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Mystery In The Bahamas: A Genetic Whodunit
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Posted by:Feb 5th 2006, 03:35:00 pm

Posted on Tue, Jan. 31, 2006
Mystery in the Bahamas: A genetic whodunit
Breast cancer patients in the island chain are alarmingly young. No one knows why. A genetic whodunit.

When Pamela Williams felt a lump in her breast, she was 34, seven months pregnant and following three sisters who had been diagnosed with breast cancer while in their 30s.

Taken alone, this development would not be particularly remarkable; early-onset breast cancer tends to run in families.

But Williams is Bahamian, which makes her part of a trend that has long mystified doctors in the region: Bahamian breast cancer patients are often shockingly young.

''They told me when I got here,'' said Dr. Theodore Turnquest, a native Bahamian who returned to Nassau a few years ago after finishing his medical training in the United States. ``I was a little skeptical about it, but when I started practicing I became more of a believer.''

Dr. Judith Hurley, a breast cancer specialist at the University of Miami School of Medicine, has noticed the same thing in South Florida women of Bahamian descent.

'A few years ago, I thought, `Another 40-year-old Bahamian. This just isn't right,' '' she said.

That observation prompted Hurley and Turnquest to launch a study that confirmed their hunch: Nearly half of Bahamian breast cancer patients in the study -- 48 percent -- were diagnosed before age 50. In the United States, by comparison, less than one-third of patients are diagnosed before 50.

Now Hurley is trying to figure out why.

While environmental factors cannot be ruled out, the patients' young ages make environment an unlikely contributor, Hurley said.

''Environmental toxins take a long time to affect a person,'' she said.

Certain genetic mutations, on the other hand, predispose women to early-onset cancer, and last year Hurley began studying the genes of Williams and others like her. She hopes to learn whether an unknown but prolific Bahamian woman generations ago bestowed her cancer-prone genes to thousands of descendants.

''In an island population, if you've got a couple of bad genes, they just keep going round and round,'' Hurley said.


In the 1990s, scientists discovered mutations in two genes, dubbed BRCA1 and BRCA2, that dramatically increase a woman's risk of breast and ovarian cancer. A woman without a mutation has a 13 percent chance of developing breast cancer and a 1.7 percent chance of developing ovarian cancer; with one or more mutations, the risk jumps to between 36 percent and 85 percent for breast cancer and between 16 percent and 60 percent for ovarian cancer.

Women with BRCA mutations also tend to develop cancers at a young age.

In the United States, fewer than one in 100 people has a BRCA mutation. But among Ashkenazi Jews, as Jews of Eastern European ancestry are known, the rate is one in 40.

There are many ways BRCA1 and 2 can mutate, but three mutations are particularly common among the Ashkenazi. These are known as founder mutations, because each is believed to be inherited from a single common ancestor.

Other BRCA founder mutations have been identified in similarly insular populations, such as those in Iceland and parts of the Netherlands and Sweden.

A full BRCA screening costs $3,000, but Jewish women can get a $600 ''Ashkenazi screen,'' which looks only for the three Ashkenazi founder mutations.

'Doctors' offices are filled with Jewish women who are coming in and saying, 'We want to know,' '' said Dr. Olufunmilayo Olopade, a University of Chicago cancer geneticist.


Black women, in contrast, have a much broader range of overall genetic variation and more variation in their BRCA genes, according to a study Olopade published last year in the Journal of the American Medical Association. This has prevented a simplified BRCA test for black women.

In the United States, black women are less likely than white women to get breast cancer. Yet among those who do develop the disease, black women are more likely to do so at a young age: In the United States, 32 percent of black breast cancer patients are diagnosed before 50, compared with 23 percent of white patients.

More than 80 percent of Bahamians are black. But because Bahamians have been far more geographically isolated than African-Americans, they likely have a narrower range of genetic variation, said Turnquest, one of three cancer doctors now working in the island chain.

'The indigenous Bahamians really only come from about 20 `superfamilies,' '' he said. ``You can trace lineages back based on islands, almost to specific individuals.''

There is no national cancer registry for the Bahamas, and there has been no big-picture analysis of breast cancer there, Turnquest said. But if Hurley finds founder mutations in one or more of the islands' large clans, geneticists could develop a ''Bahamian screen'' that would allow more women -- particularly those whose close relatives have had breast cancer -- to learn whether their genes put them at high risk.

''It would dramatically change the face of what we're doing,'' Turnquest said.


The presence of a BRCA mutation does not mean cancer is a given, and cancer can develop in the absence of a mutation.

But women known to carry high-risk genes can be screened earlier and more carefully for cancer. And women whose family history, genes and medical history put them at extremely high risk may choose to take radical preventive measures, such as taking strong drugs or having their breasts or ovaries surgically removed.

Williams -- who was diagnosed with cancer in one breast in 2001, then with cancer in her other breast in 2004 -- learned last year that she has a high-risk BRCA mutation. She plans to have her ovaries out this spring.

She is one of nine girls, and the fourth to get breast cancer. One sister died of the disease before her 40th birthday.

The others, like many high-risk women, don't want to be tested for BRCA mutations, according to Williams.

''They say they believe in God and they've healed and cancers aren't going into their body and that it just won't happen to them,'' she said.

Williams has other plans for her 4-year-old daughter, the baby she was pregnant with when she noticed the lump in her breast.

''When she reaches the age, I definitely will take her to do the genetic testing,'' she said.

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