• Made available online as an Accepted Preprint 21 January 2008
  • Accepted Preprint first posted online on 21 January 2008

Mutation analysis and characterization of HSD17B2 sequence variants in breast cancer cases from French Canadian families with high risk of breast and ovarian cancer

  1. Jacques Simard1,3
  1. 1Cancer Genomics Laboratory, Oncology and Molecular Endocrinology Research Center, Centre Hospitalier Universitaire de Québec and Laval University, Quebec G1V 4G2, Canada2Plate-Forme Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civil de Lyon/Centre Léon Bérard, 69373 Lyon Cedex 08, France3Canada Research Chair in Oncogenetics
  1. (Correspondence should be addressed to J Simard who is now at Cancer Genomics Laboratory, CHUL Research Center, CHUQ, 2705 Laurier Boulevard, T3-57, Quebec City, Quebec G1V 4G2, Canada; Email: jacques.simard{at}crchul.ulaval.ca)


Estrogen exposure is a risk factor for breast cancer. Given that HSD17B2 gene encodes an enzyme that catalyses estradiol inactivation, it appears as a good candidate breast cancer susceptibility gene. This study was designed to screen for HSD17B2 germline mutations potentially involved in breast cancer predisposition. Our re-sequencing analysis did not identify any deleterious germline mutations, and therefore mutations in HSD17B2 do not explain the clustering of breast cancer cases in non-BRCA1/2 high-risk French Canadian families. However, six sequence variants were identified, including two novel missense variants. Expression assays revealed that p.Ala111Asp and p.Gly160Arg did not alter the catalytic properties of 17β-hydroxysteroid dehydrogenase type 2 enzyme, although p.Ala111Asp appears to affect protein stability resulting in significant decreases in the protein levels, providing valuable information on structure–function relationship.

  • Revision received 28 November 2007
  • Accepted 21 January 2008
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