Genomics: Insight

Understanding the role of societal inequities on the risk and outcome of Acute Myeloid Leukemia

We hypothesize that racial identity and socioeconomic status are associated with the risk for and mortality from acute myeloid leukemia through increased exposure to petrochemicals and lack of access to cancer healthcare. There is, however, contention about using race as a classifier.

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow that interferes with the production of normal white blood cells, therefore drastically lowering one’s ability to fight against other illnesses and carcinogens. Leukemia accounts for over 23,500 deaths annually, and in 2020, nearly half a million people in the U.S. were living with leukemia.¹ AML is the most common leukemia in adults and an extremely aggressive cancer. Cases of AML are still somewhat rare, accounting for 1% of total cancer cases. In the United States, the American Cancer Society reports around 20,800 new cases of AML per year and 11,220 deaths from AML per year.² Acute lymphocytic leukemia (ALL), another type of leukemia, is the most common childhood cancer and the number one disease-related reason for the death of children in the U.S.³

Leukemia accounts for over 23,500 deaths annually, and in 2020, nearly half a million people in the U.S. were living with leukemia

Genetic mutation of tumor-suppressor protein linked to AML

P53 is a tumor suppressor protein that is instrumental in cell division and triggers mechanisms to repair DNA damage or triggers a death signaling cascade if the DNA is too damaged. When p53 is mutated in the human body, the cell is able to replicate damaged DNA, sometimes leading to cancer. In a study done by Papaemmanuil et al. in 2016 with 1540 patients from the German-Austrian AML Study Group, researchers found that patients with AML caused by a TP53 mutation that results in an abnormal number of chromosomes had a poor chance of survival.⁴ The deleterious effects of the TP53 mutations were associated with the worst prognosis. Of all the mutations screened for, the gene whose mutation was most commonly associated with AML was P53. 18% of patients had two mutations, including a p53 mutation.

researchers found a significant increase in risk of mortality for women living within 2 and 6 km southeast of a petrochemical refinery.

Environmental factors

While genetic markers can predict risk for and mortality from AML, environmental factors such as access to healthcare and socioeconomic status also have a significant impact on the survival outcome of patients with AML.

Unequal access to cancer-related healthcare in the U.S. based on race
Using data from the California Cancer Registry, a study done in 2015 by Patel et al. determined whether minorities received different hospital treatment than non minorities and, as a result, how the outcomes of the patients differed.⁵ By analyzing 11,084 cases recorded from 1998-2008, researchers determined that Black race was associated with lower odds of chemotherapy. Black and Hispanic patients had decreased odds of receiving a transplant. Black patients also had an increased rate of mortality in comparison to white patients. After researchers adjusted the data for receipt of treatment, it resulted in decreased mortality for black patients.

Socioeconomic impacts on AML-associated mortality rates

In the United States, AML accounts for less than 20% of leukemia diagnoses but accounts for 50% of leukemia-related deaths. Socioeconomic status (SES) is one of the known factors in the risk of mortality from pediatric cancer. A review done by Knoble et al. in 2016 with data drawn from the US population and The Large Surveillance, Epidemiology, and Ed Results included 3652 cases of patients diagnosed with AML between 1973 and 2012.⁶ The study found two groups at a high risk: first, those who had the most extreme economic and educational disadvantages; second, those whose level of disadvantage was moderately high but also faced both immigration-related obstacles and housing instability.

Using data from the US National Cancer Institute Surveillance, Epidemiology and End Results Program (SEER), a study done in 2015 by Petridou et al. analyzed 28,804 cases of acute lymphoblastic leukemia (ALL), which is another type of leukemia.⁷ According to an individual-based level of SES, the study indicated that children from low SES suffered nearly twofold higher death rates from ALL. The survival gap between high and low SES seems wider in the United States; with relative risks for death for children with low SES increased compared to children in a high SES by a range of 20-82%.

The study indicated that children from low SES suffered nearly twofold higher death rates from ALL

Cancer risks for communities near petrochemical industrial complexes (PICs)

In an international review done in 2020 by Domingo et al., researchers concluded that “human exposure to carcinogenic pollutants emitted from petrochemical industries might increase cancer mortality and the incidence of some cancers, especially leukemia and other hematological malignancies, in some individuals residing in the neighborhood.”⁸ Based on 23 studies performed in Taiwan, Spain, the United Kingdom, Italy, and Nigeria; leukemia was the main type of cancer reported for people living near petrochemical factories. In a study done by Di Salvo et al. in Italy in 2015, researchers found a significant increase in risk of mortality for women living within 2 and 6 km southeast of a petrochemical refinery.⁹ The study included 171 cases and 338 controls. However, no association was found in 4 other investigations in various countries. More studies are needed to investigate the potential adverse health effects for communities living near petrochemical factories.

Socioeconomic impacts on petrochemical exposure

In a study done in association with the Houston Health Department, researchers measured the levels of formaldehyde, a carcinogenic air pollutant, emitted by PICs in Houston, Texas.¹⁰ The highest levels of formaldehyde were found in low-income areas populated by Black and Latino communities, such as Galena Park, Harrisburg, and Manchester. In Galena Park, which had a population of over 2000 in 2018, 40% of the individuals were below the poverty line, and 97% of the individuals were part of a minority. The levels of formaldehyde in this neighborhood, which lies close to the Houston Ship Channel, exceeded the EPA Chronic Health Screening Level and present a significant risk to the inhabitants of the neighborhood. This study in Houston shows that low-income communities, which are typically in the worst areas of a city due to historic redlining practices, near PICs will experience the most severe consequences from hazardous air pollutants emitted by PICs than other neighborhoods.¹¹

Future Outlook

The U.S. has a history of politicians creating zoning laws relegating people of certain races to certain areas that tend to be poorer and more dangerous. In cities with petrochemical factories, zoning laws can force people to live near petrochemical factories, exposing them to toxic chemicals. Further research is needed on the correlation between petrochemical exposure and increased risk for and mortality from AML. However, enough research has been done to show how detrimental petrochemical exposure can be and its link to socioeconomic status. Research has shown that exposure to petrochemicals can result in increased mortality rates and increased risk for cancers like AML. Added to increased exposure to petrochemicals, the people exposed tend to have a lower socioeconomic status and, therefore also, have less access to advanced cancer healthcare, creating a problem. We chose this topic because we wanted to explore the intersection of race and carcinogenesis further.

References

1. “Key Statistics for Acute Myeloid Leukemia” https://www.cancer.org/cancer/types/acute-myeloid-leukemia/about/key-statistics.html
2. “Cancer Stat Facts: Leukemia” https://seer.cancer.gov/statfacts/html/leuks.html
3. “The genomic landscape of pediatric acute lymphoblastic leukemia” https://pubmed.ncbi.nlm.nih.gov/36050548/
4. “Genomic Classification and Prognosis in Acute Myeloid Leukemia” https://www.nejm.org/doi/10.1056/NEJMoa1516192
5. “How do differences in treatment impact racial and ethnic disparities in acute myeloid leukemia?” http://www.ncbi.nlm.nih.gov/pubmed/25662426
6. “Socioeconomic status (SES) and childhood acute myeloid leukemia (AML) mortality risk: Analysis of SEER data” https://www.sciencedirect.com/science/article/abs/pii/S1877782116300935?via%3Dihub
7. “Socioeconomic disparities in survival from childhood leukemia in the United States and globally: a meta-analysis” https://pubmed.ncbi.nlm.nih.gov/25527416/
8. “Health risks for the population living near petrochemical industrial complexes. 1. Cancer risks: A review of the scientific literature” https://www.sciencedirect.com/science/article/abs/pii/S0013935120303881
9. “Spatial variation in mortality risk for hematological malignancies near a petrochemical refinery: A population-based case-control study” https://www.sciencedirect.com/science/article/abs/pii/S0013935115001681
10. “Formaldehyde Air Pollution in Houston” https://int.nyt.com/data/documenttools/2021-houston-formaldehyde-report-final-2021/51dcffdd0bcc17c0/full.pdf
11. “Living and Breathing on the Front Line of a Toxic Chemical Zone” https://www.nytimes.com/2023/05/05/us/politics/toxic-chemicals-restrictions-biden.html