Is there a genetic anticipation in breast and/or ovarian cancer families with the germline c.3481_3491del11 mutation?

• Published in: Familial cancer 2018, Vol.17 (1), p.5-14
• Main Authors: El Tannouri, R., Albuisson, E., Jonveaux, P., Luporsi, E.
• Format: Article
• Language: English
• Subjects: Adult; Age; Age of Onset; Aged; Anticipation, Genetic; Base Sequence - genetics; Biomedical and Life Sciences; Biomedicine; BRCA1 protein; BRCA1 Protein - genetics; Breast cancer; Cancer Research; Diagnosis; Epidemiology; Female; Genetic Predisposition to Disease; Genetic screening; Germ-Line Mutation; Hereditary Breast and Ovarian Cancer Syndrome - genetics; Hereditary Breast and Ovarian Cancer Syndrome - mortality; Heterozygote; Human Genetics; Humans; Mammography; Middle Aged; Mothers; Mutation; Original Article; Ovarian cancer; Prognosis; Retrospective Studies; Sequence Deletion; Statistical analysis; Survival Analysis; Tumors
• ISSN: 1389-9600; 1573-7292
• DOI: 10.1007/s10689-017-9999-4

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 thos