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Breast cancer risk genes from mum or dad? It could affect diagnosis age

19 December 2011

By Dr Rebecca Robey

Appeared in BioNews 638

Women who inherit breast cancer risk genes from their father may be diagnosed with, or even develop, the disease several years earlier than those who inherit the same genes from their mother. This may have implications for screening and treatment strategies for those at risk of hereditary breast cancer.

Researchers from Long Island Jewish (LIJ) School of Medicine and Feinstein Institute for Medical Research, New York, USA, examined the age of diagnosis of breast or ovarian cancer. In the 130 women analysed, they found that those who inherited a mutated copy of BRCA1 or BRCA2 from their father were diagnosed between six and nine years earlier than those inheriting it from their mother.

'No one had ever conducted a study to look at the parent-of-origin effects', said Dr Iuliana Shapira, lead author of the study and director of cancer genetics at Monter Cancer Center. 'Cancer penetrance in mutation carriers may be determined by the parent origin of BRCA mutation'.

Among the breast cancer patients, 28 women had inherited a BRCA1 risk variant from their fathers and 29 from their mothers. Of those with BRCA2 risk variants, 24 had inherited this paternally and 21 maternally. Overall, the average age of breast cancer diagnosis was 43 (in a range of 24-78), but the team noticed there were marked differences between the diagnosis age of those with genes inherited from their fathers as opposed to their mothers.

Women with paternal BRCA1 were diagnosed with breast cancer at an average age of 38, compared to 45 for women with maternal BRCA1. Similarly, women with paternal BRCA2 were diagnosed, on average, at 41, compared to 50 for those with maternal BRCA2.

BRCA1 and BRCA2 are tumour suppressor genes, and only one mutation needs to be inherited to increase the chance of developing breast or ovarian cancer. Those with a mutated copy have between a 50 and 80 percent chance of developing cancer, which is estimated to be about five times higher than a woman without such a mutation.

Dr Shapira commented: 'If this observation is duplicated in larger cohorts, the results will have important implications for recommendation of surgical risk reduction in BRCA mutation carriers… That would mean that doctors might think about watching and waiting in young woman with BRCA mutations inherited from her mother's family and being more aggressive in young women who inherited the mutation from their father's side'.

The researchers also compared age of diagnosis of ovarian cancer in six women with paternal and ten women with maternal BRCA1 risk mutants, and seven women with paternal and three women with maternal BRCA2.

The overall average age of diagnosis was 51 (in a range of 21-70) and they observed no differences between those who inherited risk genes from their paternal versus maternal lineages.

These preliminary findings were presented at the San Antonio Breast Cancer Symposium on 8 December 2011, but have yet to be published in a peer-review journal.

SOURCES & REFERENCES
US News Health Day | 08 December 2011
 
Newswise | 12 December 2011
 
The Scientist | 13 December 2011
 
Parent of Origin of BRCA Mutation May Determine Age at Breast Cancer Diagnosis
San Antonio Breast Cancer Symposium - poster P2-13-02 | 08 December 2011
 

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