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Published in:

01-06-2010

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

Authors: Pia Vahteristo, Taru A. Koski, Laura Näätsaari, Maija 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 Launonen, Rainer Lehtonen

Published in: Familial Cancer | Issue 2/2010

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 mutation carriers 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.

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Title: No evidence for a genetic modifier for renal cell cancer risk in HLRCC syndrome
Authors: Pia Vahteristo
Taru A. Koski
Laura Näätsaari
Maija 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 Launonen
Rainer Lehtonen
Publication date: 01-06-2010
Publisher: Springer Netherlands
Published in: Familial Cancer / Issue 2/2010
Print ISSN: 1389-9600
Electronic ISSN: 1573-7292
DOI: https://doi.org/10.1007/s10689-009-9312-2

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