Analysis of 17β-hydroxysteroid dehydrogenase types 5, 7, and 12 genetic sequence variants in breast cancer cases from French Canadian Families with high risk of breast and ovarian cancer
| Autor: | Marie Plourde, Alexandra Ferland, Penny Soucy, Yosr Hamdi, Martine Tranchant, Francine Durocher, Olga Sinilnikova, Van Luu The, Jacques Simard |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Canada 3-Hydroxysteroid Dehydrogenases 17-Hydroxysteroid Dehydrogenases Endocrinology Diabetes and Metabolism Clinical Biochemistry Breast Neoplasms Single-nucleotide polymorphism Biology Biochemistry Cell Line Endocrinology Breast cancer medicine Genetic predisposition Humans Missense mutation Genetic Predisposition to Disease Promoter Regions Genetic Molecular Biology BRCA2 Protein Ovarian Neoplasms Genetics BRCA1 Protein Haplotype Aldo-Keto Reductase Family 1 Member C3 Cancer Exons Cell Biology Middle Aged medicine.disease Introns Risk factors for breast cancer Mutation Hydroxyprostaglandin Dehydrogenases Molecular Medicine Female Breast disease Apoptosis Regulatory Proteins |
| Zdroj: | The Journal of Steroid Biochemistry and Molecular Biology. 116:134-153 |
| ISSN: | 0960-0760 |
| DOI: | 10.1016/j.jsbmb.2009.05.005 |
| Popis: | A family history and estrogen exposure are well-known risk factors for breast cancer. Members of the 17beta-hydroxysteroid dehydrogenase family are responsible for important steps in the metabolism of androgens and estrogens in peripheral tissues, including the mammary gland. The crucial biological function of 17beta-HSDs renders these genes good candidates for being involved in breast cancer etiology. This study screened for mutations in HSD17B7 and HSD17B12 genes, which encode enzymes involved in estradiol biosynthesis and in AKR1C3, which codes for 17beta-HSD type 5 enzyme involved in androgen and progesterone metabolism, to assess whether high penetrance allelic variants in these genes could be involved in breast cancer susceptibility. Mutation screening of 50 breast cancer cases from non-BRCA1/2 high-risk French Canadian families failed to identify germline likely high-risk mutations in HSD17B7, HSD17B12 and AKR1C3 genes. However, 107 sequence variants were identified, including seven missense variants. Assessment of the impact of missense variants on enzymatic activity of the corresponding enzymes revealed no difference in catalytic properties between variants of 17beta-HSD types 7 and 12 and wild-type enzymes, while variants p.Glu77Gly and p.Lys183Arg in 17beta-HSD type 5 showed a slightly decreased activity. Finally, a haplotype-based approach was used to determine tagging SNPs providing valuable information for studies investigating associations of common variants in these genes with breast cancer risk. |
| Databáze: | OpenAIRE |
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