Hablando de Genética

Education initiatives and easier access to genetic testing in the Latino community is helping untangle disease risk.

By Charlotte Huff featured image Illustration by Federico Jordan

Gabino Cerda knew that there was an unsettling pattern of colon cancer in his family when two older siblings were diagnosed, and not long after, he too was diagnosed, at age 41. Cerda believed that diet and other lifestyle habits were solely to blame until he attended a presentation about genetic testing at a veteran’s program in Laredo, Texas.

“It never crossed my mind that it was in the genes,” says Cerda, now 44 and the father of three children, ages 8 to 20. When Cerda learned that his kids might also be vulnerable, he jumped at the opportunity to get tested for Lynch syndrome.

The results came back negative for the related mutations — found in genes such as MLH1, MSH2, and MSH6 — which are linked to colon, stomach, and other cancers. “I’m very relieved,” he says. “My main concern is my family.”

The presentation that Cerda heard is part of an ongoing grant-funded outreach initiative along the South Texas border called GRACIAS Texas, short for Genetic Risk Assessment for Cancer In All South Texas. It’s one of a growing number of national efforts to educate Hispanics about the genetic underpinnings of disease and to provide easier access to testing.

Hispanics, also referred to as Latinos, comprised nearly 18 percent of the U.S. population by 2015, up from 9 percent in 1990, according to Census Bureau data. Despite efforts to diversify genetic research participation across all ancestral groups, just half of 1 percent of the genetic samples worldwide come from individuals who identify as Hispanic/Latino, according to a 2016 analysis of 2,511 genome-wide association studies published in the journal Nature.

Identifying ancestral genomic information — insights that can assist with everything from deciphering disease risk to tailoring drug dosages — is infeasible without a sufficient sample size, says Esteban González Burchard, a pulmonologist and genetics researcher at the University of California, San Francisco. “We don’t know what we’re missing,” he says.

Moreover, the shortfall potentially harms more than just Hispanics in a diverse country like the U.S., according to Burchard and other genetic researchers and counselors. The umbrella demographic term of “Hispanic” refers to individuals who frequently have a mix of European, African, and American Indian heritages. (Some prefer the term “Latino,” pointing out that “Hispanic” refers to those who are Spanish-speaking and thus leaves out, for instance, Brazilians who speak Portuguese.) Africans represent just 3 percent of the genetic samples worldwide and indigenous peoples less than 0.50 percent, according to the same Nature analysis.

Efforts are accelerating to boost diversity in the genetics pool, with studies such as the ongoing Hispanic Community Health Study/Study of Latinos, along with the ambitions of the U.S. Precision Medicine Initiative. A major component of the initiative is the National Institutes of Health research program called All of Us that’s designed to build an environmental, behavioral, clinical, and genetic database from at least one million volunteers representing the diversity of the U.S. population.

Perhaps the greatest challenge is reaching first-generation immigrants, who might be primarily Spanish speaking, as well as needing medical care, due to lack of insurance or the logistics of juggling two or more jobs, says Ana Morales, a genetic counselor and an associate professor at Ohio State University in Columbus. A 2015 survey conducted by the Centers for Disease Control and Prevention found that nearly 22 percent of people under the age of 65 who identify as Hispanic in the U.S. do not have health insurance.

Cultural or religious beliefs also can be influential, Morales says. She previously worked in the Miami area, where she was involved with prenatal genetic counseling, including the option to get bloodwork to detect genetic or chromosomal disorders. “Some patients would say that [such testing] would be interfering with God’s will,” she recalls.

The Clinical Case

In the U.S., nearly two-thirds of those classified as Hispanic are originally from Mexico, according to the Census Bureau. But Mexicans are by no means a homogeneous genetic group, according to an analysis published in 2014 in the journal Science. The authors studied genetic variants from slightly more than 1,000 Mexicans and found that some people living in different regions of the country could differ from each other genetically to the same degree that Europeans differ from East Asians.

Moreover, such variances might affect medical care, says Burchard, a co-author. Take lung function, a scenario analyzed in the Science paper. Lung function test results used to diagnose asthma and other lung diseases were found to vary significantly among Mexicans, depending upon whether they lived in regions of the country with either a low or high percentage of people of American Indian ancestry.

If a Mexican patient’s lung function thresholds aren’t compared against those of other patients from a similar mix of ancestries, there’s the potential for misdiagnosis in the case of diseases like asthma, Burchard says.

In another emerging area of research, insights into the development of breast cancer might one day also benefit individuals who don’t necessarily classify themselves as Hispanic on a census form. Broadly speaking, Hispanics are less vulnerable to developing cancer than non-Hispanic whites. Hispanics have lower rates of common malignancies such as breast, colon, and lung cancer, according to an analysis of data published in 2015. (However, some less common types of cancer are more frequently diagnosed in Hispanics, including liver and stomach.) Better lifestyle habits are partly responsible; smoking rates, for example, are lower among Hispanics.

But there are genetic elements as well. For instance, breast cancer is less likely to be diagnosed in Hispanic women with significant American Indian ancestry com-pared with those whose heritage is more strongly European.

A 2014 study points to one contributor: a variant in Hispanic women that originates from American Indians. Those who carry at least one copy of the variant — roughly 20 percent of U.S. Latinos — are 40 percent less likely to be diagnosed with breast cancer, according to the researchers.

The next step is to discover how that variant, or other variants correlated with it, helps protect against breast malignancies, with the hope of eventually incorporating that mechanism into a drug, says Laura Fejerman, a researcher on that study and an associate professor of medicine at the University of California, San Francisco. “And that drug wouldn’t be just for Latinas, right?” she points out. “It would be for anyone.”

In other work, researchers are studying why Hispanic children with a common form of leukemia are more likely to relapse, as well as why some are more prone to suffering toxic effects from drug treatment.

Researchers have learned that children with at least 10 percent Native American ancestry — particularly those with the GATA3 gene variant — are more vulnerable to relapse after treatment for acute lymphoblastic leukemia (ALL). By analyzing data from a randomized clinical trial, they also determined that adding another course of drug treatment effectively guarded against that relapse, says Jun Yang, one of the researchers and also an associate professor in the department of pharmaceutical sciences at St. Jude Children’s Research Hospital in Memphis, Tennessee.

More recently, researchers at St. Jude have discovered a genetic link, a variant in the NUDT15 gene, in children who experience a serious toxic reaction to a class of cancer drugs called thiopurines, which are vital to treating ALL. Children with that variant are extremely vulnerable to suffering toxic effects and can tolerate no more than one-tenth of the typical dose, according to a 2016 study in Nature Genetics.

That variant is most commonly found in children of East Asian ancestry, followed by Hispanics, but is almost nonexistent in whites and blacks, Yang says. Recently, clinicians at St. Jude have begun testing all children for the NUDT15 variant before they get any thiopurine treatment, and adjusting the dosing if needed. Before the variant was identified, Yang says, “there was no way of predicting who was going to have toxicity and who was not. We would give everybody the same dose.”

Reaching Out

But if they don’t know about genetic testing in the first place, says Morales, the genetic counselor at Ohio State, Hispanics can’t consider their options. What if, she asks, a patient’s very high cholesterol reading is detected at a busy primary care clinic, and with it the possibility of the inheritable disorder of familial hypercholesterolemia? “Is the idea of getting referred [for testing] even presented to them in the first place?”

Another barrier is the fact that bilingual counselors such as Morales are a rarity, Burchard says. He also worries that other influences, such as the recent crackdown on illegal immigration, will discourage patients from seeking out medical care altogether.

Along the Texas border with Mexico, it’s believed that there are few, perhaps even no, genetic counselors. This was the impetus behind launching the GRACIAS Texas program, says Anna María Pulido-Saldívar, a bilingual health educator who works in the Laredo office for the genetic outreach initiative. The ongoing effort, funded by a grant from the Cancer Prevention & Research Institute of Texas, also uses videoconferencing to help patients communicate with a genetic counselor in San Antonio. (See “Counseling Via Video?” left.)

Pulido-Saldívar has talked about testing at health fairs and churches, among other locations, working to counter misconceptions along the way. For example, someone might think that genetic testing isn’t needed because they’ve already had cancer. Or they might question messing with destiny or fate. De algo nos vamos a morir — “We’re all going to die of something”— is a common expression in Spanish, Pulido-Saldívar says.

Although she never pressures people, because testing is a highly personal decision, when Pulido-Saldívar hears this fatalistic sentiment, she tries to drill down further. Of course we’re all going to die of something, she says, but why not later rather than sooner?

Cerda says that he’ll advise his children, once they become adults, to take advantage of the genetic insights they can gain into their own cancer vulnerability. Even though he developed colon cancer in his early 40s, he says, “It never crossed my mind about genetics.”