Pan-cancer mutational signatures' correlation with cancer racial disparities 

Minorities are disproportionately affected by cancer due to disparities in socioeconomic status, environmental conditions, and genetics. While conventional measures of cancer disparities focus on occurrence rates and mortality rates, analyzing genomic data has been less common. Researchers have recently identified mutational signatures as markers of both internal and external cancer-causing agents, leading to significant advancements in genomic cancer research.

These disparities resulting from unequal exposure to environmental pollutants and viral infections are evident in mutational signatures. By examining a comprehensive mutation dataset from a large cancer pool, we investigated mutational signatures in relation to racial disparities. Specifically, we explored the link between mutational signatures and geospatial environmental exposures, including 449 air pollutants documented by the US Environmental Protection Agency between 2007 and 2017. We also considered the infection status of Hepatitis B and C viruses, as well as Human Papillomavirus.

Our analysis revealed clear variations in the frequencies of key oncogenic gene mutations among different racial groups. For instance, TP53 mutations were more prevalent in Black breast cancer patients (46%) compared to White patients (31%). These differences in individual genes extended to mutational signatures, with eleven exhibiting racial disparities. Importantly, the aflatoxin mutational signature, a known liver cancer-causing agent, was more present in Asian liver cancer patients than in White patients (adjusted P = 0.002). Further investigation revealed that Hepatitis infection exacerbated the aflatoxin mutational signature in Asian patients (HBV P = 0.006, HCV P = 0.004), indicating a genetic or genomic vulnerability among Asians concerning aflatoxin exposure.

Additionally, our geospatial analysis consistently showed that exposure to air pollutants increased levels of specific mutational signatures and decreased disease-specific prognoses for patients. These findings establish significant connections between mutational signatures and various carcinogenic exposures, including pollutants and oncovirus infections. Most importantly, these associations disproportionately affect minority populations in the United States.