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Women Testing Negative for Familial Breast Cancer Gene Still at Increased Risk

Women testing negative for the two inherited breast cancer genes are still at increased risk of developing the disease, suggests research published// ahead of print in the Journal of Medical Genetics.

They should be regularly screened from 35 or 40 onwards, say the authors.

The research team assessed the families of 277 women in whom faults in the breast cancer genes BRCA1 and BRCA2 had been identified.

Faults in these genes account for only around 5% of all diagnosed breast cancers in developed countries. But they substantially increase a woman’s chances of developing early breast and/or ovarian cancer compared with the general population, and “predictive” testing is usually offered to other blood relatives.

Of the 277 women, 190 had breast cancer, 48 had ovarian cancer, and 33 had both. Six were free of the disease.

Among the 531 living female relatives who were tested for the genetic faults, almost half (49%) tested negative. Of these, 28 developed breast cancer and four developed ovarian cancer.

Among the 184 first degree relatives testing negative, 4 different BRCA1 and 2 “phenocopies” were identified, accounting for around one in four test results.

A phenocopy is when a patient develops the condition that a particular gene predisposes them to, but they test negative for the inherited genetic fault. This is likely to be due to other genetic variants (modifier genes) that mimic the physiological changes produced by that specific gene fault.

Thirteen of 107 first degree relatives with breast cancer and a family history of BRCA genes tested negative for these genetic faults.

On the basis of their findings, the authors calculated that first degree relatives testing negative for BRCA1 and 2 had around three times the risk of developing breast cancer by the age of 50 as the general population.

Environmental factors, such as diet, or hormones c ould account for some of the increased risk, but these are only likely to account for around 10% of familial cancers, say the authors.

“If confirmed, these findings have serious implications for the management of these people,” say the authors. They cite recent US guidelines, which recommend that women with a five year chance of developing breast cancer of more than 1.7% should be screened for breast cancer from the age of 35 onwards.

Recent guidance from the National Institute of Health and Clinical Excellence (NICE) in the UK recommends that women with a 10 year risk of 3% should be screened from the age of 40.

In this study, the women testing negative for the inherited genes had 6.4% chance of developing the disease by the age of 50. UK guidance currently states that women testing negative for the genes carry the same risk as the general population.

Source-NewswiseSRM
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