Introduction
Social determinants of health
Access to healthcare
Lifestyle factors
Psychological stress
Policy and interventions
References
Further reading
Introduction
Global scientific endeavors, such as the Human Cancer Genome Project and International Cancer Genome Consortium, have led to the genomic, epigenomic, and proteomic characterization of thousands of primary tumors. These efforts have demonstrated that most cancers typically begin with four or five mutations in specific genes, including oncogenes and tumor-suppressor genes1.
Importantly, advancements in molecular methods and techniques have allowed clinicians to classify cancers according to their genomic composition accurately, improving diagnoses, prognoses, and treatment efficacy.
Epigenetics, which is defined as heritable alterations in gene expression that do not cause direct changes to the DNA sequence, is another crucial aspect of carcinogenesis.
The three primary types of epigenetic changes observed in cancer include DNA and ribonucleic acid (RNA) methylation, histone modification, which can be further specified as acetylation, methylation, or phosphorylation, and the expression of non-coding RNA1. Any of these epigenetic alterations have the potential to inhibit tumor-suppressor mechanisms and/or directly activate oncogenesis.
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In addition to the genetic and epigenetic factors that contribute to cancer, recent studies have demonstrated that the sustained division of cancer cells is accompanied by stiffening of the extracellular matrix2. This subsequently induces changes in the tissue microenvironment, which further facilitate the uncontrolled cell division, as well as the invasion and migration of cancer cells to other tissues.
Non-biological factors have also been implicated in an increased risk of developing cancer, some of which include environmental pollutants, smoking, the consumption of processed foods, alcohol and drug use, obesity, physical inactivity, occupational exposure, and access to cancer screening3. Both individual- and area-level socioeconomic factors also significantly influence cancer incidence and mortality.
Social determinants of health
Social determinants of health (SDH) comprise non-biological factors, including societal systems and their components, as well as social resources and hazards controlled by these systems that affect a population's health.
Local and federal governments, institutions, as well as other organizations, regulations, and processes, encompass societal systems that have the power to control, allocate, withhold, and/or distribute resources and hazards for health. Some examples of health resources include food, shelter, safety, sanitation, civic participation, education, employment, law enforcement, and transportation.
Many studies have demonstrated that SDH may have a greater influence on health than genetic factors and access to healthcare services. This effect is further exacerbated when multiple SDHs often coexist within the same individual.
In fact, the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study found that individuals with two or more SDH or three or more SDH were at a 38% and 51% increased risk of stroke, respectively5.
Likewise, several studies have found that SDH, particularly the presence of multiple SDH, increases an individual’s risk of cancer mortality over time. In the United States, Black Americans have been repeatedly found to experience greater cancer mortality as compared to White Americans5.
Black adults in the general U.S. population have double the poverty and unemployment rates as compared to White adults, both of which are SDH that independently increase the risk of cancer mortality.
Systemic racism continues to have a pervasive impact on the health outcomes of communities of color, as it creates inequities in access to housing, education, wealth, and employment, all of which increase the risk of poor health outcomes in these affected populations.
Access to healthcare
Many of the differences that exist in both cancer incidence and mortality rates among population groups throughout the U.S., as well as much of the world, can be attributed to healthcare access, including cancer screening. With limited access to healthcare, affected individuals are more likely to be diagnosed with cancer at later stages, which has been estimated to have the largest contribution to survival disparities after socioeconomic factors and marital status.
For example, Black Americans are more likely to be diagnosed with advanced-stage colorectal, prostate, breast, and cervical cancers than White Americans of the same socioeconomic status3. Even after controlling for stage at diagnosis, Black Americans are also more likely to die from each of these types of cancers as compared to White Americans.
Private insurance has a significant protective effect against being diagnosed with advanced cancer. Nevertheless, the REGARDS study found that a greater number of SDH in the same individual increases their risk of cancer mortality, with this effect persisting in individuals 65 years of age and older who are eligible for Medicare, which is a federal health insurance option for the elderly in the United States5.
Lifestyle factors
Many chronic diseases will co-occur with cancers due to shared risk factors. Some of the most common comorbid diseases include obesity, diabetes, metabolic syndrome, cardiovascular, liver, and autoimmune diseases, as well as chronic infections.
Within the U.S., American Indians and African Americans are significantly more likely to be diagnosed with a comorbidity, the most common of which include obesity, diabetes, chronic kidney disease, and hypertension, each of which are also considered risk factors for cancer. In addition to increasing the risk of getting cancer, these chronic diseases can independently influence tumor biology and metastasis. The presence of comorbidity also limits potential cancer treatment options, particularly enrollment in cancer clinical trials.
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Many of these chronic diseases can be prevented and targeted through lifestyle changes. However, lower socioeconomic status often increases the risk of disadvantageous lifestyle habits such as smoking, diet, physical inactivity, and alcohol use6.
A high-calorie diet that is rich in fat and red meat intake, for example, increases the risk of colorectal, prostate, and breast cancer, whereas dietary patterns like the Mediterranean diet, which is associated with high consumption of fresh fruits and vegetables, whole grains, and limited meat, have been shown to be protective against cancer onset.
Physical activity also reduces the risk of several types of cancer, including lung cancer. In addition to their independent role in preventing cancer, both physical activity and diet are directly related to obesity, which increases the risk of cancer due to hyperinsulinemia.
Psychological stress
Many minority populations are exposed to stress throughout various stages of their life, ranging from intrauterine stress exposure to stressors during childhood that persist into early and late adulthood.
Prenatal stress exposure, for example, has been shown to shorten telomere length and alter DNA methylation processes, both of which have been implicated in premature aging processes and carcinogenesis. Likewise, growing up in a lower socioeconomic status increases pro-inflammatory signaling pathway activity, which ultimately increases the risk of cancer.
Two biological pathways implicated in the pathogenesis of chronic stress and its role in tumor biology involve catecholamines and glucocorticoids. Chronic stress leads to the increased release of catecholamines, which activate β-adrenergic signaling in both cancer cells and tumor-associated macrophages, thereby inducing a pro-metastatic environment around these cells6.
Perceived experiences of racism also cause chronic exposure to stress, which subsequently increases the likelihood that these affected individuals will also smoke and drink alcohol. In addition to the cancer risk associated with these behaviors,
Policy and interventions
Various policies have been implemented throughout the U.S. in an effort to reduce cancer disparities, as demonstrated by widespread smoking restrictions that have reduced the availability of tobacco, in addition to the implementation of public smoking cessation programs available for socially disadvantaged groups.
Despite these efforts, the significant role of both socioeconomic and racial/ethnic factors in the development of cancer indicates that these inequalities will likely persist for the foreseeable future. Therefore, there remains an urgent need to pass health policies that improve access to cancer screening programs in disadvantaged and underserved areas, in addition to improving social and physical environments that have a direct impact on cancer outcomes.
Since SDH has a synergistic role in an individual’s increased risk of cancer and death, public health strategies must account for these different factors to manage and target existing disparities that impact cancer mortality.
It is also crucial for federal institutions like the National Institutes of Health (NIH) to continue to fund cancer health disparity research to understand better the mechanisms by which certain lifestyle factors and comorbidities negatively impact cancer outcomes.
References
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Piña-Sanchez, P., Chavez-Gonzalez, A., Ruiz-Tachiquin, M., et al. (2021). Cancer Biology, Epidemiology, and Treatment in the 21st Century: Current Status and Future Challenges From a Biomedical Perspective. Cancer Control. doi:10.1177/10732748211038735.
- Motofei, I. G. (2022). Biology of cancer; from cellular and molecular mechanisms to developmental processes and adaptation. Seminars in Cancer Biology 86(3); 600-615. doi:10.1016/j.semcancer.2021.10.003.
- Singh, G. K., & Jemal, A. (2017). Socioeconomic and Racial/Ethnic Disparities in Cancer Mortality, Incidence, and Survival in the United States, 1950-2014: Over Six Decades of Changing Patterns and Widening Inequalities. Journal of Environmental and Public Health. doi:10.1155/2017/2819372.
- Hahn, R. A. (2021). What is a social determinant health? Back to Basics. Journal of Public Health Research 10(4); 2324. doi:10.4081/jphr.2021.2324.
- Pinheiro, L. C., Reshetnyak, E., Akinyemiju, T., et al. (2022). Social Determinants of Health and Cancer Mortality in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort study. Cancer 128(1); 122-130. doi:10.1002/cncr.33894.
- Minas, T. Z., Kiely, M., Ajao, A., & Ambs, S. (2021). An overview of cancer health disparities: new approaches and insights and why they matter. Carcinogenesis 42(1); 2-13. doi:10.1093/carcin/bgaa121.
Further Reading
Study shows cannabis as a genotoxic substance with cancer risks