Across all kinds of cancer, Black Americans have higher rates of mortality and, often, more aggressive forms of the disease. A growing body of research suggests the reasons may not have to do with African ancestry as much as social and environmental factors like racism, housing discrimination, and — according to a new study — exposure to pollution.
The study, published in Nature Communications, found that in several types of cancer, Black patients had more cancers with extra copies of genes. But the team found that these genetic duplications, which can make cancers more aggressive, didn’t seem to be linked to anything ancestral. Rather, the team reported genetic duplications were more likely in cells exposed to pollutants.
“What this paper hints at, is that we’re seeing something which looks like a genetic difference, but the source of that might actually not be genetic — it’s more environmental,” said Kanika Arora, a computational biologist at Memorial Sloan Kettering who was not involved with the new study.
The study analyzed data from three existing cohorts of just over 23,000 cancer patients, including around 1,800 Black patients. Previous research on genetic causes of disparities often focused on point mutations, or changes to individual base pairs. But researchers working on the new paper zoomed out and investigated cases where the whole genome of a cell had been duplicated.
“These are not changing the sequence of the gene, they’re changing its dosage in the cell, and this has been recognized to influence cancer in a variety of ways,” said Jason Sheltzer, a geneticist at Yale School of Medicine who co-authored the study.
Whole genome duplications can make tumors more adaptable and help them spread more easily, leading to worse prognosis for patients. But whether or not they influenced racial disparities in cancer mortality rates had not previously been studied.
The study found that whole genome duplications were anywhere from 11% to 35% more common in Black patients than in white patients. Sheltzer’s team initially began looking for potential genetic drivers of these differences, but “we didn’t find anything unique in African American patients,” he said. “We found basically all the usual suspects when we looked at tumors in African Americans. So we couldn’t say that there was some unique genetic lesion that was driving these whole genome duplication events in Black cancer patients.”
Since epidemiological studies have shown that Black Americans are exposed to more carcinogenic pollutants than other groups, the team decided to explore environmental factors. They exposed mouse cells to common pollutants known to be carcinogens, such as byproducts of combustion from cars. Several of the pollutants they tested increased the rate at which cells experienced whole genome duplications.
This suggests higher exposures to pollutants could be fueling disparate cancer outcomes, according to the paper’s authors. Outside researchers said this study is the first step in understanding how environmental inequities can fuel differences in cancer outcomes.
“I don’t think we know really well what exposures are contributing to whole genome doubling,” said Rameen Beroukhim, a neuro-oncologist at the Dana-Farber Cancer Institute and Harvard Medical School.
But he added that evidence increasingly suggests that “exposures that [different racial groups] face could absolutely contribute to both different rates of cancer and among the cancers that do occur, different molecular features of those cancers.”
Outside experts noted that one shortcoming of the paper points to a larger issue in the field. Black people made up 7% of the patients represented in the datasets, but 13% of the total U.S. population. The more limited data makes it difficult to answer specific questions about cancer subtypes and the effects of certain pollutants, or to be certain that any associations the researchers saw were real signals of a connection between pollutants and more aggressive cancers.
“The genomic data that we have from people of African ancestry is small, and so we’re not as well powered as we could be to detect these sorts of molecular associations,” Beroukhim said.
But the study highlights the need to reduce people’s exposure to pollutants and the importance of prioritizing genetic screening to understand a person’s individual cancer risk, according to Melissa Davis, the head of the Institute of Genomic Medicine at Morehouse School of Medicine. Davis also notes if pollutants are driving disparate cancer rates, cancer treatment and prevention methods need to change accordingly.
“We treat patients, we treat their tumor, and then we send them right back into the environment, which we’re saying is causing their cancer, but then we don’t give them any additional information,” she said. “If it truly is that exposure that’s driving the cancer, we need to then work with our communities to be more informed, and then drive policies around that.”
