Plasma tRNA-derived small RNAs mediated the association between benzo[a]pyrene exposure with lung cancer risk among Chinese adults from a case-control study

Exposure to benzo[a]pyrene (BaP) could lead to the development of lung cancer, but the potential mechanisms are complex and remain largely unclear. Plasma tRNA-derived small RNA (tsRNA), a new type epigenetic biomarker of cancer, might link environment exposure with lung cancer. Based on this case-control study of 272 participants recruited from China, we aim to reveal the plasma tsRNA signature of lung cancer and their mediation effects on BaP-induced lung cancer. We sequenced tsRNA profiles and detected the adducts of Benzo[a]pyrene diol epoxide-albumin (BPDE-Alb) in plasma samples. We applied linear regression models to estimate associations between the adducts of BPDE-Alb, normalized tsRNA and the risk of lung cancer. We used mediation analysis to explore the mediation roles of tsRNAs in BaP-associated lung cancer. We identified 104 tsRNAs significantly related to the risk of lung cancer (Bonferroni adjusted P < 0.05). Among these 104 tsRNAs, 17 tsRNAs were expressed at different concentrations between before and after lung cancer surgery groups with |fold change| > 2 at Bonferroni adjusted P < 0.05. In addition, of these 17 tsRNAs, the adducts of BPDE-Alb were associated with 5'-M-tRNA-Glu-CTC-1-1-L36, i-M-tRNA-Met-CAT-1-1-L24_pos29 and i-M-tRNA-Ala-AGC-2-2-L16_pos16, which could mediate a separate 40.8 %, 39.1 % and 36.8 % of the association between BaP exposure with lung cancer. Our study identified tsRNAs potentially mediating BaP-associated lung cancer development, and revealed tsRNAs as promising biomarkers of lung cancer.