Understanding Ethnicity in Lung Cancer: Are We There Yet?
Lung cancer remains the leading cause of cancer mortality globally. Thanks to tobacco control efforts by the World Health Organization and others, great strides have been made in reducing overall prevalence. In spite of this, mortality rates continue to widen between non-Caucasians and Caucasians around the world. Evidence continues to confirm that beyond smoking history, disparities in socioeconomic strata are leading factors in lung cancer risk around the globe. Looking beyond socioeconomic strata, however, colleagues in Brazil and the US recently remind us of the importance of understanding ethnicity in lung cancer. Are we there yet? No.
Over a decade ago, I raised the question of, “Is there ethnicity in breast cancer?” Today, the automatic response is, “Of course.” However, when we first began to try to answer the question in a global breast cancer medical thought leadership study, the answer was not that obvious. We observed a potentially higher likelihood of triple negative breast cancer (TNBC) in younger, non-Caucasian women around the globe. We had hundreds of testimonials from physicians of non-Caucasian patients tell us, “NCCN and St. Galen’s Guidelines don’t work in our patients”, “We see younger women with more aggressive tumors,” and similar comments. When we tried to confirm these observations through epidemiologic and genomic data, they simply were lacking. This kicked off a groundswell of additional research through the National Cancer Institute (NCI), the Ethnic Research Initiative (ERI), and others. 9 years later, NCI confirmed that there was indeed ethnicity in breast cancer and especially in TNBC. Meanwhile, the study of the impact of ethnicity in other cancers also grew.
At a 2011 U.S. President’s Cancer Panel meeting, Dr. Cheryl Wellman discussed her most recent research for NCI in New Mexico: she discovered the correlation between higher relapse rates in children with Acute Lymphoblastic Leukemia (ALL) and ancestry factors among Native Americans and Hispanic Americans. The research team went back at least 5 generations to observe that relapse rates in children who were admixes with European Caucasian ancestries were significantly lower than those of native populations. This insight has stayed with me since.
That same year, Drs. Zhou and Christiani published a review article about ethnic differences in epidemiology and clinical behaviors of lung cancer between East Asians and Caucasians. Their study reconfirmed that Asians with non-small cell lung cancer have a higher proportion of never-smokers and younger age of onset, yet Asian ethnicity was a favorable prognostic factor for overall survival. They concluded by saying, “The exact mechanisms behind these differences are not clear. These ethnic differences should be take into account when conducting global clinical trials that include different ethnic populations.”
Most recently, I was reminded again of the need to understand this impact of ethnicity in lung cancer. At least three recent studies and meta analyses demonstrate that even after controlling for genetic mutations and socioeconomic risk factors, African Americans are at higher mortality risk than their Caucasian counterparts. Two of the key challenges to doing such research in the US and around the world, of course, are participant access to such research, and research funding. Beyond this, the AA community in the US continues to be haunted by suspicions about participating in research stemming, in part, from the long-ago government-led Tuskegee syphilis trial.
These hurdles should not stop of from digging deeper into implications of ethnicity in lung cancer. Drs. Araujo and Cardone say it most elegantly in the conclusion to their 2017 study:
“There is clear need to advance research on ethnically diverse and admixed populations such as AAs, and comprehend how lung cancer develops in each niche. Large population studies may be needed to really define genomic peculiarities, and more comprehensive panels may be necessary to define the landscape as well. In an era when precision medicine becomes a common goal in oncology, focus on the interaction of genomics with objective measures of ancestry should not be lost.”