# Understanding Cancer Health Disparities

## TL;DR

This paper explores how DNA damage and social factors together contribute to cancer health disparities, especially in marginalized groups like Native Hawaiians and Pacific Islanders.

## Contribution

The paper introduces a translational framework linking social determinants to DNA damage mechanisms to explain cancer disparities.

## Key findings

- DNA damage and genomic instability act as a bridge between social inequities and cancer susceptibility.
- Native Hawaiians and Pacific Islanders face elevated gastrointestinal cancer rates due to historical, environmental, and socioeconomic factors.
- Interdisciplinary strategies are needed to address cancer disparities by targeting root causes of genomic instability.

## Abstract

Cancer health disparities—differences in cancer measures including new cancer cases, all existing cases, mortality, survivorship, screening rates, stage at diagnosis, etc.—are influenced by complex interactions between biological, environmental, and social factors. DNA damage studies provide critical insights into these disparities by unraveling how genetic instability, repair deficiencies, and environmental exposures disproportionately affect marginalized groups. Below, we discuss the factors eventually driving genomic instability leading to cancer susceptibility, and how these factors are integrated in the real world and lead to cancer health disparities, such as among Native Hawaiians/Pacific islanders (NH/PI).

Cancer health disparities represent profound inequalities in incidence, outcomes, and survivorship across populations. While traditionally examined through distinct lenses of either molecular biology or social epidemiology, these disparities arise from the complex interplay of genetic susceptibility, epigenetic dysregulation, and social determinants of health (SDoH). This review proposes that DNA damage and genomic instability serve as a critical mechanistic bridge, integrating exposures from the societal level to cellular dysfunction. We synthesize evidence demonstrating how SDoH—such as systemic inequities, environmental exposures, and chronic stress—converge with genetic and epigenetic factors to disproportionately increase DNA damage burden, impair repair mechanisms, and accelerate tumorigenesis in marginalized communities. Using the elevated gastrointestinal cancer rates among Native Hawaiians and Pacific Islanders (NH/PI) as a case study, we illustrate how historical, environmental, and socioeconomic factors interact with biological pathways to drive disparities. The review highlights key advances in DNA damage research—from somatic mutation theory to the modern understanding of chronic genomic stress—and explores how innovations in single-cell genomics, biomarker discovery, and computational modeling can unravel disparity etiologies. We argue that a translational framework linking social exposure data to molecular biomarkers of DNA damage is essential for moving beyond descriptive disparities to mechanistic understanding. Ultimately, addressing cancer equity requires interdisciplinary strategies that bridge molecular oncology, public health, and community-engaged research, targeting the root causes where social inequities become biologically embedded as genomic instability.