Race and Sex Differences in PRMT6 Expression in Lung Tumors in Relation to Neighborhood Violence

Lung cancer is the leading cause of cancer-related death. The incidence and mortality rates are higher for Black men than for White men. Protein arginine methyltransferase 6 (PRMT6) is known to be associated with lung cancer tumorigenesis and prognosis, and different levels of PRMT6 expression by race and sex may explain lung cancer disparities among Black men. To examine differences in PRMT6 by neighborhood violence as social stress, we obtained 88 formalin-fixed, paraffin-embedded tissue sections of patients with lung cancer. Using immunohistochemistry, samples were stained and scored [histochemical score (H-score)] for PRMT6 levels. Logistic regression was used to examine the likelihood of having a high H-score (≥ median) by race and sex, controlling for age, smoking status, tumor type, grade, stage at diagnosis, and neighborhood homicide rate. The odds of having a high H-score were higher for Blacks than Whites, but there was no sex difference when controlling for tumor characteristics. High homicide was negatively associated with high H-scores. Controlling for all other variables, the odds ratio (OR) of having a high H-score for Black versus White males was 7.8, and the OR for Black versus White females was 1.8 for the low homicide group. The ORs for both Black versus White males and Black versus White females were more than 3 times higher for the high homicide group. Overexpression of PRMT6 may explain the lung cancer disparity in Black men. Exposure to social stress may contribute to higher levels of PRMT6. Social and biological differences affecting race and sex groups need further investigation.

This study explores the impact of living in a high violence neighborhood, which may contribute to the elevated risk of lung cancer and tumor prognosis. Epigenetic modification may be a mechanism linking social exposure and biological changes. Addressing neighborhood-level social stress exposure may improve the prevention and intervention of lung cancer.