Deborah Goodman

Participant views on consent in cancer genetics research: preparing for the precision medicine era.

The Precision Medicine Initiative (PMI) has created considerable discussions about research participant issues including re-consent and how and when to incorporate the patient experience into clinical trials. Within the changing landscape of genetic and genomic research, the preferences of participants are lacking yet are needed to inform policy. With the growing use of biobanks intended to support studies, including the national research cohort proposed under the PMI, understanding participant preferences, including re-consent, is a pressing concern. The Participant Issues Project (PIP) addresses this gap, and here we present data on participant attitudes regarding re-consent and broad consent in research studies. PIP study participants came from the Northwest Cancer Genetics Registry and included cancer patients, relatives, and controls. Thirty telephone interviews were conducted and analyzed using content and thematic analysis. Results indicate that in some scenarios, re-consent is needed. Most participants agreed that re-consent was necessary when the study direction changed significantly or a child participant became an adult, but not if the genetic variant changed. Most participants’ willingness to participate in research would not be affected if the researcher or institution profited or if a broad consent form were used. Participants emphasized re-consent to provide information and control of the use of their data, now relevant for tailored treatment, while also prioritizing research as important. In the era of precision medicine, it is essential that policy makers consider participant preferences with regard to use of their materials and that participants understand genetic and genomic research and its harms and benefits as well as what broad consent entails, including privacy and re-identification risks.

De-identified genomic data sharing: the research participant perspective

Combining datasets into larger and separate datasets is becoming increasingly common, and personal identifiers are often removed in order to maintain participant anonymity. Views of research participants on the use of de-identified data in large research datasets are important for future projects, such as the Precision Medicine Initiative and Cancer Moonshot Initiative. This quantitative study set in the USA examines participant preferences and evaluates differences by demographics and cancer history. Study participants were recruited from the Northwest Cancer Genetics Registry and included cancer patients, their relatives, and controls. A secure online survey was administered to 450 participants. While the majority participants were not concerned about personal identification when participating in a genetic study using de-identified data, they expressed their concern that researchers protect their privacy and information. Most participants expressed a desire that their data should be available for as many research studies as possible, and in doing so, they would increase their chance of receiving personal health information. About 20% of participants felt that a link should not be maintained between the participant and their de-identified data. Reasons to maintain a link included an ability to return individual health results and an ability to support further research. Knowledge of participants’ attitudes regarding the use of data into a research repository and the maintenance of a link to de-identified data is critical to the success of recruitment into future genomic research projects.

The research participant perspective related to the conduct of genomic cohort studies: A systematic review of the quantitative literature

Observational genome-wide association studies require large sample sizes. Evaluating the interplay between genomic, environmental, and lifestyle factors can require even larger sample sizes. The All of Us Research Program will recruit 1 million participants to facilitate research on genomic, environmental, and lifestyle factors. Integrating participant preferences into the research process is a new paradigm and a necessary component of the All of Us Research Program. The purpose of the study is to summarize quantitative studies of participant preferences related to participation in observational genomic research studies, starting with consent through return of results. Integrating this information into the conduct of genomic studies may benefit participants, and improve participant satisfaction, recruitment, and retention. We conducted a systematic review of the literature regarding participant views related to reconsent and broad consent, use of de-identified data, contribution of data to a biorepository, risk of identification, return of individual genetic results, and motivation for participation in genomic studies. Twenty-three articles met our inclusion and exclusion criteria. Study results found that most participants support broad consent; however, significant differences related to reconsent preferences have been shown by gender and age. Most participants support the return of individual genomic results and do not feel it is necessary to maintain a link to their de-identified data. Reasons given for joining research studies varied by population source. These findings, in addition to the knowledge that participants are more accepting of broad informed consent methods when the rationale is explained, can assist in developing guidelines for future observational genomic research.

A comparison of views regarding the use of de-identified data

Data sharing of large genomic databases and biorepositories provides researchers adequately powered samples to advance the goals of precision medicine. Data sharing may also introduce, however, participant privacy concerns including possible reidentification. This study compares views of research participants, genetic researchers, and institutional review board (IRB) professionals regarding concerns about the use of de-identified data. An online survey was completed by cancer patients, their relatives, and controls from the Northwest Cancer Genetics Registry (n = 450) querying views about potential harms with the use of de-identified data. This was compared to our previous online national survey of human genetic researchers (n = 351) and IRB professionals (n = 208). Researchers were less likely to feel that participants would be personally identified or harmed from a study involving de-identified data or feel that a federal agency might compel researchers to disclose information about research participants. Compared to genetic researchers, IRB professionals and participants were significantly more likely to express that personal identification or harm was likely or that researchers might be forced to disclose information by a federal agency. An understanding of the differences in views regarding possible harm from the use of de-identified data between these three important stakeholder groups is necessary to move forward with genomic research.

Controversies among Cancer Registry Participants, Genomic Researchers, and Institutional Review Boards about Returning Participants’ Genomic Results

Objectives: Genomic information will increasingly be used to aid in the prevention, diagnosis, and treatment of disease. Several national initiatives are paving the way for this new reality, while also promoting new models of participant-engaged research. We compare the opinions of research participants in a cancer registry, human genetic researchers, and institutional review board (IRB) professionals about the return of individual-level genetic results (ROR). Methods: Online surveys were administered to participants in a cancer registry (n = 450) and overlapping questions were compared to our previous online national surveys of human genetic researchers (n = 351) and IRB professionals (n = 208). Results: The majority of respondents agreed that researchers have an obligation to return individual results when they would affect a participant’s health. While 77% of registry participants favored ROR if the researcher feels the participant might be interested in the results, only 30% of the IRB professionals and 25% of the genetic researchers agreed with this statement. Conclusions: Significant differences emerged between the stakeholder groups in several ROR scenarios. Policies that are acceptable to participants, researchers and IRBs, and that ensure human subject protections and facilitate research are needed.

Effective risk communication to promote behavioral change in patients at elevated risk for breast cancer based on the Health Belief Model

Modifiable factors associated with increased breast cancer risk include obesity, low physical activity levels, and alcohol consumption; however, few women at elevated breast cancer risk follow a risk‐ reducing lifestyle. In addition, although chemoprevention lowers risk by ~50% in high‐risk women, <1% of women aged 35‐79 years who were eligible for chemoprevention in 2010 actually took it. These disparities present a challenge and opportunity for healthcare providers to improve their approach toward encouraging behavioral changes that will improve breast health. Application of the Health Belief Model (HBM) may provide insight into guiding such improvements. The HBM is a theory of health behavior that focuses on factors within the individual that influence behavioral change and is based on the assertion that health‐seeking behavior is influenced by ones perception of a threat and the value associated with actions aimed at reducing that threat. In this commentary, the HBM will be applied to breast cancer risk, with the goal of improving communication and promotion of healthy lifestyle changes. Each component of the HBM, relevance to breast cancer risk, and potential applications for effective communication are summarized in Table 1. The HBM predicts that higher perceived threat leads to higher likelihood of engagement in health‐promoting behaviors. A womans perceived threat of breast cancer is derived from a combination of her perceived susceptibility and severity of developing the disease. A recent study showed that as perceived threat increased, so did willingness to undergo invasive procedures. For example, when asked

Association of physical activity and sitting time with incident colorectal cancer in postmenopausal women

Findings from epidemiological studies have found that physical activity (PA) is associated with a lower risk of colorectal cancer (CRC). Recent studies have found an increased CRC risk with higher sitting time (ST); however, many studies did not include PA as a potential confounder. The objective of this project was to investigate the independent and combined associations of ST and PA with the risk of incident CRC, specifically colon and rectal cancer. Participants in the Women’s Health Initiative Observational Study (n=74 870), 50–79 years of age self-reported ST and PA at baseline, years 3 and 6. Incident CRC was the primary outcome; colon and rectal cancers were the secondary outcomes, which were centrally adjudicated. Over a 13-year follow-up period, 1145 incident cases of CRC were documented. A positive age-adjusted association was found between higher ST (≥10 vs. <5 h/day) and CRC (P for trend=0.04) and colon cancer (P for trend=0.05); however, these associations were attenuated and no longer significant in multivariable-adjusted models. Compared with inactive women (⩽1.7 MET-h/week), the multivariable risk of CRC in the high PA (>20 MET-h/week) group was 0.81 (95% confidence interval: 0.66–1.00; P for trend 0.04). Compared with inactive women with high ST (≥10 h/day), there was a trend toward reduced multivariable CRC risks with higher PA irrespective of ST level (interaction=0.64). We observed an inverse association between leisure time PA and the risk of CRC, particularly for rectal cancer. There was no association between ST and CRC in multivariable models.

Views of Cohort Study Participants about Returning Research Results in the Context of Precision Medicine

Background: The practice of biorepository-based genetics research raises questions related to what ethical obligations researchers have to their participants. It is important to explore and include the thoughts of current biorepository participants as we move forward with this type of research. Methods: Thirty participants (17 cancer patients, 7 cancer-free controls, and 6 relatives) were drawn from the Northwest Cancer Genetics Registry and participated in qualitative interviews lasting between 45 and 90 min. Topics explored in this study include which types of genetic test results participants of large biorepositories expect and would like to receive from research analyzing their samples, as well as thoughts on best practice for conducting this type of research. Results: Cancer cases, controls, and first-degree relatives have differing views on what results they would like to receive from biorepository-based research. Participants across all groups attempted to balance the costs and benefits of returning individual research results. Discussion: In the wake of precision medicine, it is important to describe the range of ways participants in large biorepositories both think and talk about the utilization of their specimens for genetics research.

Abstract 2599: Association of periodontal disease and breast health in women undergoing screening mammography

It is well established that chronic and persistent inflammation contributes to cancer development. Chronic inflammation is often associated with periodontal disease, or gum disease. Periodontal disease, which can be prevented or ameliorated by following proper oral hygiene, is known to be associated with various systemic disorders including coronary heart disease and some cancers, including head and neck cancer and pancreatic cancer. However, little is known about its potential association with breast cancer, with only one report in which periodontal disease was a positive predictor for breast cancer in a Swedish cohort. To examine if a potential link exists between periodontal disease and breast cancer in a separate cohort, mammography patients from the UC Irvine Athena Breast Health Network cohort were recruited to participate in a survey that included questions about their periodontal health. Diagnosis of invasive breast cancer, DCIS, and benign breast diseases was determined through data extraction from electronic medical records. There was no association between periodontal disease and DCIS or invasive breast cancer. However, there was a significant difference in the frequency of breast cysts among women with periodontal disease compared to women without periodontal disease (p Citation Format: Hannah Lui Park, Teofilia Acheampong, Kathleen Nguyen, Cindy Nguyen, Argyrios Ziogas, Richard Kelly, Andrea Alvarez, Kathryn M. Larsen, Deborah Goodman, Hoda Anton-Culver. Association of periodontal disease and breast health in women undergoing screening mammography. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2599.

Clinical Implementation of a Breast Cancer Risk Assessment Program in a Multiethnic Patient Population: Which Risk Model to Use?

Author(s): Park, Hannah Lui; Tran, Stephanie M; Lee, Jennifer; Goodman, Deborah; Ziogas, Argyrios; Kelly, Richard; Larsen, Kathryn M; Alvarez, Andrea; Tannous, Chris; Strope, Julie; Lynch, Wendy; Anton-Culver, Hoda | Abstract: The integration of risk assessment into clinical breast screening holds promise in decreasing breast cancer morbidity and mortality and increasing health care efficiency. Currently, clinical recommendations regarding risk counseling, screening, and chemoprevention are being made based on a woman’s personal risk. One of the criteria that can be used to categorize a woman as “increased risk” is her projected 5-year risk for invasive breast cancer as determined by one of various risk models which are heavily based on family history. We hypothesized that the frequency of screening mammography patients at our medical institution who would be considered at “increased risk” would be different according to different risk models and according to race/ethnicity, thus impacting the volume of patients who are targeted for risk-reducing intervention. Risk scores were calculated for 307 White, Hispanic, and Asian screening mammography patients according to the Gail, BCSC, and Tyrer-Cuzick models. Scores were compared within and between race/ethnicities, according to the different models, individually and in combination. As expected, White women had higher risk scores than Hispanic and Asian women according to all models tested (pl0.05), and a higher percent of White women were categorized as “increased risk” (pl0.0001). However, the correlations between models were moderate, resulting in inconsistencies of increased risk status for many women. Depending on the volume of patients undergoing risk assessment and the resources of staff and services providing the risk counseling and other downstream services, a prevention program may opt to use a combination of risk models suitable for their patient population instead of just one risk model.