How the environment is silently shaping your risk for cancer

Cancer occurs when genetic changes disrupt cells’ normal functions. These genetic mutations can be inherited, happen spontaneously when cells make copies of themselves, or be caused by environmental carcinogens — chemicals capable of causing cancer.

While we can avoid some environmental carcinogens, like cigarette smoke and excessive sun exposure, it's much harder to avoid pollutants in the air and contaminants in our drinking water. As a result, it is crucial to understand which environmental factors are associated with cancer, where they are found, and how they contribute to cancer development. This understanding requires taking reliable measurements of environmental factors, gathering data from disproportionately affected populations, and devising experimental approaches to investigate their biological impact.

Researchers at the University of Chicago are helping lead this effort, leveraging large datasets, cutting-edge technologies and advanced methodologies to unravel the complex relationship between cancer and the environment.

Analyzing disparities through an environmental lens

Brisa Aschebrook-Kilfoy, PhD, MPH, MA, Associate Professor of Family Medicine at UChicago, is an expert in conducting environmental exposure assessments. She is actively leading efforts to build resources to study the impact of the urban exposome — the measure of everything an individual is exposed to in their lifetime — on human health, particularly cancer risk.

Earlier this year, her team published a paper detailing their first-of-its-kind analysis of air pollution data from the National Institute of Health All of Us research program, which has enrolled over 500,000 individuals representing diverse racial and ethnic backgrounds. They explored the association between the concentration of air pollutants in a person’s environment and their cancer risk.

The study found a significant association between higher levels of airborne pollutant particles in a person’s ZIP code and increased risk of several types of cancer (breast, ovarian, blood and endometrial). The researchers also found that risks differed by race and ethnicity. For instance, they observed an increased risk of blood cancers among non-Hispanic Black and Asian people, and increased risks of bone, breast and endometrial cancers among Hispanic people.

“Our hope is this work supports further consideration of the role of the environment on cancer disparities both in Chicago and nationally,” Aschebrook-Kilfoy said.

Anand A. Patel, MD, a medical oncologist and researcher at UChicago Medicine, also studies the impact of environmental factors on cancer. Her research centers on studying novel therapies and improving the standard of care for patients with blood cancers, with a special interest in the impact of air pollutants in the Chicago area.

In a prior study, Patel and colleagues demonstrated poorer leukemia-related outcomes among non-Hispanic Black and Hispanic patients compared to non-Hispanic white patients with acute myeloid leukemia (AML). The disparity was largely attributed to structural racism; however, individual components that contribute are not fully known. In a new study, Patel and colleagues investigated the impact of air pollutant exposure on disease characteristics and survival outcomes in AML.

They found that in a Chicagoland cohort of patients with AML, non-Hispanic Black and Hispanic patients were exposed to higher levels of pollutants associated with leukemia when compared to non-Hispanic white patients. They also found that increased exposure to polycyclic aromatic hydrocarbons and polycyclic organic matter in the air was associated with higher-risk disease features.

The cellular and genetic impact of environmental carcinogens

To further understand how environmental factors might contribute to disease mechanisms, researchers are exploring those factors’ cellular and genetic impact. Yu-Ying He, PhD, Professor of Medicine, and Muhammed Kibriya, MD, PhD, Research Associate Professor at the Institute for Population and Precision Health (IPPH), are applying a range of molecular genomic approaches to study the impact of environmental carcinogens.

He's group is studying the interaction between environmental carcinogens and the epitranscriptome — chemical modifications that regulate gene expression without altering the DNA sequence. The team has developed sophisticated cell and mouse model systems that allow them to precisely dissect the effects of various carcinogens, including arsenic exposure.

“Genetics and epigenetics are known to play critical roles in gene-environment interactions in health and diseases. Now epitranscriptomics is introducing a new layer of mechanisms in environment-associated diseases, including cancer,” He said. 

"In the future, identifying the specific profiles of epitranscriptome-environment interactions can not only help us understand how environmental exposure increases cancer risk, but also may identify new targets and pathways for evidence-based cancer prevention, interception and therapy.”

Similarly, Kibriya has investigated the effects of arsenic exposure in Bangladesh for several years. In the past, some of his research has aimed to provide insights into the genetic and environmental factors that influence an individual’s susceptibility to arsenic toxicity.

In a recent paper, Kibriya and his colleagues characterized the patterns of mutations in non-melanoma skin cancer (NMSC) in individuals exposed to arsenic through drinking water.

They identified NMSC-associated mutations and showed how they affect cancer-related gene pathways (changes in RNA levels).

“These gene-environment interactions may have implications on precision medicine for patients who need medical therapy in addition to surgical removal of the tumor,” Kibriya said.

Population-level data for studying environmental health

As researchers delve deeper into understanding how environmental factors contribute to cancer, the need for population-level data becomes increasingly important.

Habibul Ahsan, MD, MMedSc, Louis Block Distinguished Service Professor of Public Health Sciences and Dean of IPPH, is a leader in building cohorts for large-scale studies both nationally and globally. Ahsan holds leadership positions in the Chicago Center for Health and Environment (CACHET), Chicago Multiethnic Prevention and Surveillance Study (COMPASS), Health Effects of Arsenic Longitudinal Study (HEALS), and the NIEHS-funded Environmental Health Core Center in Chicago, to name a few. To him, the size of these endeavors is exciting rather than daunting.

“Doing research in a global health context has unique advantages such as large population sizes, high compliance from researchers and participants, and high health impact," Ahsan said. "When studying the role of environmental factors in cancer risk and development, these advantages can be particularly beneficial and contribute to meaningful public health outcomes.” 

A common theme across these major research programs is the focus on combining environmental, nutritional and lifestyle factors with molecular genomics to explore the causes, development, prognosis and prevention of cancer and other diseases of public health concern.

Findings from Ahsan’s environmental health studies have informed policy decisions and led to the development of targeted public health programs. For example, his group reported in 2006 that arsenic in drinking water is associated with a higher risk of developing pre-cancerous skin lesions, contributing to the Environmental Protection Agency lowering the legal limit of arsenic in United States drinking water.

An urgent priority

In today’s rapidly changing world, where shifts in air, water and sand quality, climate patterns, and chemical exposures from consumer products and foods are abundant, the work by researchers at UChicago has significant implications for public health and can influence policies that promote a more equitable future for all populations.

In November 2024, the UChicago Medicine Comprehensive Cancer Center’s annual Cancer Disparities and Health Equity Symposium will delve further into these topics, featuring talks from leading experts like He and Aschebrook-Kilfoy.