February 09, 2017
3 min read

Genomic alterations similar between black and white patients with lung cancer

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Genomic alterations appeared similar in black and white patients with lung adenocarcinoma and lung squamous cell carcinoma, according to results of a genomic cohort study.

These results suggest that different mutational profiles do not contribute to the increased incidence of lung cancer in black patients compared with white patients, according to researchers.

Laura MacConaill

“We found that there were no major differences in the genomic alterations that drive lung cancer in these groups and, therefore, targeted therapies and biomarker-driven clinical trials should benefit patients in both groups,” Laura MacConaill, PhD, scientific director at the Center for Cancer Genome Discovery of Dana-Farber Cancer Institute, told HemOnc Today.

Lung cancer is the leading cause of cancer death in the United States. The lung cancer mortality rate is higher in black patients than white patients, but it is unknown why this is the case, MacConaill said.

“We wanted to investigate whether there were differences at the genetic level between lung cancers from the different groups,” MacConaill said.

In this 5-year study of lung cancer disparities — funded by the NIH — MacConaill and colleagues profiled and analyzed 509 lung cancer tumors specimens (319 adenocarcinomas; 142 squamous cell carcinomas) from 245 black patients and 264 white patients treated at Baptist Cancer Center in Memphis, Tennessee, between 2004 and 2012.

Of the patients, 273 were women (black, n = 129; white, n = 144) and 236 were men (black, n = 116; white, n = 120). The majority of patients had stage I (n = 205) or stage II (n = 98) disease.

The tumor samples underwent DNA isolation, and researchers used the OncoPanel platform to sequence the cancer genes at Dana-Farber Cancer Institute.

“Our ability to do [this study] in a comprehensive manner was, in part, due to the well-annotated clinical cohort of patient samples from the same geographic location in the United states, as well as performing the genomic testing using a robust clinical-grade sequencing test,” MacConaill said.

The researchers identified four mutational signatures in the cohort, which were strongly correlated with previously characterized signatures of smoking, aberrant APOBEC activity, mismatch repair and aging, and ultraviolet radiation exposure.

Analysis showed that no signature was associated with ancestry, “suggesting that the mutagenic processes are similar in lung tumors from black and white populations in lung adenocarcinoma or lung squamous cell carcinoma,” the researchers wrote.

Researchers then examined the mutations frequencies in 313 adenocarcinomas and 138 squamous cell carcinomas — which excluded ten samples from patients whose ancestry was not confirmed in the principal component analysis — to assess the relationship between ancestry and mutation status.

Clinical variables were not significantly associated with ancestry in either tumor type, except the number of smoking pack-years.

The number of putative somatic mutations, percentage of genes amplified or the percentage of genes deleted per tumor — along with other quality control metrics — also were not associated with ancestry.

Researchers then compared mutational frequencies of the cohort with frequencies from tumors observed in The Cancer Genome Atlas and other studies. Among patients with lung adenocarcinoma, TP53 had a higher mutation frequency in black patients with (P = .02), NFI had a lower frequency in tumors from white patients (P = .045), and KEAP1 had lower frequencies in tumors from both black and white patients (P < .001). No significant differences were observed between the lung squamous cell carcinomas from black and white patients compared with The Cancer Genome Atlas using the Fisher exact test.

The researchers noted that the sequencing panel was limited to cancer genes and did not enable them to perform more comprehensive ancestral inference and classification. However, single-nucleotide variants were captured in the cancer genes likely to be inherited due to high frequency in nondisease tissue from the Exome Aggregation Consortium database.

“Overall, these results suggest that differences in exomic mutations do not contribute to the observed racial disparities in incidence and mortality between black and white populations,” the researchers wrote. “Further investigation into other genomic factors, such as mutations in noncoding regions, epigenetic alterations and gene expression changes or other socioeconomic variables beyond smoking behavior and access to health care, may be required to fully explain these disparities.” – by Melinda Stevens

For more information:

Laura MacConaill, PhD , can be reached at Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 450 Brookline Ave. Boston, MA 02215; email: laura_macconaill@dfci.harvard.edu.

Disclosures: MacConaill reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.