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Cancer death rates vary among population groups. Underserved populations continue to experience an excessive burden of lethal cancers that is largely explained by health care disparities. Yet the prominent role of advanced stage disease as a driver of cancer survival disparities may indicate that some cancers are more aggressive in certain population groups than others. The tumor mutational burden can show large differences among patients with similar stage disease but differences in race/ethnicity or residence. These dissimilarities may result from environmental or chronic inflammatory exposures, altering tumor biology and the immune response. We will discuss the evidence that inflammation and immune response dissimilarities among population groups contribute to cancer disparities and how they can be targeted to reduce these disparities.