Known risk factors, such as smoking, obesity and hypertension, do not explain variations in the incidence of clear cell renal cell carcinoma (ccRCC) between different geographical regions. A new study reports that the somatic mutation profiles of ccRCC differ between countries, which indicates substantial geographical variations in mutagenic exposures.
To investigate mutational signatures in ccRCC, Senkin and coauthors sequenced the ccRCC genomes of 962 patients from 11 countries worldwide. The somatic mutation burdens of the ccRCCs varied between countries, with the highest burden in Romania. In most cases of ccRCC from Romania, Serbia and Thailand, but only rare cases elsewhere, the researchers identified mutational signatures that are characteristic of exposure to aristolochic acids, which are known carcinogens. By contrast, more than 70% of cases of ccRCC from Japan had a mutational signature of unknown cause, which was identified in less than 2% of cases from other countries. Another mutational signature of unknown aetiology was identified in cases of ccRCC from all 11 countries. The average country-specific mutation load attributable to this signature positively correlated with the country-specific age-standardized incidence of kidney cancer. Associations were also identified between mutational signatures and tobacco smoking, but not between mutational signatures and other ccRCC risk factors.
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- Source: https://www.nature.com/articles/s41581-024-00855-9