Integrating Race, Ethnicity, and Now Ancestry Into Cancer Research—Why Does it Matter?

Reading time: 4 minutes

Aileen I Fernandez

Cancer health disparities are prevalent in the United States and are defined as “adverse differences between certain population groups in cancer measures”. It is well known that there are variations in cancer burden associated with racial/ethnic identity and that this is due to many factors. Among these are social determinants of health –“the conditions in the environments where people are born, live, learn, work, play, worship, and age that affect health, functioning, and quality of life”, behavior, and importantly, biology and genetics. 

As I’ve previously discussed, data from a 2009 study showed that even after adjusting for factors such as age, stage, grade, and poverty index, Black women with triple-negative breast cancer (TNBC) still have a worse prognosis in comparison to White women, indicating that the disparity here is due not only to socioeconomic factors but also biological factors. So how can researchers properly address this? 

To begin, it is important to clear up some common misconceptions about the language used. Often, the terms race, ethnicity, and ancestry are used interchangeably, which is incorrect:

• Race is a social construct and refers to physical appearances, such as skin and eye color (examples include Black, White, American Indian, Asian, Native Hawaiian, or Other Pacific Islander)
• Ethnicity is having a common cultural heritage, language, social practice, and traditions (examples include Hispanic or Latino)
• Ancestry is inferred using ancestry informative markers (AIMs), (based on genomic data)

Studies have shown that there are differences between self-reported race compared to AIMs.  In 2014, the 1000 genomes project published part of a multi-year, international, project where they categorized “superpopulation groups” (African (AFR), American Admixed (AMR), East Asian (ASN), European (EUR), South Asian (SAN)) based on AIMs and comparing them to self-reported race and ethnicities. Some of their interesting findings include: 

• Self-reporting African Americans can have drastically different levels of African or European ancestry
• Self-identified African Americans have up to 99% of European ancestry; self-identified European Americans have substantial admixture from African ancestry
• African ancestry in the Latino population ranges between 3% in Mexican Americans to 16% in Puerto Ricans 
• In African American or Latino populations, self-reported ancestry may not be as accurate as direct assessment of individual genomic information in predicting treatment outcomes

These findings highlight the difference between race and ethnicity versus ancestry, but how do these impact cancer diagnoses? 

There have been several genome-wide association studies (GWAS) that have shown ancestry linkages with breast cancer. For example, HER2+ breast cancer (a subtype of breast cancer) was reported to be positively associated with Indigenous American Ancestry in Latin American women. Additionally, women with higher Indigenous American ancestry were shown to have an increased risk of breast cancer-specific mortality, and the TNBC transcriptome in some Latina patients is related to alternative critical signaling pathways and biological functions. This means that genetic ancestry can provide biological insights into these already observed differences in cancer burden. An interesting study published in 2020 studied the Women’s Health Initiative, a 160k+ person cohort, and found that Black women have (amongst numerous findings) a higher density of pro-tumor immune cells and that this may be a result of evolutionary selection for a more robust immune response in patients of African geographic ancestry.

Overall, there are several pros and cons to using ancestry versus self-identified race when studying cancer. Pros include a contribution towards the goal of personalized medicine, the applicability of genetic associations in understanding disease pathways and processes rather than simply observing health differences, and the removal of confounding environmental factors, i.e. socioeconomic status, neighborhood environment, psychosocial factors(such as perceived stress or discrimination, healthcare provider bias). On the flip side, cons include high cost (for now) and ease of use, the risk of false attribution of causality, stigmatization of high-risk populations, and underestimation of risk for other populations.

Due to the broad definitions of race and ethnicity, and the fact that humans can identify with multiple races, considering ancestry can improve the way we identify and address the biological causes behind these health disparities.  

Edited by Kayla Snare

Works Discussed

Marker, Katie M., et al. “Human epidermal growth factor receptor 2–positive breast cancer is associated with indigenous american ancestry in Latin American women.” Cancer research 80.9 (2020): 1893-1901.

Fejerman, Laura, et al. “Genetic ancestry and risk of mortality among US Latinas with breast cancer.” Cancer research 73.24 (2013): 7243-7253.

Sugita, Bruna M., et al. “Integrated copy number and miRNA expression analysis in triple negative breast cancer of Latin American patients.” Oncotarget 10.58 (2019): 6184.

Jones, Veronica C., et al. “African Ancestry and Triple-Negative Breast Cancer in the Women’s Health Initiative.” The American Surgeon (2020): 0003134820949518.