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Last Updated: Tuesday, 31 October 2006, 00:11 GMT
Family cancer risk 'without gene'
An MRI scan of a breast showing a tumour (Science Photo Library)
BRCA mutations put women at a higher risk of breast cancer
Women with a family history of breast cancer have a greater chance of getting the disease even without inheriting the "high risk" genes, scientists say.

A UK team looked at 277 families with a history of carrying mutated BRCA genes.

They found female members were three times more likely to develop breast cancer than the general population even if they did not carry the genes.

The scientists, writing in the Journal of Medical Genetics, said all women in high-risk families should be screened.

Mutations in the BRCA1 and BRCA2 genes cause about 5% of breast cancers.

Research suggests that if the fault in the gene is inherited, a woman has an 85% chance of developing the disease by the age of 70.

Professor Gareth Evans, the lead author from the department of medical genetics, St Mary's Hospital, Manchester, said: "Up until now when we have found a genetic fault in a family, we have assumed that if you do not have that fault, your risk of breast cancer is no different to anyone else."

There are far too many women in these families who test negative for the mutation but who develop breast cancer
Professor Gareth Evans

But he said his findings suggested otherwise.

The team looked at the families of 277 women who carried the genetic mutation, 190 of whom had breast cancer.

Of their 432 living "first-degree" female relatives (sisters, daughters and mothers), 184 tested negative for the BRCA1 and BRCA2 mutations.

But the researchers found the women who tested negative still carried a higher breast cancer risk than expected.

Calculations based on breast cancer levels in general population suggested just 2% of this group should have developed cancer, when in fact, 6.4% had developed the disease by the age of 50.

Professor Evans said: "Our research has shown there are far too many women in these families who test negative for the mutation but who develop breast cancer."

Screening needed

He said because these women were at "moderate risk" of breast cancer they should be under greater medical surveillance.

"We would suggest these women should be considered for annual breast screening between the ages 40 and 49 in the UK, like the women who carry the genetic faults, rather than being treated like the general population where compulsory screening begins at 50."

Professor Evans said the increased risk was probably due to the fact that the women were inheriting combinations of other genes that gave them a greater predisposition to breast cancer.

"If you look at twin studies, they show that about 27% of breast cancer has an inherited component but only 3% of cancer is down to BRCA1 and 2."

He said other genetic factors must be making up the difference.

Dr Sarah Rawlings, head of policy and information at Breakthrough Breast Cancer, said: "We already know that some women with a strong family history of breast cancer don't carry the faulty BRCA1 and 2 genes.

"This paper provides more information about the genetic risk of breast cancer and further research is now needed to increase our understanding.

"If you're concerned about your family history of breast cancer you should speak to your doctor who will let you know what this means for you."




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