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What are the BRCA1 and BRCA2 genes? Primer on genetic mutations linked to cancers

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(GlobalPost/GlobalPost)

TORONTO - Angelina Jolie's bombshell revelation of her double mastectomy due to a genetic cancer risk has brought renewed attention to specific genes linked to the development of both breast and ovarian cancers.

The Oscar-winning actress revealed in an op-ed piece in the New York Times that she carries the "faulty" BRCA1 gene and opted to remove her breasts as a preventive measure.

BRCA1 stands for breast cancer susceptibility gene 1. Both BRCA1 and BRCA2 are genes known as tumour suppressors, which normally prevent cancer from developing.

Women found to have mutations in the genes have a very high risk of developing breast and ovarian cancers, said Kelly Metcalfe, an associate professor in the faculty of nursing at the University of Toronto. Risks can change depending on the woman's personal situation, looking at factors such as age and family history, she added.

The genetic mutations are not common, said Dr. Barb McGillivray, medical director of the hereditary cancer program at the B.C. Cancer Agency.

"About one in 500 to one in 1,000 individuals will carry a mutation or a gene change in one or another of these genes," she said from Abbotsford, B.C.

Certain populations are more likely to carry the genetic mutation. Ashkenazi Jews of Eastern European ancestry have about a one in 40 chance of having the mutated BRCA gene — considerably higher than the general population, says the Canadian Cancer Society.

"It's generally when populations tend to stay together and don't have offspring with people from other types of ethnicities that we see these mutations tend to stay within one group of individuals," said Metcalfe, an adjunct scientist at the Women’s College Research Institute.

According to the Cancer Society, the chance of breast and ovarian cancers being linked to the mutated genes are highest among the following families:

— Those with a family history of breast or ovarian cancer;

— Early onset of breast cancer in one or more female relatives before age 50;

— Breast and ovarian cancer in a single relative;

— Family members developing cancer in both breasts;

— A male relative with breast cancer.

What distinguishes BRCA1 and BRCA2 genes is where they're located in the chromosomes, said Metcalfe. There are also slight differences in terms of the types of cancers associated with the two genes.

Carriers of the BRCA1 gene mutation have a slightly increased risk of ovarian cancer compared to those with BRCA2. But BRCA2 carriers have risks of different types of cancers, including pancreatic cancer and melanoma, said Metcalfe.

For men with the BRCA2 mutation, there's a heightened risk of both prostate and breast cancers, she added.

Metcalfe said there are certain criteria an individual must meet to be eligible for genetic testing, including a strong family history of cancer, young ages of onset of cancer within the family and being a member of ethnic groups known to be affected.

"So if you're a woman with breast cancer and you're Jewish, because we know you have a higher risk of having one of these mutations, you're eligible for testing. But there are very strict guidelines on who's eligible."

Canadians who don't meet the criteria but still want to be tested can opt to do so south of the border — and at a steep cost. Metcalfe said U.S.-based Myriad Genetics will conduct the test for about $3,000.

In Canada, the lifetime risk of breast cancer for any woman is between one in eight and one in nine, or between 12 and 13 per cent, said McGillivray.

A woman with a BRCA1 or BRCA2 mutation has a lifetime risk of up to 85 per cent for getting breast cancer. By having a prophylactic (or risk-reducing) mastectomy — as Jolie has done — she reduces her risk to under five per cent, she noted.

As for ovarian cancer, women with a mutated BRCA1 gene have a 25 to 65 per cent lifetime risk of developing the disease, says the Cancer Society. Those with a mutated BRCA2 gene have a 15 to 20 per cent chance of developing ovarian cancer.

"The problem with ovarian cancer ... is we don't have good ways to pick it up early," said McGillivray. As a result, more women actually opt to voluntarily remove their fallopian tubes and ovaries, she noted.

Part of McGillivray's hereditary cancer program involves the operation of a high-risk clinic in Vancouver for women who don't have cancer but are found to have one of the genetic mutations. Participants can attend for ongoing surveillance, including MRIs and mammograms.

In the last year, McGillivray said among the 300 women in the program who didn't have cancer, 27 per cent chose to have mastectomies. Fifty-five per cent chose to have their tubes and ovaries removed.

"Generally, women make the decision about having ovaries and tubes out when they've had their families, when they're approaching the age of menopause," she said.

Women may choose to have their breasts removed after they've had children so they've had the opportunity to breastfeed, McGillivray said. "But women might choose that surgery at any point.... It depends on how your family history has affected you, what your own experience has been."

Opting for a preventive mastectomy can be an emotional struggle for many women, said Metcalfe. But for those at a high risk of developing cancer, having the surgery can reduce cancer-related stress.

"Most women that I've spoken to actually describe waking up from the surgery thinking: 'I no longer have to be consumed by that thought about when or if I will develop breast cancer.' So for those women, it offers psychological benefits as well."

http://www.globalpost.com/dispatch/news/the-canadian-press/130514/what-are-the-brca1-and-brca2-genes-primer-genetic-mutations-