Department of Translational and Applied Genomics (TAG)

The CHARM (Cancer Health Assessments Reaching Many) study assessed the utility of clinical exome sequencing and how it affects care in diverse populations. Our study population included adults at risk for hereditary cancer syndromes. The primary objective was to implement a hereditary cancer risk assessment program in healthy 18-49 year-olds in primary care settings within a vertically integrated health delivery system (Kaiser Permanente) and a federal qualified health center (Denver Health). We assessed clinical exome sequencing implementation and interpretation, as well as tailored interactions for low health literacy including a contextualized consent process, and a modified approach to results disclosure and genetic counseling. We also assessed the clinical utility (healthcare utilization and adherence to recommended care) and personal utility of primary and additional results from clinical exome sequencing and evaluated the ethical and policy implications of considering personal utility of genomic information decisions for health care coverage.

Quicklinks

Study Website
CHARM Newsletter

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Michael Leo
Michael.C.Leo@kpchr.org

ClinGen is a National Institutes of Health (NIH)-funded resource that represents a collaborative effort by the genetics community to provide an evidence-based source for the assessment of the clinical relevance of genes and variants for use in precision medicine and research. The ClinGen Consortium consists of multiple grants and has over 2,300 contributors from more than 65 countries. The ClinGen program addresses many critical questions including: 1) Is this gene associated with a condition? 2) is this gene variant causative of disease? and 3) is this information actionable in the clinical setting? The KPNW team leads the Actionability Working Group which has the overarching goal of assessing the third critical question; whether a gene, when significantly altered, confers a high risk of serious disease that could be prevented or mitigated if the risk were known. In this context, clinical actionability is defined narrowly in terms of the availability of clinical interventions that effectively prevent or delay onset of genetic-linked conditions, reduce clinical burden, or improve health outcomes. The work group assesses actionability in two clinical contexts, Adults and Pediatrics. A framework to assess actionability for polygenic risk scores is being developed.

Quicklinks

Study Website

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Joanna Bulkley
Joanna.E.Bulkley@kpchr.org

The Connect for Cancer Prevention Study wants to better understand the causes of cancer and how to prevent it. Kaiser Permanente Northwest (KPNW) Center for Health Research is partnering with participating health care systems throughout the country to partner with the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), for Connect. The study will enroll up to 200,000 adults who get their health care from a partner health care system, are between 30-70 years old at enrollment, and have never had cancer. People who have or once had non-melanoma skin cancer, or a condition that raises the risk of getting cancer (such as DCIS, or stage 0 breast cancer), can still join.

Participants will be asked to answer online health surveys, donate samples of blood, urine, and saliva, and share access to their electronic health records. This information will help researchers study the health and behavior patterns that may affect cancer risk.

Quicklinks

Study Website
clinicaltrials.gov 

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Mark Schmidt
Mark.A.Schmidt@kpchr.org

The primary objective of this project is to identify potential germline susceptibility variants that determine host responses to COVID-19 infection that would allow improved patient stratification and identification of potential therapeutic targets to moderate the severe symptoms of the disease.

To accomplish this objective, we completed the following specific aims:

1. Identify within the Northwest Bio Bank (NWBB) cases of COVID-19 confirmed from laboratory testing and conduct a genome wide association study (GWAS) on COVID-19 cases. 225 cases were identified, and GWAS was performed on 224 of these.
2. Combine relevant medical record and NWBB data, in particular patient demographics, signs and symptoms, clinical course, comorbid conditions and vital status with GWAS data to understand the genetic determinants of COVID-19 infection and severity, understand the interaction with pre-existing conditions, and identify potential interventions to mediate the severity of disease and risk of death.

All samples were genotyped at the NCI Intramural Program (DCEG), the Cancer Genomics Research Laboratory (CGR), part of the Frederick National Lab using the Illumina GSA v2 array. Imputation was performed using the Michigan Server (targeting 66 million SNPs or more). Analysis led by NCI staff is underway.

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Shelia Weinmann
Sheila.Weinmann@kpchr.org

An estimated 15% of women diagnosed with ovarian cancer carry a gene change associated with an increased risk of cancer. Thus, guidelines released in 2019 recommend that all women with ovarian cancer should be offered genetic counseling and testing. However, women with a diagnosis of ovarian cancer before these recommendations were in place could also benefit from genetic risk information. The GRACE study will use a “traceback” approach to offer women and their families genetic testing to identify gene changes associated with a higher cancer risk. We will identify and contact women who were patients at KPNW or KPCO at the time of their ovarian cancer diagnosis who could benefit from genetic counseling and testing. We will begin with the patient’s tissue from their cancer surgery that is safely preserved and carefully cataloged. We will ask for permission to perform genetic testing on their tissue. Since we are using existing tissue samples, we can also offer genetic risk information to family members of women who have died. In these cases, we will contact family members listed in the medical record to ask for their permission to test the tissue. We will also conduct interviews with up to 20 family member contacts to assess their perspectives on the risks and benefits of genetic testing, and how they would prefer to be informed about genetic testing for a deceased family member. For women who have a gene change, we will offer genetic testing for her relatives (cascade testing). The GRACE study will give women and their family members important information about their cancer risk.

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Yolanda Prado
Yolanda.k.prado@kpchr.org

Screening tumors from all newly diagnosed cases of colorectal cancer for Lynch Syndrome (LS), an inherited cancer syndrome, has been recommended since 2009, but this screening remains variable across health care systems in the U.S. The Implementing Universal Lynch Syndrome Screening (IMPULSS) study, funded by NCI’s Cancer Moonshot Initiative, involves eight health care systems. The goal of this study is to describe and explain variation in Lynch syndrome screening across varying health care systems to identify which factors are important for implementing successful screening programs. The study will also create a toolkit to promote effective screening in diverse health systems. Our goal is to prevent the needless suffering of patients and their family members from preventable cancers, and to inform strategies to make the promise of precision medicine a reality.

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Jessica Ezzell Hunter
Jessica.E.Hunter@kpchr.org

The Kaiser Permanente Research Bank (KPRB) is the second largest biobank in the U.S. and one of the most diverse in terms of participants. A biobank stores biological samples that volunteers have shared for use in research. Eight KP regions from across the U.S. have recruited health plan members to join the KPRB, which contains blood and saliva samples, as well as patient data for over 350,000 individuals. When they join, participants agree to broad use of their data for health research, including their biospecimens, health record data, survey data, and genomic data.

The KPRB includes a general population of over 343,000 participants and two special populations: a cancer group with over 9000 participants, and a pregnancy group with over 25,000 participants. The KPRB enables researchers to discover and learn more about genes and proteins that impact a variety of diseases. It also enables researchers to study the usefulness of specific genomic tests and services in the real world. By linking patients’ genetic data to their health records, the KPRB is making it possible to carry out studies that will ultimately improve patient care.

Quicklinks

• Study Website for Researchers
• Research Bank Video - Journey of the Sample

Contacts

Shelia Weinmann
Sheila.Weinmann@kpchr.org

This study uses KPNW’s pathology specimens and associated clinical data to validate a commercial test for patients diagnosed with ductal carcinoma in situ (DCIS) of the breast. The goal of the test is to stratify patients into risk categories to help guide treatment choice.

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Shelia Weinmann
Sheila.Weinmann@kpchr.org

Starting in March 2018, Medicare implemented a policy that covers genome-scale sequencing for patients with recurrent and advanced cancer. The study will leverage the Virtual Data Warehouse across six Health Care Systems Research Network (HCSRN) sites to evaluate the consequences of Medicare's coverage of next-generation sequencing for patients with recurrent, relapsed, refractory, metastatic, or advanced stage III or stage IV cancer. This study is funded by the National Human Genome Research Institute. Chris Lu at Harvard Pilgrim is the Study PI; Jessica Ezzell Hunter is the CHR Site PI.

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Jessica Ezzell Hunter
Jessica.E.Hunter@kpchr.org 

This study is a collaboration between CHR and investigators at Albert Einstein College of Medicine. The goal is to develop tools to identify those breast cancers that are likely to spread (metastasize) so that they may be treated with chemotherapy, while avoiding unnecessary and toxic treatment for women with less dangerous cancers. Using clinical data and tumor tissue from breast cancer patients at KPNW who were diagnosed in the past (from 1980-2015), we will examine the risk of distant metastasis (cancer spreading to a new site) associated with specific new tumor markers, the TMEM score developed in earlier work, and combinations of these markers. We will also examine risk of distant metastasis associated with established markers and with the TMEM score in comparison to and in addition to the established markers.

Contact Us:

Shelia Weinmann
Sheila.Weinmann@kpchr.org