Potential genetic anticipation in hereditary leiomyomatosis-renal cell cancer (HLRCC)

Mei Hua Wong, Chuen Seng Tan, Soo Chin Lee, Yvonne Yong, Aik Seng Ooi, Joanne Ngeow, Min Han Tan

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Hereditary leiomyomatosis-renal cell cancer (HLRCC) is an autosomal dominant disorder characterised by cutaneous leiomyomas, symptomatic uterine leiomyomas and aggressive type II papillary renal cell carcinoma. It is caused by heterozygous mutations in the fumarate hydratase (FH) gene on chromosome 1q43. We present evidence of genetic anticipation in HLRCC syndrome. A comprehensive literature review was performed to determine the potential for genetic anticipation in HLRCC syndrome. The normal random effects model was used to evaluate for genetic anticipation to ensure reduction in bias. A total of 11 FH kindreds with available multi-generational data were identified for analysis. The mean difference in age at diagnosis of RCC between the first and second generation was -18.6 years (95 % CI -26.6 to -10.6, p < 0.001). The mean difference in age at diagnosis of RCC between the first and third generation was -36.2 years (95 % CI -47.0 to -25.4, p < 0.001). No evidence of anticipation for uterine leiomyomas was observed (p = 0.349). We report preliminary evidence of genetic anticipation of RCC in HLRCC syndrome. Additional clinical validation is important to confirm this observation, which may have practical implications on counseling and timing of surveillance initiation. Exploration of the underlying mechanisms of anticipation in HLRCC would be of considerable biological interest.

Original languageEnglish (US)
Pages (from-to)281-289
Number of pages9
JournalFamilial Cancer
Volume13
Issue number2
DOIs
StatePublished - Jun 2014
Externally publishedYes

Keywords

  • Fumarate hydratase
  • Genetic anticipation
  • Hereditary leiomyomatosis-renal cell carcinoma syndrome
  • Krebs cycle
  • Papillary renal cell carcinoma

ASJC Scopus subject areas

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

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