Genetic Testing and Personal Responsibility

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People do not easily accept change. In the last 100 years or so, humanity has come to grips with new ideas that for thousands of years were practically unheard of. Among them was the concept of germs, which lead to pasteurization and sterilization of surgical instruments, things everyone now takes for granted but were hotly disputed and debated not so very long ago.

Can you imagine the impact this new knowledge had on scientific minds of the day, to say nothing of the effect on mass populations during that time period?

We have changed over time, and will hopefully continue to adjust and adapt to an ever-changing environment and assimilate new knowledge constantly being made available to us.

Some knowledge I recently gained was about women with a family history of breast or ovarian cancer. According to a seminar given this past February called “Genetic Testing and Life Decisions: What Would You Do?” women should meet with a genetic counselor to have their risk for cancer assessed, consider genetic testing and take appropriate precautions.

This was the take-home message given by Olufunmilayo Olopade, M.D., professor of medicine and human genetics at the University of Chicago and the director of the Center for Clinical Cancer Genetics at the university’s hospital, at the seminar.

Those present at the seminar listened to a number of speakers address the subject of genetic testing and female health, and the impact the tests might have on individuals’ lives. A feature film about genetic testing for breast cancer called “In The Family,” which included Olopade’s comments, engaged the interest of the audience.

According to Olopade, women of African ancestry are at greater risk for mortality due to breast cancer than other racial and ethnic groups. Why this is the case is still unknown.

Who gets breast cancer?
Breast cancer is the second most commonly diagnosed cancer, and the second leading cause of cancer death for women. About 40,600 women of an estimated 217,400 new breast cancer cases in the U.S. in 2004 died of the disease.

In the general population, most breast cancers occur in post-menopausal women over age 50.

Five to 10 percent of women with breast cancer have an inherited susceptibility. After gender and age, a family history of breast or ovarian cancer is the single best predictor of the likelihood that a woman will develop these cancers.

Family histories that suggest a hereditary predisposition for breast and ovarian cancer include: family members who have had breast cancer; other multiple cancers in the family, especially prostate; an Ashkenazi (Eastern and Central European) Jewish background.

Genetic mutations
After a long search for changes in DNA sequences that were common in breast-cancer-prone families, particularly Ashkenazi Jews, BRCA 1 was discovered in 1994 and BRCA 2 in 1995. BRCA 1 and 2 are genetic mutations that can increase the likelihood a carrier of the mutation will become ill with breast cancer.

Less than one percent of the general population carries a potentially damaging BRCA 1 mutation.Not everyone with an altered BRCA gene will develop cancer. Women with BRCA mutations most often are diagnosed with breast cancer in their 40s. Women with a BRCA 1 mutation have about a 40 percent chance of developing ovarian cancer by age 70. Women with a BRCA 2 mutation have about a 20 percent risk of developing ovarian cancer by age 70.

Not all breast or ovarian cancers in cancer-prone families are due to BRCA mutations. Mutations in BRCA 1 account for breast or ovarian cancers in 45 percent of families with a history of breast cancer and up to 90 percent in families with a history of both breast and ovarian cancers. BRCA 2 mutations account for breast cancer in about 35 percent of families with a history of breast cancer.

Breast cancer and women of African descent
I was particularly interested in comments made by. Olopade, in the feature film shown at the February seminar.

“Access to genetic counseling and testing are an important part of cancer control. But in this fast-moving area of medicine, some ethnic minorities are being left behind,” Olopade said. “We need to encourage high-risk women from all ethnic groups to get counseling and we need to learn more about what specific test results mean for each racial or ethnic group.”

Olopade, Dr. Rita Nanda, M.D., and colleagues at the Cancer Risk Clinic at the University of Chicago Hospitals, pulled together 10 years of counseling and testing data from the clinic. The researchers at the Cancer Risk Clinic used the data to determine how well they could predict BRCA 1 and BRCA 2 mutations based on family history, among high-risk individuals of both European and African ancestry. They also looked at the range of mutations found in various ethnic groups.

The first thing they noticed was few minority women sought counseling or were referred for testing. Out of 155 families, three were Hispanic and two were Asian. And though about half of patients at the University of Chicago Hospitals are African American, less than one third of families who sought testing were of African ancestry.

They did confirm their test worked just as well for African Americans as it did for other populations. The study found that regardless of ancestry, “early age of diagnosis and a family history of breast and ovarian cancer are the most powerful predictors of mutation status.”

How mutations affect different groups
DNA testing, however, showed that the spectrum of mutations was different for families of African as opposed to European ancestry.

“These mutations are inherited, so they tend to reflect a person’s racial and ethnic ancestry,” Olopade said. The Ashkenazi Jewish mutations are the most common and consistent, but there are distinctive “founder” mutations in BRCA1 and BRCA2 associated with other European ethnic groups, such as the Germans, Dutch or Scots.

As expected, damaging mutations in BRCA1 or BRCA2 were most common in Ashkenazi Jewish families. 69 percent of high-risk women tested (20 out of 29) had a mutation and 85 percent of those mutations were one of three well-documented variants associated with this ethnic group.

“We still have a lot to learn about the ties between genetics and breast cancer in African Americans as well as many other minority groups,” Olopade said. “But we already know enough about the risk factors and the disease to help those most at risk by designing protocols for prevention and early detection.”

It is expected that the study will lead to a more accurate definition of genetic risks, improved clinical risk assessment, and potentially to development of new prevention, early detection, and treatment strategies for young women of African ancestry.

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