Is there a genetic anticipation in breast and/or ovarian cancer families with the germline c.3481_3491del11 mutation?
Autor: | E. Luporsi, E. Albuisson, R. El Tannouri, P. Jonveaux |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Oncology Adult Cancer Research medicine.medical_specialty Heterozygote Mothers Pedigree chart 03 medical and health sciences 0302 clinical medicine Breast cancer Internal medicine Epidemiology Genetics Medicine Humans Genetic Predisposition to Disease Age of Onset Genetics (clinical) Germ-Line Mutation Genetic testing Aged Retrospective Studies Sequence Deletion medicine.diagnostic_test Base Sequence business.industry Anticipation Genetic BRCA1 Protein Middle Aged medicine.disease Prognosis Survival Analysis Human genetics 030104 developmental biology 030220 oncology & carcinogenesis Mutation (genetic algorithm) Cohort Hereditary Breast and Ovarian Cancer Syndrome Female business Ovarian cancer |
Zdroj: | Familial cancer. 17(1) |
ISSN: | 1573-7292 |
Popis: | The aim of the current analysis is to evaluate any differences of breast or ovarian cancer age at diagnosis between mothers and daughters carrying the c.3481_3491del11 mutation in the BRCA1 gene. A study cohort of 38 women carrying the c.3481_3491del11 mutation and affected by first breast or ovarian cancer who reported a first breast or ovarian cancer in their mother carrying the c.3481_3491del11 mutation, was identified in 37 different families including members with breast and/or ovarian cancer at the Oncology Institute of Lorraine. Twelve mothers underwent genetic testing. Twenty-five pairs of the 38 mothers-daughters pairs with c.3481_3491del11 mutation were affected by breast cancer and 13 pairs by ovarian cancer. Clinical and genetic data were collected from medical files and family pedigrees. Analyses were conducted for each cancer type. We investigated an early breast cancer detection effect due to early screening programs and also an increased breast tumor aggression. Since major improvements in breast cancer clinical management and imaging techniques appeared after 1980, we compared the age at breast cancer diagnosis and the age at death in mothers and daughters before and after 1980, first, in the group of women including mothers and daughters taken together and then in mothers and daughters separately. The mean age at breast cancer diagnosis was 45.28 ± 10.27 years in mothers and 39.80 ± 7.79 years in daughters (p = 0.026). The difference of age at ovarian cancer diagnosis in mother-daughter pairs was 8.62 ± 12.76 years (p = 0.032). When considering the group of women including mothers and daughters taken together, no significant difference of age at breast cancer diagnosis was found between women affected before 1980 and those affected after 1980 (p = 0.577). However, the age at death increased in these women after 1980 (p = 0.026). Comparison of age at breast cancer diagnosis in mothers and daughters separately, showed that daughters were affected at an earlier age after 1980 (p = 0.002). Daughters had a poor prognosis and died earlier than mothers after 1980. Our results may have reflected genetic anticipation in c.3481_3491del11 mutation breast and ovarian cancer families. In order to confirm our findings, a larger cohort would provide more precision to the difference of ages at breast or ovarian cancer diagnosis between mothers and daughters and more powerful statistical analyses. Increased aggression in daughters’ tumors compared to those of mothers could be also considered as a parameter of genetic anticipation. Complete information on tumor profile and proliferation would allow us to study genetic anticipation by comparing the tumor phenotypes between mothers and daughters in the future. |
Databáze: | OpenAIRE |
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