Investigating the biological effects of socioeconomic adversity in cancer

Abstract

Numerous studies have demonstrated socioeconomic differences in cancer incidence and outcomes, including shorter cancer survival times in patients with lower educational attainment and income, which represent important indicators of lower socioeconomic status (SES). The hypothesis proposing that disparities in cancer outcomes and mortality linked to the social determinants of health (SDoH) can be accounted for by higher risk factor prevalences or the interrelation of various SDoH has been contradicted by current evidence and previous studies have introduced potential biological mechanisms of the SDoH which are summarised by the term ‘biology of socioeconomic adversity’. Socioeconomic inequalities in cancer risk and outcomes cannot be entirely attributed to differences in clinical, behavioural, and environmental risk factors in current clinical research. Hence, it is crucial to investigate various factors, including specific biomarkers and pathophysiological pathways affected by the SDoH.

For more than 30 years, numerous studies have demonstrated socioeconomic differences in cancer incidence and survival.^1-3 In the first place, it was found that shorter survival times in solid cancers and lymphoma are associated with lower income and education levels, two important indicators of lower SES, and it was noted that this effect could not be accounted for by the stage of disease at initial presentation and that this association persisted after statistically adjusting for all known prognostic factors.⁴ Today, socioeconomic inequalities in cancer survival rates still persist in clinical trials despite access to protocol-directed care,⁵ implying that optimal equitable healthcare cannot resolve inequalities in outcomes. For these reasons, a multiplex approach to this global health problem is necessary.

The hypothesis proposing that disparities in premature and cancer mortality linked to the SDoH can be accounted for by higher risk factor prevalences, like smoking, as well as by the interrelation of various SDoH, such as low income and living in adverse neighbourhood physical and social environments which aggregate within an individual, thereby amplifying health effects, holds significant appeal. However, it has been estimated that only about half of the association between area-level SES, which includes factors such as income, education, and occupation at the neighbourhood level, and cancer mortality risk can be explained by higher rates of individual-level risk factors including smoking, diet, physical activity, participation in cancer screening programs, and obesity.⁶ Even more, current evidence contradicts the idea that differences in cancer-associated mortality based on educational attainment, an often used indicator of individual-level SES and a key SDoH, can be attributed to differences in conventional cancer risk factors or the interrelation of multiple adverse SDoH at all.⁷ Still, participants of this large prospective population-based study having less than a high school degree as their highest educational qualification experienced a 50% higher risk of cancer-associated death when compared to those with a high school degree or higher.

It is reasonable to propose that non-intrinsic exogenous factors such as exposure to toxic substances, and endogenous factors including elevated levels of steroid hormones and inflammation, related to cancer risk are more prevalent in individuals with unfavourable SDoH. Previous studies have introduced potential biological mechanisms of the SDoH, which, collectively, may help explain persisting disparities in the risk of adverse outcomes by SES when controlling for established prognostic factors. Within the framework of the biology of socioeconomic adversity, stress-signaling pathways, gene expression, telomere attrition, and epigenetic regulation have been proposed to be associated with the SDoH.⁸ Chronic inflammation, immune and renal dysregulation have been shown to importantly mediate the effect of a lower education level on the risk of cardiovascular and all-cause mortality in patients with coronary artery disease, which were measured as elevated soluble urokinase Plasminogen Activator Receptor levels,⁹ a circulatory biomarker that is also highly predictive for cancer outcomes.¹⁰

It has to be acknowledged that socioeconomic inequalities in cancer risk cannot be entirely attributed to differences in clinical, as well as behavioural and environmental risk factors derived from epidemiological findings. Hence, it is crucial to investigate various factors including biomarkers and pathophysiological pathways affected by the SDoH. Collaborative efforts in population-based, clinical, and translational research are needed to alleviate the unequal burden of cancer within society. Biobank studies can identify different biomarkers associated with the SDoH and cumulative social disadvantage and explore their mediating effect on cancer outcomes. Also, investigating the pathophysiological mechanisms underlying changes in biomarker levels is needed to learn about the biology affecting outcomes in vulnerable populations. Ultimately, these findings may help inform clinical practice and health policy in the implementation of targeted preventive strategies to reduce cancer incidence and mortality.

David Füller: writing - original draft.

The author declares no conflict of interest.

No funding was received for this work.

Not applicable.