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

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 17b-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.