Summary
A medRxiv preprint analysing 520 tumour genomes from eight countries reports similar mutational landscapes in oesophageal and gastroesophageal-junction adenocarcinomas. It also links reflux-associated mutation signatures with obesity in oesophageal adenocarcinoma and reports geographic differences in other signatures.
A medRxiv preprint reports that oesophageal adenocarcinomas and cancers at the gastroesophageal junction share a broadly similar pattern of tumour mutations. The researchers analysed 520 whole genomes from tumours in eight countries, finding that two mutation signatures previously associated with reflux dominated the cancers studied. In oesophageal adenocarcinoma, those signatures were also linked to obesity.
A shared reflux-linked mutational landscape
A mutational signature is a recurring pattern of DNA changes that can provide clues about the processes that have altered cells. The study identified SBS17a and SBS17b as dominant signatures in both oesophageal adenocarcinoma (EAC) and gastroesophageal-junction (GEJ) tumours. The authors say these signatures have previously been associated with reflux in these cancers.
In EAC, the signatures were linked to obesity. The researchers interpret this finding as supporting an indirect role for obesity: it may exacerbate reflux, which in turn is associated with the mutation patterns. The genomic association does not by itself establish that obesity directly produces those mutations.
Geographic differences and risk interpretation
Although the overall mutational landscapes were similar, the analysis found geographic differences. Signatures connected to endogenous cellular functions—processes originating within the body’s own cells—were enriched in populations with high incidence of these cancers. The finding points to variation in the mutational processes represented in tumours across populations; it does not identify a specific cause for those differences.
The study did not find a direct mutational footprint of tobacco smoking in the tumours analysed. The authors suggest that established risk factors may also influence EAC and GEJ through effects that do not leave a detectable mutation pattern. That result should not be read as showing that smoking has no role in these cancers: the finding concerns a direct genomic footprint in this analysis.
The work is posted as a medRxiv preprint, so its results have not yet undergone peer review. Its findings describe mutation patterns and associations, rather than establishing the causes of the geographic differences or the pathway linking obesity and reflux.