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Many women with rogue genes that carry an 80 per cent lifetime chance of breast cancer have no idea that they are at risk, as the mutations responsible were passed on by their fathers.
Research in the United States has found that mutations in the BRCA1 and BRCA2 genes, which account for up to 10 per cent of all breast cancers, are just as likely to be inherited from fathers as from mothers.
As men do not generally get breast cancer, their genetic legacy often remains hidden from their daughters. A mother with a defective gene is likely to develop the disease herself, alerting her daughter to the danger.
A woman who inherits it from her father, however, has no way of knowing that anything is wrong, unless she has relatives with breast cancer on the paternal side of her family.
This is important because women with one of the mutations are less likely to die of breast cancer if they know about their genetic status. They can be screened regularly for abnormalities, and many opt for preventive mastectomies.
Mary-Claire King, Professor of Genome Sciences and Medicine at the University of Washington, who led the study, said that many women at risk from the defect were unaware that they could benefit from genetic tests.
“Mutations in BRCA1 and BRCA2 are inherited from fathers as often as from mothers, although fathers are rarely affected with breast cancer,” she said. “So if a family is small, there may be no warning that a mutation is present.”
About one in every thousand British women carry a damaged version of the BRCA1 gene, and about one in seven hundred have a faulty copy of BRCA2. A typical woman has a one in ten chance of contracting breast cancer at some point in her life, but the risk increases to 82 per cent if she has a defective copy of either gene.
Mutations in BRCA1 and BRCA2 are especially likely to underlie breast cancer in younger women. A woman with one of the mutations has a 20 per cent chance of developing the disease by the age of 40, and a 50 per cent chance by the age of 60. The defects also add to the risk of ovarian cancer.
The US research is the most comprehensive yet of women with the mutations and their families. It involved more than 1,000 Ashkenazi Jewish women with breast cancer: the closed marriage patterns of this community have led to comparatively few mutations in either gene to accumulate, making them simpler to study. The results are published today in the journal Science.
Of 104 women with defective versions of BRCA1 or BRCA2, exactly half did not have a history of breast cancer in the immediate family. In almost all these cases, the mutation had been inherited from the father.
The findings suggest that women should cast the net more widely than their mother, grandmothers and maternal aunts and cousins when trying to assess their genetic risk of breast cancer.
Julie Gralow, of the University of Washington, said: “There is a misconception out there, even among physicians, that the mutation is always passed down by the mother, but it can also come from the father.”
Her colleague Elizabeth Swisher said: “It’s very important that a woman try to get as much information as she can about her father’s side of the family, when gathering a medical history. It’s wise for a woman to ask all her older relatives if they remember anyone in the family with cancer. These questions are becoming more challenging because people are now having smaller families, so there are fewer relatives to provide any warning of the mutation.”
The study also found encouraging evidence that the lifestyle of women with one of the mutations can influence whether and when they develop the disease. Women who exercised regularly and avoided becoming obese as teenagers were likely to develop breast cancer later than those who did not.
“It was a surprise, but a source of hope, to learn that factors over which we have some control made a difference in the age at which these highest-risk women developed breast cancer,” Professor King said. “Women with inherited mutations were at extremely high risk, but exercise and appropriate weight during their adolescent years delayed the onset of breast cancer.”
Jessica Mandel, the research co-ordinator of the study, said that doctors should consider genetic testing for all breast cancer patients.
“It is appropriate for healthcare providers to consider referring breast or ovarian cancer patients for genetic counselling, even if the patient does not have an extensive family history of cancer and particularly if the cancer arises early in life,” she said.
“Genetic counsellors can draw upon the results of this study to help women to make medical decisions that best suit their and their families’ needs related to cancer assessment and cancer prevention.”
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