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December 23, 2009 – Marc Silver
Minorities and Cancer: A Lesson for Us All
December 23, 2009 – Debu Tripathy, MD
Completing the Circle of Life
December 23, 2009 – Kathy LaTour
Highlights
December 23, 2009 – Kathy LaTour
Cancer Heroes
December 23, 2009 – Marc Silver
The Many Shades of Survivorship
December 23, 2009 – Kathy LaTour
A Personal Guide
December 22, 2009 – Karen Patterson
Race, Genetics & Cancer
December 23, 2009 – Karen Patterson
Cultural Connections
December 23, 2009 – Marc Silver
Minorities and Cancer: A Lesson for Us All
December 23, 2009 – Debu Tripathy, MD
Completing the Circle of Life
December 23, 2009 – Kathy LaTour
Highlights
December 23, 2009 – Kathy LaTour
Cancer Heroes
December 23, 2009 – Marc Silver
The Many Shades of Survivorship
December 23, 2009 – Kathy LaTour
A Personal Guide
December 22, 2009 – Karen Patterson
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Race, Genetics & Cancer
December 23, 2009 – Karen Patterson

Race, Genetics & Cancer

What role does race and ethnicity play in cancer?

BY Karen Patterson
PUBLISHED December 23, 2009

At age 35, Carey Weiner was about to get tested to see whether she had a form of a gene that would put her at greater risk for breast cancer. But before Weiner, of Wellington, Florida, could get the test, she found out the risk was a reality: she had ductal carcinoma in situ—cancer contained within the ducts of the breast. Weiner, who is of Ashkenazi Jewish descent, had known her risk could be high. Her maternal grandmother died from breast cancer, and her mother and aunt tested positive for the genetic variant—a mutation in a gene called BRCA1. But Weiner’s gynecologist told her, in error, that she was too young to worry about it.

In September 2007, Weiner underwent a bilateral mastectomy and learned that she, too, had the BRCA1 mutation. In 2008, she had a total hysterectomy, including removal of her ovaries, to protect herself from another threat posed by BRCA1: ovarian cancer.

Genetic mutations linked to specific cancers can affect certain racial or ethnic groups more than others. For instance, the same BRCA1 mutation, which is more common in Ashkenazi Jews than in the population as a whole, also appears to be somewhat more common in Latinas. Meanwhile, mutations in another breast cancer-related gene, BRCA2, are slightly more frequent among African-Americans, putting them at higher risk of very aggressive breast and ovarian cancers compared with white women, according to the National Cancer Institute. (Women of any racial or ethnic group with a family history of breast cancer, or with relatives known to have mutations in the BRCA1 or BRCA2 genes, should discuss the possibility of testing with a genetic counselor.)

For African-American men, several genetic factors tied to prostate cancer have been reported, the NCI says. Specifically,­ recent research has found different combinations of genetic variants associated with higher or lower prostate cancer risk—and the bulk of those linked to higher risk were found most often in African-Americans.

Another example involves Asians. Recent evidence suggests a particular genetic variant, which affects alcohol metabolism, increases liver cancer risk, and that this variant is most common in people living in southeast China.

Other discoveries relate to how the body metabolizes drugs or other substances that can affect the vitality of a tumor.

“Genetic factors can impact how a tumor progresses and how it will react to various treatments,” says Sanya Springfield, PhD, director of the NCI’s Center to Reduce Cancer Health Disparities. “Some ethnic groups may experience greater toxicity when treated with the same dose and schedule of drugs. In other words, based on your genetic differences, a person may react differently to different drugs. This is because of gene variations in drug-metabolizing enzymes.” 

For instance, a variant of a gene called CYP2D6, found more often in Asians, may result in poor metabolism of the breast cancer treatment tamoxifen. Because the drug is not converted to its more active form, the medicine could be rendered less effective and other treatments might be better choices.

Research is also beginning to sort out how race or ethnicity is linked to biological differences in tumors themselves.

One example involves a gene mutation that is not inherited, but develops in the cells of various cancers, including lung cancer. The gene, known as epidermal growth factor receptor, or EGFR, can be exploited by targeted treatments. Some recent studies analyzing EGFR mutations suggest they occur at a much higher level in Asian patients than in non-Asian patients. In addition, evidence suggests that Asians’ response to lung cancer treatments targeting EGFR is better than non-Asians’ response.

“Rather than attribute the disparity in cancer survival only to the real problems of poverty or poor access to care, we think these data tell us there’s something additional going on in the sex-specific cancers.”

Such evidence includes a 2005 study of the EGFR-targeting treatment Tarceva (erlotinib) in non-small cell lung cancer patients who had received prior treatment. That study, published in The New England Journal of Medicine, found that of the 427 patients on Tarceva, 38 of them—or 8.9 percent—had their tumors shrink by at least one-third. But in Asians, that percentage more than doubles. Of the 53 Asian patients receiving Tarceva, 10 individuals—or 18.9 percent—experienced tumor shrinkage of at least one-third, the study found.

Other recent research has shed light on whether any inherent biological differences in cancers and their environment contribute to shorter survival time among African-Americans compared with Caucasians. That study, led by Kathy Albain, MD, breast and lung cancer specialist at Loyola University Chicago’s Cardinal Bernardin Cancer Center in Maywood, Illinois, examined survival for a variety of cancers in African-Americans and Caucasians when various factors were made equal—that is, people at the same stages of treatment who had received identical treatment from the same set of doctors.

The study, examining records from almost 20,000 patients, also adjusted for factors known to influence the outcomes of a particular cancer—for instance, number of lymph nodes involved in early-stage premenopausal and postmenopausal breast cancer. Other cancer types studied were early-stage colon cancer; acute myelogenous leukemia; limited-stage small cell lung cancer; advanced non-Hodgkin lymphoma; advanced prostate, non-small cell lung, and ovarian cancers; and multiple myeloma. The researchers also adjusted for socioeconomic status, likewise an important influence on outcome, Albain says.

For the majority of cancers studied, there was no significant difference in survival time. In other words, Albain says, all things being equal, if African-Americans go to good doctors and get good treatment, “they will do just as well in most common cancers.”

The exceptions were the sex-specific cancers—breast, ovarian, and prostate. Looking more closely at these cancers, researchers accounted for other potentially relevant factors, including obesity. But the survival difference persisted.

For breast cancer, the researchers separated out patients with estrogen receptor-negative cancers, which disproportionately affect African-Americans, and focused on just estrogen receptor-positive cancers. “There still was a disparity,” Albain says. That disparity in breast cancer held even when researchers adjusted for white blood cell counts, a reflection of the ability to receive full doses of treatment, and adherence to medical ­appointments.

“Rather than attribute the disparity in cancer survival only to the real problems of poverty or poor access to care, we think these data tell us there’s something additional going on in the sex-specific cancers,” Albain says. “We’re picturing a possible interaction between what you as an individual inherit that activates and metabolizes your hormones and chemotherapy drugs, and also the tumor’s own biology.”

None of this diminishes the role played by social and cultural factors, such as poverty and lack of access to health care, problems that can affect minority groups disproportionately. For instance, poor access to care has been found to lead to diagnostic and treatment delays that can worsen a cancer patient’s prognosis.

From a societal viewpoint, simply associating certain cancer outcomes with race or ethnicity can divert attention from such underlying causes of cancer health disparities, says Otis Brawley, MD, chief medical officer of the American Cancer Society. “It may very well be race causing socioeconomics to be such that … black women are overwhelmingly poorer compared to white women, and that very well may be much of the answer” behind differences in cancer outcomes, he says.

While Albain’s study shows that equal treatment leads to equal outcomes for most of the cancers, says Brawley, “we have data that show there is not equal treatment in the United States.”

From a biological perspective, Albain notes that inherited patterns of drug and hormone activation and metabolism, while often highly connected with specific racial or ethnic groups, don’t track with race or ethnicity per se.  

“Race is a proxy for inherited traits,” she says. “There are going to be Caucasians that have that same profile, whatever it ends up to be.” Once such profiles are understood, she says, doctors will be able to provide highly personalized treatment, based on the specific gene patterns patients inherit, rather than broader racial or ethnic classifications. 

—Kathy LaTour contributed reporting.

“Race is a proxy for inherited traits. There are going to be Caucasians that have that same profile, whatever it ends up to be.”

Weiner, now 37, says it’s troubling to grasp that a part of her identity—her Ashkenazi heritage—is linked to a higher risk of cancer. 

“We kind of have been gypped,” she says. “There are so many health problems with Jewish people ... that they have to look for in genetics. And now here’s another thing.

“But at least they now know there is something out there to look for; there is that BRCA test,” Weiner says.

Knowledge about links between ancestry and cancer risk is growing—and with it, the possibilities of tailoring screening and prevention efforts to specific populations, and targeting treatments to particular genetic characteristics of a tumor or a patient.

Knowledge about links between ancestry and cancer risk is growing—and with it, the possibilities of tailoring screening and prevention efforts to specific populations, and targeting treatments to particular genetic characteristics of a tumor or a patient.

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