Pharmacogenetics research enters second phase

By B.L. Azure
THHS
Public Information Officer

University of Montana Pharmacy School professors, Dr. Liz Putnam and Dr. Erica Woodahl, along with Dr. LeeAnna Muzquiz and Kevin Howlett of Tribal Health and Human Services discuss the pharmacogenetics research project with the Tribal Council. (B.L. Azure photo)

ST. IGNATIUS — The Confederated Salish and Kootenai Tribes Tribal Health and Human Services Department has been involved in a cutting edge cancer research project since 2007. The research based in the field of pharmacogenetics seeks to determine how and why some people — American Indians in this case and Salish, Pend d’Oreille and Kootenai tribal people in particular — respond differently or have adverse reactions to cancer treatments due to their genetic makeup.

Tribal Health in conjunction with the University of Montana Department of Biomedical and Pharmaceutical Sciences and the Montana Cancer Institute Foundation — with the actions taken by the Tribal Council — entered into the community-based participatory research project in 2007. The Mayo Clinic and the University of Washington are also involved in the project, as are Alaska Native people.

In 2009, the group applied for and was awarded a $1.4 million research grant funded by the National Institute of Health to conduct pharmacogenetics research among American Indian and Alaska Native communities.

The grant is part of a larger NIH effort called the Pharmacogenomics Research Network. University of Montana researchers, collaborating with several other leading researchers from Northwest universities and tribal communities in Alaska and Montana, are building their research center as a part of this national network.

Tribal Health employees and members of the Community Pharmacogenetics Advisory Committee got hands on experience on genetics at a workshop at the Polson THHS Clinic awhile back. (B.L. Azure photo)

It is a well-known scientific fact the people can respond in different ways to the same drug — genetic makeup is a determining factor. Response to pharmaceuticals runs the gamut from no response to serious side effects. Somewhere along that continuum may be the perfect dose or there may be the need for a different pharmaceutical. A goal of the research project is to find that sweet spot where various types of cancer treatment pharmaceuticals are most effective.

Another goal is to provide culturally sensitive genetics instruction to American Indians to increase their awareness of genetics as a topic. This would include an understanding of genetics research and testing and careers in the field of genetics. As an overall goal, it was designed to help improve informed decision making about genetics and genetics research in Native American communities.

More than 400 Salish, Pend d’Oreille and Kootenai people participated in the first phase of the research project. During that portion researchers, among other things, collected blood samples at powwows, job fairs, health fairs and clinics on the Flathead Indian Reservation.

Initial genetic analysis has been done on those samples to see what if any patterns emerge that are specific to Salish, Pend d’Oreille people. According to the findings there were some genetic patterns that were different from the non-Indian people. The research results provided the basis for two professional papers the UM researchers want to publish in medical and scientific professional journals.

Three weeks ago (Feb. 7) Tribal Health and Human Services Director Kevin Howlett and THHS Medical Director Dr. LeeAnna Muzquiz, MD, and University of Montana Department of Biomedical and Pharmaceutical Sciences professors/researchers Dr. Erica Woodahl and Dr. Liz Putnam met with the Tribal Council to discuss the findings of phase 1 of the research project and get approval from them to publish the two research papers. The Tribal Council voted unanimously for publication of the papers.

One is entitled “Pharmacogenetics in American Indian Population: Analysis of CYP2D6, CYP3A4, CYP3A5 and CYP2C9 in the Confederated Salish and Kootenai Tribes” and was written by Dr. Erica Woodahl, Ph.D., University of Montana Department of Biomedical and Pharmaceutical Sciences.

The goal of the study was to estimate how often genetic changes occur among Salish, Pend d’Oreille and Kootenai tribal people and compare that to what is known about other ethnic groups to better understand how they may process cancer pharmaceuticals differently. Researchers evaluated 140 distinct genetic changes in four genes in the DNA that are involved in response to the cancer drug tamoxifen. The four genes make proteins in the liver that are important for processing and eliminating drugs from the body. Changes in the genes can effect how efficiently the body can process a drug.

“These results highlight the value of pharmacogenetics research in Salish, Pend d’Oreille and Kootenai people,” Woodahl said. “Pharmacogenetic studies from other populations cannot always be applied to American Indian populations.”

The other research paper, “Pharmacogenetics for Cancer Chemotherapy in the Confederated Salish and Kootenai Tribes” was authored by University of Montana Department of Biomedical and Pharmaceutical Sciences professor Dr. Mark Pershouse, Ph. D.

The study focused on the benefits and risks of using cancer chemotherapy drugs for treatment of Salish, Pend d’Oreille and Kootenai people. Researchers looked at 17 locations in the DNA that can predict how drugs would act in an individual. In comparison with research on European populations the researchers found many location similarities but also found a few where the locations in the DNA among the Flathead Reservation tribal people were different. As a result researchers have surmised that some cancer treatment drugs would work differently in Salish, Pend d’Oreille and Kootenai people.

“We found that people we studied were unique,” Putnam said. “This information could help the doctors treating Salish, Pend d’Oreille and Kootenai people to make the best choice of medicine for each individual patient.”

The Tribal Council also gave the go ahead for the second phase of the research. A portion of the second phase is to recruit volunteers to participate in focus groups. Approximately six months ago the researchers conducted a mock focal group session with members of the Community Pharmacogenetics Advisory Council at the University of Montana. The resulting information will help guide researchers in a culturally sensitive manner when questioning focus group volunteers.

The focus group must be comprised of members of the Confederated Salish, Kootenai and Pend d’Oreille Tribes who are 18 years old or older. The identities of the focus group volunteers will remain confidential.

The researchers also received permission to further research the clinical effect of a genetic change in a liver enzyme that was found to appear more often in the Salish, Kootenai and Pend d’Oreille population than in Europeans. That would require the recruitment of volunteers but that will not happen until the UM Institutional Review Board approves the study.

“Today cancer is about the worst enemy we have. We can’t seem to get a handle on it,” said CPAC member Tony Incashola awhile back. “What is being done here is very important. We need to try and understand how genetics affect efforts to find cures for ailments and diseases. We want to give our future generations a better chance in life.”

Tribal Health and Human Services Director Kevin Howlett and THHS Family Physician and Medical Director Dr. LeeAnna Muzquiz, M.D. are the THHS administrative and medical liaisons in the research study.

Dr. Patrick Beatty, M.D., Ph. D., president of the Montana Cancer Institute Foundation and oncologist with the Montana Cancer Specialists located at St. Patrick Hospital, and Cindi Laukes, M.A., Clinical Research Manager at the Montana Cancer Institute Foundation are also a part of the research project.

The UM researchers include professors: Dr. Erica Woodahl, Ph.D.; Dr. Mark Pershouse, Ph.D.; and Dr. Liz Putnam, Ph.D.

UM Pharmacy School graduate school student in Pharmaceutical Sciences Chelsea Morales, of the White Clay (Gros Ventre) Nation of Fort Belknap, is also working on the project.