Population screening shows risk of inherited cancer and familial hypercholesterolemia in Oregon.

The Healthy Oregon Project (HOP) is a statewide effort that aims to build a large research repository and influence the health of Oregonians through providing no-cost genetic screening to participants for a next-generation sequencing 32-gene panel comprising genes related to inherited cancers and familial hypercholesterolemia. This type of unbiased population screening can detect at-risk individuals who may otherwise be missed by conventional medical approaches. However, challenges exist for this type of high-throughput testing in an academic setting, including developing a low-cost high-efficiency test and scaling up the clinical laboratory for processing large numbers of samples. Modifications to our academic clinical laboratory including efficient test design, robotics, and a streamlined analysis approach increased our ability to test more than 1,000 samples per month for HOP using only one dedicated HOP laboratory technologist. Additionally, enrollment using a HIPAA-compliant smartphone app and sample collection using mouthwash increased efficiency and reduced cost. Here, we present our experience three years into HOP and discuss the lessons learned, including our successes, challenges, opportunities, and future directions, as well as the genetic screening results for the first 13,670 participants tested. Overall, we have identified 730 pathogenic/likely pathogenic variants in 710 participants in 24 of the 32 genes on the panel. The carrier rate for pathogenic/likely pathogenic variants in the inherited cancer genes on the panel for an unselected population was 5.0% and for familial hypercholesterolemia was 0.3%. Our laboratory experience described here may provide a useful model for population screening projects in other states.

REPRESENT recommendations: improving inclusion and trust in cancer early detection research.

Detecting cancer early is essential to improving cancer outcomes. Minoritized groups remain underrepresented in early detection cancer research, which means that findings and interventions are not generalisable across the population, thus exacerbating disparities in cancer outcomes. In light of these challenges, this paper sets out twelve recommendations to build relations of trust and include minoritized groups in ED cancer research. The Recommendations were formulated by a range of stakeholders at the 2022 REPRESENT consensus-building workshop and are based on empirical data, including a systematic literature review and two ethnographic case studies in the US and the UK. The recommendations focus on: Long-term relationships that build trust; Sharing available resources; Inclusive and accessible communication; Harnessing community expertise; Unique risks and benefits; Compensation and support; Representative samples; Demographic data; Post-research support; Sharing results; Research training; Diversifying research teams. For each recommendation, the paper outlines the rationale, specifications for how different stakeholders may implement it, and advice for best practices. Instead of isolated recruitment, public involvement and engagement activities, the recommendations here aim to advance mutually beneficial and trusting relationships between researchers and research participants embedded in ED cancer research institutions.

Equitable implementation of lung cancer screening: avoiding its potential to mirror existing inequities among people who use tobacco.

PURPOSE: Lung cancer is the leading cause of cancer death, but the advent of lung cancer screening using low-dose computed tomography offers a tremendous opportunity to improve lung cancer outcomes. Unfortunately, implementation of lung cancer screening has been hampered by substantial barriers and remains suboptimal. Specifically, the commentary emphasizes the intersectionality of smoking history and several important sociodemographic characteristics and identities that should inform lung cancer screening outreach and engagement efforts, including socioeconomic considerations (e.g., health insurance status), racial and ethnic identity, LGBTQ + identity, mental health history, military experience/veteran status, and geographic residence in addressing specific community risk factors and future interventions in efforts to make strides toward equitable lung cancer screening. METHODS: Members of the Equitable Implementation of Lung Cancer Screening Interest Group with the Cancer Prevention and Control Network (CPCRN) provide a critical commentary based on existing literature regarding smoking trends in the US and lung cancer screening uptake to propose opportunities to enhance implementation and support equitable distribution of the benefits of lung cancer screening. CONCLUSION: The present commentary utilizes information about historical trends in tobacco use to highlight opportunities for targeted outreach efforts to engage communities at high risk with information about the lung cancer screening opportunity. Future efforts toward equitable implementation of lung cancer screening should focus on multi-level implementation strategies that engage and work in concert with community partners to co-create approaches that leverage strengths and reduce barriers within specific communities to achieve the potential of lung cancer screening.

Rural research capacity: a co-created model for research success.

PURPOSE: The United States' National Institutes of Health (NIH) have long challenged academia to improve clinical trial enrollment, especially in underrepresented populations; inclusive of geography, age, disability status, racial and ethnic minorities. It has been shown that rural and urban residents enrolled in clinical trials have similar outcomes, yet, rural healthcare systems struggle to provide opportunities to rural residents to participate in clinical trials when infrastructure is limited or unsupportive of research programs and/or research staffing levels are insufficient. To fully address the barriers to clinical trial access in rural areas, it is not adequate to simply open more trials. Community receptivity of research as well as organizational and community capacity must be considered. This project was determined by the Oregon Health and Science University's Institutional Review Board to be generalizable research across the chosen counties and was approved to operate under a waiver of written consent. Participants received a cash incentive in appreciation for their time and verbally agreed to participate after reviewing a project information sheet. METHODS: The research team co-created a community-responsive approach to the receipt, review, and acceptance of clinical trials in a rural community setting. An adapted 5 step Implementation Mapping approach was used to develop a systematic strategy intended to increase the success, and therefore, the number of clinical trials offered in a rural community. RESULTS: The research team and participating rural community members pilot-tested the implementation of a co-designed research review strategy, inclusive of a Regional Cultural Landscape and three co-created project submission and feasibility review forms, with a cancer early detection clinical trial. The proposed clinical trial required engagement from primary care and oncology. Utilizing the research review strategy demonstrated strong researcher-community stakeholder communication and negotiation, which resulted in early identification and resolution of potential barriers, hiring a local clinical research coordinator, and timely trial opening. CONCLUSION: To the knowledge of the research team, the work described is the first to use a community-engaged approach for creating a clinical trial implementation strategy directly supportive of rural-sitting community stakeholders in receiving, reviewing, and approving cancer-related clinical trials in their community. Participating community members and leaders had the chance to negotiate research protocol changes or considerations directly with researchers interested in conducting a cancer clinical trial in their rural setting.

Disparities in pancreatic cancer care and research in Native Americans: Righting a history of wrongs.

Disparities in pancreatic cancer incidence and outcomes exist in Native American populations. These disparities are multifactorial, difficult to quantify, and are influenced by historical, socioeconomic, and health care structural factors. The objective of this article was to assess these factors and offer a call to action to overcome them. The authors reviewed published data on pancreatic cancer in Native American populations with a focus on disparities in incidence, outcomes, and research efforts. The historical context of the interactions between Native Americans and the United States health care system was also analyzed to form actionable items to build trust and collaboration. The incidence of pancreatic cancer in Native Americans is higher than that in the general US population and has the worst survival of any major racial or ethnic group. These outcomes are influenced by a patient population with often poor access to high-quality cancer care, historical trauma potentially leading to reduced care utilization, and a lack of research focused on etiologies and comorbid conditions that contribute to these disparities. A collaborative effort between nontribal and tribal leaders and cancer centers is key to addressing disparities in pancreatic cancer outcomes and research. More population-level studies are needed to better understand the incidence, etiologies, and comorbid conditions of pancreatic cancer in Native Americans. Finally, a concerted, focused effort should be undertaken between nontribal and tribal entities to increase the access of Native Americans to high-quality care for pancreatic cancer and other lethal malignancies.

Identify factors for insufficient (> 2 yr) mammogram screening among Oregonian women.

PURPOSE: Women with breast cancer diagnosed from mammogram screenings have a lower mortality risk than women diagnosed from symptoms. Currently, the U.S Preventive Services Task Force recommends biannual screening for women aged 50-74 years old. In this study, we aimed to identify factors associated with inadequate screening defined as "no mammogram screening within past 2 years" to guide cancer prevention and early detection efforts. METHODS: This study utilized area-based probabilistic sampling survey data, collected across Oregon in 2019. Dataset weights were calculated using a raking approach. Demographic and behavior information were collected with existing validated questionnaire items from national surveys. Weighted multivariable logistic regression analyses with missing-value imputations were conducted to identify factors associated with inadequate mammogram screening. RESULTS: The study included 254 women 50-74 years old without previous breast or ovarian cancer history. 19.29% of the sample reported no mammogram within two years, including 1.57% with no previous mammograms. Following unadjusted analyses, the significant factors included education, occupation status, health insurance and smoking and were therefore included into the adjusted model. In the multivariate adjusted model education remained significant while occupation status, health insurance and smoking were no longer significant. Compared to women with a college graduate degree, women with less than college graduate degree were at higher risk of inadequate screening [OR (95% CI) = 3.23 (1.54, 6.74)]. CONCLUSIONS: Lack of education was significantly associated with inadequate mammogram screening even after adjusting for occupation status, health insurance and smoking, which should prompt further outreach and education.

Diet-Driven Inflammation and Insulinemia and Risk of Interval Breast Cancer.

Interval breast cancers (IBCs) emerge after a non-suspicious mammogram and before the patient's next scheduled screen. Risk factors associated with IBC have not been identified. This study evaluated if the empirical dietary inflammatory pattern (EDIP) or empirical dietary index for hyperinsulinemia (EDIH) scores are associated with IBC compared to screen-detected breast cancer. Data were from women 50-79 years-old in the Women's Health Initiative cohort who completed food frequency questionnaires at baseline (1993-98) and were followed through March 31, 2019 for breast cancer detection. Women were identified as having either IBC diagnosed within 1-year after their last negative screening mammogram (N = 317) or screen-detected breast cancer (N = 1,928). Multivariable-adjusted logistic regression analyses were used to estimate odds ratios for risk of IBC compared to screen-detected cancer in dietary index tertiles. No associations were observed between EDIP or EDIH and IBC. Odds ratios comparing the highest to the lowest dietary index tertile were 1.08; 95%CI, 0.78-1.48 for EDIP and 0.92; 95%CI, 0.67-1.27 for EDIH. The null associations persisted when stratified by BMI categories. Findings suggest that diet-driven inflammation or insulinemia may not be substantially associated with IBC risk among postmenopausal women. Future studies are warranted to identify modifiable factors for IBC prevention.

How cancer programs identify and address the financial burdens of rural cancer patients.

PURPOSE: Financial toxicity is associated with negative patient outcomes, and rural populations are disproportionately affected by the high costs of cancer care compared to urban populations. Our objective was to (1) understand cancer programs' perceptions of rural-urban differences in cancer patients' experiences of financial hardship, (2) evaluate the resources available to cancer patients across the rural-urban continuum, and (3) determine how rural and urban health care teams assess and address financial distress in cancer patients. METHODS: Seven research teams within the Cancer Prevention and Research Control Network conducted semi-structured interviews with cancer program staff who have a role in connecting cancer patients with financial assistance services in both rural and urban counties. Interviews were audio-recorded and transcribed. We identified themes using descriptive content and thematic analysis. RESULTS: We interviewed 35 staffs across 29 cancer care programs in seven states, with roughly half of respondents from programs in rural counties. Participants identified differences in rural and urban patients' experiences of financial hardship related to distance required to travel for treatment, underinsurance, and low socioeconomic status. Insufficient staffing was an identified barrier to addressing rural and urban patients' financial concerns. CONCLUSIONS: Improved financial navigation services could mitigate the effects of financial toxicity experienced by cancer patients, particularly rural patients, throughout treatment and survivorship. Future research is needed to improve how cancer programs assess financial hardship in patients and to expand financial navigation services to better serve rural cancer patients.

Sulforaphane Bioavailability and Chemopreventive Activity in Men Presenting for Biopsy of the Prostate Gland: A Randomized Controlled Trial.

Previous studies suggest compounds such as sulforaphane (SFN) derived from cruciferous vegetables may prevent prostate cancer development and progression. This study evaluated the effect of broccoli sprout extract (BSE) supplementation on blood histone deacetylase (HDAC) activity, prostate RNA gene expression, and tissue biomarkers (histone H3 lysine 18 acetylation (H3K18ac), HDAC3, HDAC6, Ki67, and p21). A total of 98 men scheduled for prostate biopsy were allocated into either BSE (200 µmol daily) or a placebo in our double-blind, randomized controlled trial. We used nonparametric tests to evaluate the differences of blood HDAC activity and prostate tissue immunohistochemistry biomarkers between treatment groups. Further, we performed RNA-Seq analysis on the prostate biopsies and identified 40 differentially expressed genes correlated with BSE treatment, including downregulation of two genes previously implicated in prostate cancer development, AMACR and ARLNC1. Although urine and plasma SFN isothiocyanates and individual SFN metabolites were statistically higher in the treatment group, our results did not show a significant difference in HDAC activity or prostate tissue biomarkers. This study indicates BSE supplementation correlates with changes in gene expression but not with several other prostate cancer biomarkers. More research is required to fully understand the chemopreventive effects of BSE supplementation on prostate cancer.

Public perception of predictive cancer genetic testing and research in Oregon.

The potential for using widespread genetic testing to inform health care has become a viable option, particularly for heritable cancers. Yet, little is known about how to effectively communicate the benefits and risks of both personal genetic testing and participation in biorepositories that aid scientific advancements. Nationwide efforts are engaging communities in large genetic studies to better estimate the population-wide prevalence of heritable cancers but have been met with hesitance or declination to participate in some communities. To successfully engage an Oregon population in longitudinal research that includes predictive genetic testing for pathogenic or likely pathogenic variants associated with an increased risk for cancer, researchers conducted 35 focus groups (two of which were held in Spanish) in 24 of Oregon's 36 counties to better understand knowledge and attitudes related to genetic testing and willingness to participate in longitudinal genetic research. A total of 203 adults (mean = 45.6 years; range 18-88), representing a range of education levels and prior knowledge of genetic research, participated in the focus groups. The majority (85%) of participants reported personal or family diagnoses of cancer (e.g., self, family, friends). A majority (87%) also reported a strong interest in cancer genetic testing and receiving genetic information about themselves. Nearly all focus groups (94%, 33 of 35 sites) included participant discussion citing their families (e.g., children, close relatives, and extended family members) as key motivators for participation in genetic research. For example, participants reported interest in increasing personal knowledge about their own and their families' cancer risks in order to respond proactively, if a pathogenic variant was found. While most focus groups (94%, 33 of 35 sites) included participant discussion describing barriers to predictive genetic, testing such as concerns about outcomes, the desire to learn about health risks in oneself mitigated or outweighed those fears for many participants. Other commonly reported concerns were related to potential mistrust of insurance companies, researchers, or institutions, or lack of knowledge about genetics, genetic testing, or genetic research. Participants, particularly in rural areas, highlighted critical factors for research recruitment, such as trust, personal interaction, public education about genetic research, and clear communication about study goals and processes. Our statewide findings reflect that public interest in predictive cancer genetic testing and cancer genetic research can surpass lack of knowledge of the complex topics, particularly when benefits for self and family are emphasized and when study considerations are well articulated.