Department of Translational and Applied Genomics (TAG)

Dementia, including Alzheimer’s disease (AD) and related disorders, is a progressive condition with growing prevalence due to the aging of the population. AD accounts for about 60% of dementia cases and has a high estimated genetic heritability. The apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor accounting for up to 9% of dementia cases, and is an important factor considered in recruitment and treatment strategies for clinical trials of newly emerging therapies to slow cognitive decline. However, the majority of studies on the genetics of AD and dementia are limited to European genetic ancestry populations. The Kaiser Permanente Research Bank (KPRB) and high-resolution genetic ancestry data can help address the critical lack of large-scale ethnically diverse studies in AD and related dementias research. Therefore, we propose leveraging KPRB genetic, survey, and electronic health record (EHR) data to comprehensively evaluate APOE genotype and associated dementia risk by genetic ancestry, with a focus on expanding research to non-European populations.

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Willa Brenowitz
Willa.D.Brenowitz@kpchr.org

The CARE-HCS study will compare the effectiveness of two outreach approaches to usual care for patients with hereditary cancer syndromes (HCS). We wish to understand how different ways of providing information to patients with an increased genetic risk for cancer may affect their completion of recommended cancer screening tests. The first type of outreach (low-touch intervention) is an annual educational letter sent via patient portal and/or mail. The second type of outreach (high-touch intervention) is a phone call by a study care coordinator to discuss genetic risk management guidelines. Participants will receive outreach from the study for 2 years. The study will also examine the acceptability and sustainability of these outreach methods using qualitative interviews with patients and health system representatives.

CARE-HCS is being conducted at KPNW and Denver Health with the intention of providing guidance to health care system decision makers about the standard of care for patients with HCS.

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Sacha Reich
Sacha.L.Reich@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

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; Sheila Weinmann is the CHR Site PI.

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Sheila 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

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

Sheila 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

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.

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Shelia Weinmann
Sheila.Weinmann@kpchr.org