näätsaari, L., Kiuru, M. H., Karhu, A., Herva, R., Sallinen, S. L., Vierimaa, O., Björck, E., Richard, S., Gardie, B., Bessis, D., Glabeke, E. V., Blanco, I., Houlston, R., Senter, L., Hietala, M., Aittomäki, K., Aaltonen, L. A., ... Lehtonen, R. (2010). No evidence for a genetic modifier for renal cell cancer risk in HLRCC syndrome. Familial Cancer, 9(2), 245-251. https://doi.org/10.1007/s10689-009-9312-2