Ethnic Disparities in Childhood Cancer Survival: Biology, Socioeconomics, or Both?
Ethnic disparities in childhood cancer outcomes are poorly understood. Competing narratives have emerged, emphasizing socioeconomic differences such as access to care or differences in biology between children of different ethnic backgrounds.
However, the underlying factors are likely complex and multifaceted. It appears likely that both socioeconomic and biological differences contribute to ethnic disparities in cancer survival. Recent research suggests that genetic variants associated with childhood leukemia risk, chemotherapy toxicity, and relapse risk might be over-represented among children in an ethnic minority.
Although ethnic disparities in cancer treatment outcomes have been less thoroughly studied among children than adults, children of Hispanic, African-American, and American Indian ethnicity do appear to experience poorer cancer outcomes than children of other ethnicities in the United States.1-4 These ethnic disparities are evident in mortality rates, as well as overall survival (OS) and event-free survival rates among children with cancer.1,2
Ethnic disparities in childhood cancer survival are part of a larger and long-standing pattern of disparate pediatric mortality rates; these disparities have persisted despite significant overall declines in mortality rates associated with pediatric cancer and other causes during the late 20th century.1,5,6 Cancer survival disparities are not limited to children; in one recent national database study of patients of all ages with acute leukemias, for example, African-American and Hispanic-American patients were found to face significantly poorer survival rates than do patients of non-Hispanic white ethnicity.7
Are Genetics to Blame?
Competing biologic and socioeconomic narratives about underlying factors in cancer outcome disparities have emerged in recent research. Socioeconomic factors such as clinical cancer care quality and access, appear to be relevant in understanding outcome disparities—but increasingly, so do genetic polymorphisms.1,8,9
It has been suggested that ethnic differences in therapy adherence rates deserve systematic study. For instance, the frequency of glutathione S-transferase (GST) gene variants associated with acute toxicity during maintenance or continuation therapy vary between ethnic populations in a way that might influence relapse risk in childhood ALL.1
In addition, he ARID5B single nucleotide polymorphism (SNP) is associated with susceptibility to childhood acute lymphoblastic leukemia (ALL).9 According to a 2012 analysis published in the Journal of Clinical Oncology, which included data from 1,308 children in the United States with ALL and 1,587 control-group children, ARID5B SNP genotypes are also associated with poorer ALL treatment outcomes—and they occur more frequently among Hispanics and American Indians compared with Caucasian patients.9
“To the best of our knowledge, this is the first report describing the relation between ARID5B and ALL treatment response in the context of a frontline ALL clinical trial,” the authors reported. “Interestingly, we previously observed that ARID5B is associated with leukemic cell accumulation of methotrexate metabolites (ie, polyglutamated methotrexate), offering a plausible mechanism by which ARID5B is linked to ALL relapse.”9
Since socioeconomic factors are strongly associated with ethnicity, causal analysis can be a daunting task. Outcome disparities “are likely not only due to genetic differences in disease biology; socioeconomic status is strongly correlated with race/ethnicity, and is a robust predictor of access to and quality of health care, which, in turn, may be associated with outcome,” notes Smita Bhatia, MD, MPH, of the City of Hope Cancer Center in Duarte, CA.1 “Thus evaluation of whether genetic differences underlie racial disparities in outcome should take into account socioeconomic status and access to care, and vice-versa.”
Addressing the Disparities: Where Do We Go?
Ultimately, to statistically disentangle the influences of health care access and quality from biological differences, “there must be standardization of care,” notes Lori Jordan, MD, PhD and Michael R. DeBaun, MD, MPH, of the Vanderbilt University Medical Center in Nashville, TN.6 “[N]amely, individuals with the same disease must be evaluated and treated approximately the same, with equal access to treatment and supportive services. Pediatric cancer provides an example where, regardless of race, equal access to quality health care and identical protocol-based treatments occur, and yet the question still remains whether there is a significant difference in black-white survival.”6
Some systems of care that offer equal access do not report ethnic disparities in survival seen in analyses of national childhood cancer data, for example.2,10 Socioeconomic and biological factors can no longer be isolated explanations for cancer-outcome disparities. Rather, accumulating evidence indicates that interrelated socioeconomic, behavioral, and genetic factors all play a role in explaining ethnic disparities in childhood cancer survival.
1. Bhatia S. Disparities in cancer outcomes: Lessons learned from children with cancer. Pediatric Blood Cancer. 2011;56(6):994-1002.
2. Pui CH, Pei D, Pappo AS, et al. Treatment outcomes in black and white children with cancer: results from the SEER database and St Jude Children's Research Hospital, 1992 through 2007. J Clin Oncol. 2012;30(16):2005-2012.
3. Goggins WB, Lo FF. Racial and ethnic disparities in survival of US children with acute lymphoblastic leukemia: evidence from the SEER database 1988-2008. Cancer Causes Control. 2012; 23:737-743.
4. Amirian ES. The role of Hispanic ethnicity in pediatric Wilms' tumor survival. Pediatr Hematol Oncol. 2013;30(4):317-327.
5. Singh GK. Child mortality in the United States, 1935-2007: Large racial and socioeconomic disparities have persisted over time. US Health Resources and Services Administration (HRSA). http://www.hrsa.gov/healthit/images/mchb_child_mortality_pub.pdf. Accessed Sept. 25, 2013.
6. Jordan LC, DeBaun MR. Pediatric stroke, health disparities, and biological differences in disease pathophysiology. JAMA Pediatrics. 2013;167(8):695-697.
7. Patel MI, Ma Y, Mitchel BS, Rhoads KF. Understanding disparities in leukemia: a national study. Cancer Causes Control. 2012;23:1831-1837.
8. Linabery AM, Blommer CN, Spector LG, et al. ARID5B and IKZF1 variants, selected demographic factors and childhood acute lymphoblastic leukemia: a report from the Children's Oncology Group. Leuk Res. 2013;37:936-942.
9. Xu H, Cheng C, Devidas M, et al. ARID5B genetic polymorphisms contribute to racial disparities in the incidence and treatment outcome of childhood acute lymphoblastic leukemia. J Clin Oncol. 2012;30;7:751-757.
10. Darmawikarta D, Pole JD, Gupta S. The association between socioeconomic status and survival among children with Hodgkin and non-Hogkin lymphomas in a universal health care system. Pediatr Blood Cancer. 2013;60(7):1171-1177.