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Out of order: (Not a) Goo goo g男ob
May 2017
by Randall C Willis  |  Email the author
SHARING OPTIONS:

I am he as you are he as you are me, and we are all together—unless we’re talking about cancer.
 
Although Eggmen and Walruses didn’t factor highly into many of the talks featured at the AACR 2017 conference in Washington, D.C., last month, neither it seems did many people who weren’t Caucasians of European descent.
 
For whatever reason, people of African, Central and South American, Native American and Asian descents have not featured prominently in cancer research, and their absence may be leading to significantly poorer outcomes in the face of cancer, including higher death rates.
 
Access to care, largely tied to socio-economic status, has borne much legitimate blame in these outcomes.
 
High-infrastructure diagnostic resources, life-saving biologics and long-term treatment regimens are not accessible to the majority of the world’s population. Similarly, living conditions often expose disparate populations to a variety of risk factors simply not at play in much of North America and Europe.
 
But even in situations where the playing field is more even—such as between communities within the United States—the relative rates of some cancers and the likelihood of positive outcomes for Caucasian populations vs. other groups can be quite heavily skewed in favor of the Caucasians.
 
As part of a larger AACR presentation on the need for diverse populations in cancer studies, Eimear Kenny of Mount Sinai’s Icahn School of Medicine noted that certain groups have been almost completely excluded from consideration.
 
Citing the European Molecular Biology Laboratory database, she noted that as of December 2016, almost 50 million subjects had participated genome-wide association studies (GWAS) globally, and yet 76 percent of those participants were identified as Caucasian, while another 20 percent were East Asians (a growing sector).
 
The remaining four percent, described as “Other,” largely comprised Africans and non-Caucasian peoples of the Americas.
 
Thus, in trying to correlate cancer with human genetics, how can we even begin to make headway while ignoring vast tracts of the global population?
 
In the same session, Case Western’s Kishore Guda described his group’s efforts to understand colorectal cancer (CRC) in the African-American population, where the disease occurs 25 percent more often and has 50 percent higher mortality than in non-Hispanic Caucasians. As Guda highlighted, since 1960, the rates of CRC have dropped 39 percent in Caucasian-American men but increased 28 percent in African-American men, and the latter group consistently perform more poorly in clinical trials on Stage II and III CRC.
 
To better understand what was happening, Guda’s group set out to study the mutational landscape of CRC in African-Americans, noting that in four major CRC sequencing studies, only two of 333 CRCs examined were from African-American patients.
 
From an initial analysis of almost 2700 protein-altering mutations across more than 2100 genes, the researchers narrowed their focus to 15 mutations that occurred predominantly in African-Americans versus Caucasian-Americans (41 vs 15 percent; PNAS), and each of which led to poorer outcomes in Stage I to III CRC patients (JNCI). Of the 15, four mutations were completely specific to African-Americans.
 
Further work is required to determine whether these mutations predominate in other populations and/or can serve as markers and possibly act as mediators of adverse outcomes in African-American populations.
 
These presentations were just two of several that highlighted the challenges of understanding cancer through a relatively monochromatic lens. Slowly, the scientific community is starting to shine light on these issues, as exemplified by efforts such as the 1000 Genomes Project, designed to broadly catalogue human genetic variation across the globe.
 
But in this so-called Era of Precision Medicine—and I will continue to describe it as so-called until I see a systematic approach to molecular analysis in clinical trials and drug discovery—it is unconscionable that we, however passively, continue to treat the majority of people on this planet as poly-pigmented Caucasians.
 
Perhaps I should cut research some slack, however, as we have only recently begun to recognize women as more than genitally diverse men and children as more than metrically diminished adults.
 
But the sooner we acknowledge that these are not simply tans from standing in the English rain, the sooner we will begin to close the very serious gaps in outcomes for people suffering around the world.

Randall C Willis can be reached by email at willis@ddn-news.com

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