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African American genes linked to worse survival in HNSCC
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African American ancestry is genetically linked to worse survival in patients with head and neck squamous cell carcinoma, according to a study published in Cancer.
“African American and white HNSCC patients possess distinct genetic ancestries,” Meganathan P. Ramakodi, PhD, postdoctoral associate of the cancer prevention and control program at Fox Chase Cancer Center–Temple Health, and colleagues wrote. “Our recent genomic analysis of laryngeal cancer in African American and white patients revealed that distinctive genetic ancestry corresponds to molecular differences in the laryngeal cancers arising in these two populations. We tested the hypothesis that ancestry-related genomic elements are associated with HNSCC survival disparities because of altered gene expression in DNA damage response genes, which affects the sensitivity to chemotherapy and/or radiotherapy.”
The researchers analyzed ancestry-informative single-nucleotide polymorphisms, methylation, RNA sequencing and copy number variation data in 316 patients with oral cavity or laryngeal cancer, evaluating the relationship between expression quantitative trait loci and DFS.
Researchers identified five ancestry-related single-nucleotide polymorphisms as cis-expression quantitative trait loci in the POLB gene. Genotypes with the African allele showed a greater POLB expression compared with the homozygous white allele genotype (P < .001). A replication study showed a “statistically significant difference” in expression of POLB between ancestries (P = .002).
Expression quantitative trait loci was associated with OS (P < .037) and DFS (P = .018) among patients with oral and laryngeal cancer who received platinum-based chemotherapy and/or radiotherapy. The genotypes containing the African allele were associated with worse OS and DFS compared to those containing the white allele.
“Disparities in cancer risk and survival outcomes among African Americans are generally attributed to factors such as socioeconomic status and geography,” Camille Ragin, PhD, MPH, associate professor and head and neck cancer TRDG member at Fox Chase Cancer Center–Temple Health said in a press release. “Our findings suggest that in addition to these factors, there is an association between ancestry and survival rate disparities for the head and neck cancers were studied.”
“Our study reveals a clear association between African ancestry-related genetic factors and poor treatment outcomes in African American patients with HNSCC who were treated with platinum-based chemotherapy and/or radiotherapy,” the researchers wrote. “The validation of our findings in a larger independent cohort of subjects would help to further strengthen and establish their significance.” – by Andy Polhamus
Disclosure: Ramakodi reports no relevant financial disclosures. See the full study for a list of all other researchers’ relevant financial disclosures.
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