Most Breast Cancer May Be Inherited, Study Finds

By Richard Woodman

LONDON May 4, 2002 (Reuters) - Women who have an identical twin sister with breast cancer are at least three times more likely than average to develop the disease, according to research released on Saturday.

Where one twin develops breast cancer at an early age, the other has a high chance of doing likewise, Cancer Research UK scientist Professor Julian Peto told the Oncogenomics conference in Dublin.

According to Peto, the findings suggest that inheritance is much more important in the disease than previously thought.

"We now think that many, possibly the majority, of breast cancers occur in a minority of women with an inherited risk. Identifying and monitoring these susceptible women is going to be an important challenge," he said in a statement.

The epidemiologist analyzed data collected at the University of Southern California in Los Angeles covering 1,300 pairs of identical twins and 1,000 pairs of non-identical twins, where one twin had already developed breast cancer.

The unaffected twins were followed for several years to find out how many would develop the disease.

He found that at least one-third of the identical twins were destined to develop breast cancer at some stage in their lives, compared with just one-ninth of women in the population as a whole.

Non-identical twins of breast cancer patients had a much smaller risk of the disease. This suggests identical twins gain their increased risk by inheriting the same set of genes as their sister with cancer, rather than through sharing the womb, or being brought up together.

The study also showed that where one twin developed cancer at an early age, the other was likely to follow suit. Of women whose twin sisters had developed breast cancer before the age of 40, a quarter went on to get the disease in the next 20 years. By contrast, only four per cent of the female population as a whole developed breast cancer before the age of 60.

Strangely though, twins of women diagnosed before the age of 40 were at no higher risk of breast cancer in later life than twins of patients diagnosed after age 50. Their risk just increased at an earlier age.

"It"s all rather puzzling, but it seems breast cancer genes are doing two different things," Peto said. "Some genes seem to act as timer switches, determining when a woman"s risk of breast cancer should begin, while other genes dictate how big the risk will be.

"It"s like a radio alarm clock, with some genes behaving as the timer and others as the volume control."

Faulty versions of the BRCA1 and BRCA2 genes are known to greatly increase the risk of breast cancer, but these only account for about two per cent of cases. Inherited risk is probably more often caused by a combination of genes, each with a modest effect, the charity said.

Two weeks ago, scientists from The Institute of Cancer Research and Cancer Research UK"s Epidemiology Unit in Cambridge reported the discovery of one such gene, CHK2.

"Knowing that the identical twins of women with breast cancer have such a high risk is of practical use, since we can carefully monitor and counsel these women more effectively," said Sir Paul Nurse, the charity"s interim Chief Executive.

"The research will also play a vital role in clarifying our picture of how the disease develops and particularly how a woman"s genes can combine to increase her risk of the disease."


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