Breast and ovarian cancers related to BRCA mutations appear to be diagnosed at an earlier age in later generations, concludes a US study in "Cancer".
Women with hereditary breast and ovarian cancer syndrome (HBOC) related to the breast cancer (BRCA) genes have an elevated risk of developing both breast and/or ovarian cancer.
A meta-analysis of lifetime risk of breast cancer was 47 to 66 %in BRACA1 carriers and 40 to 57% in BRACA2 carriers, and the risk of developing ovarian cancer was 35% to 46% and 13% to 23% respectively. In other genetic conditions, such as Huntingdon's disease and Fragile X syndrome, the disease has been found to occur at younger ages in subsequent generations.
In the current study, Jennifer Litton and colleagues from MD Anderson Cancer Center (Houston, Texas, US) decided to investigate whether this phenomenon known as "anticipation" occurred in breast cancers related to BRCA mutations.
In the study the investigators evaluated families referred to the Clinical Cancer Genetic Program at the MD Anderson Cancer Center. Altogether 132 BRCA positive women were indentified in the study (generation 2), 106 of whom could be paired with a family member in the previous generation (generation 1) who had been diagnosed with a BRCA-related cancer (either breast cancer or ovarian).
The results show a median age at diagnosis of 48 years in the older generation (generation 1, range 30 to 72 years), and 42 years in the younger generation (generation 2, range 28 to 55 years) (P<.0001). The estimated change in the expected age at onset for the entire cohort was 7.9 years (P<.0001).
"With the onset of genetic testing ...providing guidance for the timing of screening and prophylactic interventions will be critical to preventing cancers in future generations," write the authors.
Current guidelines published by the NCCN, they say, suggest that screening should be initiated for HBOC-related breast cancer at age 25 years or five to ten years earlier than the age at earliest diagnosis.
"If true genetic anticipation is observed with this syndrome, then monitoring for these shifts in age at diagnosis in future generations will be required to better prepare caregivers and patients with regard to the timing of counselling and interventions," they write.
J K Litton, K Ready, H Chen, et al. Earlier age of onset of BRCA mutation-related cancers in subsequent generations. Cancer. Doi: 10.1002/cncr.26284.
(03 Dec 2013)