Constitutional genetic variation at the human aromatase gene (Cyp19) and breast cancer risk
| Autor: | N Siegelmann-Danieli, K H Buetow |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Adult
Cancer Research oestrogens Molecular Sequence Data Breast Neoplasms Locus (genetics) Cyp19 aromatase gene Aromatase breast cancer Breast cancer Risk Factors Genetic variation Genotype medicine Humans Genetic Predisposition to Disease Amino Acid Sequence Age of Onset Allele Genotyping Alleles Aged DNA Primers Genetics Polymorphism Genetic biology Genetic Variation Cancer Regular Article DNA Neoplasm Sequence Analysis DNA Middle Aged medicine.disease Pedigree Oncology biology.protein Female |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/sj.bjc.6690071 |
| Popis: | The activity of the aromatase enzyme, which converts androgens into oestrogens and has a major role in regulating oestrogen levels in the breast, is thought to be a contributing factor in the development of breast cancer. We undertook this study to assess the role of constitutional genetic variation in the human aromatase gene (Cyp19) in the development of this disease. Our genotyping of 348 cases with breast cancer and 145 controls (all Caucasian women) for a published tetranucleotide repeat polymorphism at intron 4 of the Cyp19 gene revealed the presence of six common and two rare alleles. Contingency table analysis revealed a significant difference in allelic distribution between cases and controls (χ2 5df = 13.52, P = 0.019). The allele measuring 171 bp was over-represented in cases; of 14 individuals homozygous for this allele, 13 were cases. These individuals had a higher incidence of cancer in family members and an earlier age at diagnosis than other cases. In sequencing Cyp19's coding exons and regulatory regions, we discovered a perfect association between a silent polymorphism (G→A at Val80) and the high-risk genotype. Our conclusion is that constitutional genetic variation at the Cyp19 locus is associated with the risk of developing breast cancer, with the 171-bp allele serving as the high-risk allele. © 1999 Cancer Research Campaign |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|