Hawai‘i Minority Health and Cancer Disparities SPORE

University of Hawai‘i

Principal Investigators

Overview

At the root of health disparities is the diversity that exists in the biological, behavioral, sociocultural, and environmental characteristics of individuals and populations. Hawai‘i offers exceptional opportunities for minority health research due to its uniquely diverse population. Hawai'i's population has varying cancer burdens as well as high-quality health care and cancer registration. The University of Hawai‘i Cancer Center (UHCC) has a successful track record of leveraging Hawai‘i’s multiethnic population to study racial/ethnic differences in cancer risk and outcomes. The goal of this planning grant is to establish a Specialized Programs of Research Excellence (SPORE) program to conduct translational research focusing on Asian Americans, Native Hawaiians, and Pacific Islanders (AANHPI), the fastest growing U.S. minority. We aim to address cancers of particular relevance to these populations.

Project 1 addresses the excess lung cancer burden experienced by Native Hawaiians by developing a risk-based and culturally informed lung cancer screening strategy. It investigates the mutation, methylation, and transcriptomic profiles of lung tumors in Native Hawaiians compared to White people.

Project 2 addresses the very high breast cancer burden of Native Hawaiians and the sharply rising rates of breast cancer in Asian Americans. It accomplishes this by testing the adequacy of current radiomic risk prediction algorithms for predicting breast cancer in these populations and by investigating related molecular and histopathologic features of the breast tumor microenvironment, which may be related to visceral adiposity and have prognostic significance.

The SPORE is supported by

1. an Administrative Core with strategic planning, scientific and community advisory, and evaluation components;
2. an Outreach and Recruitment Core facilitating studies among minorities;
3. a centralized biorepository of paired fresh-frozen tumor and blood samples, as well as archival tumor blocks (Pathology & Biospecimen Core);
4. a Biostatistics & Bioinformatics Core;
5. a Developmental Research Program to fund innovative pilot studies and a Career Enhancement Program to support promising investigators new to translational research; and
6. new collaborations, with other institutions for the further translation of our findings.

The successful completion of this program will significantly advance our ability to reduce the high cancer burden in the AANHPI population and to conduct innovative translational minority health research that will benefit Hawaii, the Pacific region and the rest of the U.S.

Project 1: Mitigating Lung Cancer Disparities in Native Hawaiians — A Population-Based Approach to Evaluate Prevention Barriers and Lung Tumor Biology

Project Co-Leaders

• Jeffrey Berenberg, M.D., M.A.C.P. (Clinical Co-leader)
• S. Lani Park, Ph.D. (Applied Co-leader)
• Lenora Loo, Ph.D. (Basic Co-leader)

We have shown that the Multiethnic Cohort that Native Hawaiians have a markedly higher risk of lung cancer and poorer survival from the disease compared to (non-Hispanic) White people. This is apparent even after accounting for smoking history and other factors. This excess risk was observed for all cell types, however the poorer survival was observed for early stage cancer only. While the high risk in African Americans and low risk in Japanese Americans can be explained by higher and lower smoking intensity (carcinogens dose per cigarette), due to smoking behavior and lower nicotine metabolism, respectively, reasons for the excess risk in Native Hawaiians remain unknown. Lung cancer screening was performed using low-dose computed tomography (LDCT) among smokers aged 50-80 years who have a 20+ pack-year history, or have quit within the past 15 years. This screening has been shown to decrease mortality. However, the state of Hawaii ranks last in the proportion of lung cancers diagnosed at an early stage (19% vs. 24% nationally).  Less than 3% of high-risk smokers undergo LDCT screening, compared to the national average of 6%. Studies have suggested that the use of risk-based prediction models may be more effective than the U.S. Preventive Services Task Force (USPSTF) criteria at identifying high-risk smokers for lung cancer screening. However, both the USPSTF guidelines and these risk models were derived from mostly European-descent populations. There may be distinct biological processes that contribute to the excess risk and poor outcome for Native Hawaiians. For example, we observed differences in epigenetic patterns in blood DNA associated with smoking dose in Native Hawaiians compared to other groups, with the differential methylation occurring in cancer-related genes. Project 1 is conducting a multilevel study to:

Specific Aims

• Aim 1: Identify the individual and provider-based barriers for lung cancer screening to develop an intervention strategy to be disseminated with the Hawaii Department of Health.
• Aim 2: Better identify those at greatest risk of developing lung cancer by computing a Native Hawaiian-specific risk prediction model.
• Aim 3: Characterize the tumor pathobiology associated with the poor survival of Native Hawaiian lung cancer patients. Study findings will provide critical information along the continuum of lung cancer healthcare for a high-risk minority population.

Project 2: Inter-Relationships and Prognostic Significance of Breast Cancer Radiomic Risk Features, Tissue Microenvironment and Adiposity 

Project Co-Leaders

• John Shepherd, Ph.D. (Applied Co-leader)
• Jami Fukui, M.D.( Clinical Co-leader)
• Lenora Loo, PhD (Basic Co-leader)
• Brenda Hernandez, Ph.D. (Applied Co-leader)

The risk of breast cancer among U.S. women differs dramatically across racial and ethnic populations. Nonetheless, Asian Americans, Native Hawaiians and Pacific Islanders (AANHPI) have been historically underrepresented in breast cancer research. Consequently, there are major gaps in understanding disparities in these populations, including high incidence and mortality among Native Hawaiians and a steadily rising incidence with comparatively favorable outcomes among Japanese Americans. Obesity and breast density, established breast cancer risk factors, vary widely across AANHPI women and have direct implications for mammographic screening and primary prevention. Our research to date provides strong evidence that body fat distribution, specifically, visceral adipose tissue (VAT), is an important predictor of breast cancer risk. The influence of adiposity on breast density and other aspects of breast architecture that can be discerned through mammographic screening (e.g., radiomic features) is not well understood. Our long-term goal is to elucidate the breast cancer disparities seen in understudied minority AANHPI subgroups that can be translated to improved prevention, early detection, and therapeutic strategies. Our central hypothesis is that established radiomic risk features have unique associations with breast cancer incidence in AANHPI subgroups and that they are correlated with tissue biomarkers of risk and prognosis and with obesity, especially VAT. Study resources include the statewide Hawai‘i Pacific Islands Mammography Registry, the Hawai‘i Tumor Registry and its Residual Tissue Repository, and the Multiethnic Cohort Study (MEC). Our aims are to:

Specific Aims

• Aim 1: Characterize the relationships of established breast imaging radiomic risk features with tissue protein biomarker expression profiles reflecting the tissue microenvironment and breast cancer prognosis and with disease-specific survival.
• Aim 2: Characterize the joint relationships of breast radiomic risk features and measures of adiposity, including VAT, with post-menopausal breast cancer risk among MEC participants.
• Aim 3: Calibrate commonly used risk prediction models for breast cancer by including established breast radiomic (AI and machine learning) risk features from 2D and 3D mammography in AAPHI and White women overall and by estrogen/ progesterone receptor and HER-2 status. Project 2 will improve risk and prognosis model accuracy and better identify high risk women for further assessment or tailored therapy.

Administrative Core

Core Co-Directors

• Loic Le Marchand, M.D., Ph.D.
• Jeffrey Berenberg, M.D., M.A.C.P.

The purpose of the Administrative Core is to provide the leadership and administrative management for the proposed multidisciplinary P20 SPORE aimed at capitalizing on the infrastructure at the University of Hawaii Cancer Center (UHCC) and the racial/ethnic diversity of its catchment area to conduct translational research addressing the racial/ethnic differences in cancer risks and outcomes that exist in Hawaii and the Pacific. The Administrative Core builds upon a number of UHCC resources, both administrative and scientific, to foster the implementation and coordination of the research in this SPORE. This Core will also closely coordinate the P20 resource-building and career-development activities with those implemented by UHCC, so greater efficiency is achieved at the institutional level. Thus, this Core serves major administrative and integrative functions for the SPORE.

Biostatistics and Bioinformatics Core

Core Co-Directors

• Lynne Wilkens, Dr.P.H.
• Youping Deng, Ph.D.

The goal of the Biostatistics and Bioinformatics Core (BBC) is to provide support to the SPORE projects, other cores, as well as the researchers funded through the Developmental Research Program or Career Enhancement Program in all aspects of study design and data management, processing, integration, and analysis.

Specific Aims

• Aim 1: To provide support for data management and integration for the projects, while ensuring data quality and security processes are incorporated.
• Aim 2: To develop and execute study design and analysis plans for each of the research projects, in conjunction with Project Leaders; and
• Aim 3: To facilitate data sharing among SPORE researchers and with the research community.

Pathology and Biobanking Core

Core Co-Directors

• Brenda Hernandez, Ph.D.
• Owen Chan, M.D., Ph.D.

The lack of research specimens from racial and ethnic minority populations in the U.S. remains a barrier to understanding racial/ethnic differences in cancer development, progression, and outcomes. In particular, the paucity of clinical biospecimens from understudied populations, including Native Hawaiians, other Pacific Islanders, and Asian Americans (AANHPI), has limited our ability to address critical disparities in cancer risk and outcomes affecting these U.S. communities. The Pathology and Biospecimen Core integrates and augments existing and new biospecimen resources with respect to their acquisition, processing, tracking, storage, and distribution and will support Project 1 (lung cancer), Project 2 (breast cancer), Career Enhancement Program (CEP) and Developmental Research Program (DRP) projects, as well as other UHCC investigations. Our goal is to develop a robust infrastructure to address differences in cancer risk and outcomes in AANHPI ethnic minority populations. Aim 1 focuses on developing a repository of paired fresh frozen tumor tissue and blood specimens from multiethnic cancer cases diagnosed in the state of Hawaii with cancers of the lung, liver, breast, colorectum, endometrium, pancreas, and stomach. Potential cases will be identified via rapid reporting from medical facilities statewide through the NCI SEER Hawaii Tumor Registry. Aim 2 is to provide biospecimens from new and existing resources in support of Projects 1 and 2, CEP and DRP projects, and future cancer research projects.

Specific Aims

• Aim 1: To develop a multiethnic biospecimen repository of paired fresh frozen tumor tissue and blood specimens from Hawai‘i residents diagnosed with cancers of the liver, lung, breast, colorectum, endometrium, pancreas, and stomach. Individuals — including Native Hawaiians, Micronesians, Samoans, Filipinos, Japanese, other Asians, and non-Hispanic Whites — will be identified at medical facilities of the statewide Hawai‘i Cancer Consortium through rapid case ascertainment by the NCI SEER Hawai‘i Tumor Registry in order to ensure population representation.
• Aim 2: To provide biospecimens from new and existing resources in support of Project 1, Project 2, Project 3, Career Enhancement Program (CEP) and Developmental Research Program (DRP) projects, and future cancer minority health and cancer disparities research in Hawai‘i.

Developmental Research Program

Program Co-Directors

Gertraud Maskarinec, M.D., Ph.D.

The Developmental Research Program (DRP) will draw upon areas of unique opportunity at UHCC to foster minority health research that will improve our biological understanding of ethnic/racial differences in cancer risk and outcomes in our catchment area and translate our findings into therapeutic, behavioral, and diagnostic clinical trials and interventions that address these challenges. The DRP is a central element of the P20 for developing new translational research projects in minority health that will nurture new lines of investigation, research innovation, and collaboration. The funded pilot projects will provide important preliminary data for future large research project applications and support their feasibility and impact. Therefore, the DRP is an engine for innovation in translational minority health research at UHCC. The goal of the DRP is to identify and fund new research projects and collaborations that address minority health issues in UHCC’s catchment area. In support of this goal, the DRP coordinates pilot funding requests, reviews, and award activities and identifies areas of unique opportunity and potential collaborations. These projects will form the basis for the continued success of this minority health SPORE and expand its impact by fostering the development of new research topics.

Specific Aims

• Aim 1: Coordinate Pilot Funding activities.
• Aim 2: Identify areas of unique opportunity for pilot projects and collaborations, and facilitate these efforts.

Career Enhancement Program

Program Co-Directors

Gertraud Maskarinec, M.D., Ph.D.

The goal of the Career Enhancement Program (CEP) is to identify and mentor investigators who show promise for independent research careers in translational research in minority health and in correcting ethnic/racial disparities in cancer. The CEP provides funding and mentoring to junior faculty who are developing an independent research program. It also provides support to established investigators to greatly enhance or refocus their careers on minority health research. In service of this goal, the CEP:

1. coordinates identification of promising new research in disparities research from junior faculty and established investigators who are looking to refocus their research in this area;
2. provides training, career development and mentoring to awardees in minority health research;
3. monitors the progress of CEP awardees as they develop independent careers and/or new research programs in minority health, and assesses the effectiveness of the CEP approach.

Specific Aims

• Aim 1: Coordinate identification and implementation of promising new research in minority health and disparities research from junior faculty and established investigators looking to refocus their research in this area.
• Aim 2: Provide training, career development and mentoring of awardees in minority health research.
• Aim 3: Monitor the progress of CEP awardees to develop independent careers and/or new research programs in minority health and assess effectiveness of the CEP itself.