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Your Environment. Your Health.

Studying Diverse Populations to Understand Arsenic’s Impact on Health

Ana Navas-Acien, M.D., Ph.D.

October 3, 2018

Navas-Acien, M.D., Ph.D.

Navas-Acien was named director of the Columbia University Superfund Research Program (SRP) in January 2018. She is also the co-founder and co-editor-in-chief of Current Environmental Health Reports, a review journal that gives researchers a platform to discuss and reflect on developments in their field.
(Photo courtesy of Ana Navas-Acien, M.D., Ph.D.)

NIEHS grantee Ana Navas-Acien, M.D., Ph.D., is a physician-epidemiologist studying the health effects of metals and other harmful elements. Exposure to arsenic, a naturally occurring element, has been associated with long-term health impacts, including heart and respiratory diseases, diabetes, and some forms of cancer. By investigating the role that genetics and other exposures play in arsenic-induced diseases, Navas-Acien hopes to develop interventions that will improve health outcomes in vulnerable groups.

One gene that Navas-Acien studies related to arsenic exposure and disease susceptibility is arsenite methyltransferase. This gene helps the body metabolize arsenic through a chemical process called methylation. If the body cannot properly methylate arsenic, it could potentially lead to negative health effects.

She is also exploring epigenetics, or heritable changes that affect gene expression without changing the genetic sequence in DNA, and how this can play a role in arsenic-induced disease in various ethnic groups. “We know that arsenic exposure can lead to epigenetic changes, but little is known about how these changes contribute to disease development,” said Navas-Acien.

Investigating arsenic exposure and heart disease in Native populations

Navas-Acien is also a co-investigator for the Trial to Assess Chelation Therapy 2 (TACT2), a clinical trial co-funded by NIEHS which seeks to prevent recurring cardiac events in diabetic patients. She leads the biorespository working group for TACT2, which is involved in collecting biospecimens and measuring levels of metal exposure in participants. This trial will provide novel insight into how chelation, a treatment to remove heavy metals from blood, can impact heart disease outcomes among diabetics.

A significant portion of Navas-Acien’s research efforts are dedicated to the Strong Heart Study (SHS), a multi-phase cohort study that investigates underlying causes and risk factors associated with the disproportionate level of heart disease found in Native American populations living in Oklahoma, North and South Dakota, and Arizona.

Originally, SHS focused on traditional risk factors for heart disease, such as lifestyle and diet. However, Navas-Acien and colleagues have expanded their research to explore possible connections between environmental exposure to arsenic and disease. In an ongoing study, they found that drinking water in over 25 percent of homes in two primarily Native American communities contained levels of arsenic over the regulatory safety standard. In other SHS studies, Navas-Acien and her colleagues have connected exposure to arsenic in low to moderate concentrations with adverse health outcomes. In one such study, they found an association between low to moderate levels of arsenic exposure and heart disease incidence and mortality.

SHS group

SHS is the largest epidemiologic study of cardiovascular disease in Native Americans, it began in 1988 after a taskforce on Minority Health concluded that there was insufficient research on Native populations and cardiovascular disease.
(Photo courtesy of Ana Navas-Acien, M.D., Ph.D.)

Another study determined associations between arsenic methylation, which can be dependent on genetics and diet, and the development of diabetes and metabolic syndrome, which is common in Native Americans. Navas-Acien and colleagues hope by understanding the dose-response relationship between arsenic and disease, that they will be able to inform regulations for safe drinking water and reduce the burden of disease in these communities.

Returning benefits of research to the community

Recognizing the urgent need for interventions to reduce arsenic exposure among SHS participants, Navas-Acien began working closely with Columbia University Superfund Research Program alumna Christine George, Ph.D., and colleagues at Missouri Breaks Industries and Research Inc. to study the impact of various interventions. In an ongoing study of 300 Native American households in North and South Dakota, they are testing the effectiveness of interventions, including well-testing, arsenic removal, and home-visits from health promotion specialists.

This study will be the first to develop and evaluate a multi-level intervention to reduce arsenic exposure in Native American communities. Navas-Acien feels that after learning about the adverse health effects of metal exposure, she and other researchers have a responsibility to help the communities benefit from the research. “I think this was a natural next step in my research. If we spend the time to find the impacts, then we should also spend the time to prevent them,” stated Navas-Acien.

Translating findings across populations

sink with faucet and filter

This image shows a filter similar to the ones being installed by Navas-Acien and George’s SHS team in Native American homes to reduce exposure to arsenic in drinking water.
(Photo courtesy of Strong Heart Water Study, presented to the National Cancer Institute)

In January 2018, Navas-Acien was named director of the Columbia University Superfund Research Program (SRP). For many years, the Columbia SRP program was led by Joseph Graziano, Ph.D. Navas-Acien is excited to continue his mission to fully understand the health effects of metals exposure. To this end, Columbia SRP’s Health Effects from Arsenic Longitudinal Study (HEALS), directed by Habibul Ahsan, M.D., explores the health impacts from arsenic in drinking water.

HEALS uses health and exposure data collected from over 35,000 study participants in rural Bangladesh starting in 2000. In work directed by Mary Gamble, a colleague from Columbia University SRP, Navas-Acien and her colleagues have found evidence that nutrition and arsenic exposure may lead to arsenic-related skin lesions in people with certain genetic sequences. The HEALS team is more broadly studying how genetic sequences may predispose individuals to various arsenic-related health outcomes and if findings can be translated across populations.

HEALS is unique among other SRP cohorts, as it draws its data from an international population and focuses on non-cancer health outcomes. Navas-Acien hopes that the foundation of primary research being collected by the HEALS cohort can be used to cross-examine other populations being studied for arsenic exposure, including SHS and the Multi-Ethnic Study of Atherosclerosis (MESA). MESA will examine the relationship between ethnic background and arsenic exposure in multi-ethnic adult populations across the U.S. Navas-Acien and the Columbia SRP Trace Metals Laboratory will measure arsenic exposure in about 6,000 U.S. adults to better understand this potential relationship.

Long-term, Navas-Acien hopes that cross-investigation can help researchers understand common themes in disease development. “As HEALS and other studies begin to collaborate more, we can identify the generalizable mechanisms of disease and develop interventions for broader populations,” said Navas-Acien.

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