背景胆红素是一种有效的抗氧化剂，在许多疾病中具有保护作用。我们研究了血清胆红素 (SB) 水平、吸烟（SB 低的已知原因）和呼吸消化道癌症（肺癌 (LC) 和头颈癌 (HNC)）之间的关系。方法 我们使用 393,210 名参与者的数据检查了 SB、LC 和 HNC 之间的关联，这些参与者来自真实世界、多样化、去识别化的数据存储库和与 UCLA Health 系统相关的生物库。我们采用回归模型、倾向评分匹配和多基因评分来研究 SB、吸烟、LC 和 HNC 之间的关联和相互作用。结果 与从不吸烟者相比，目前吸烟者的 SB 较低（-0.04mg/dL，95% CI：[-0.04，-0.03]）。与无癌对照相比，HNC 和 LC 病例中观察到较低的 SB 水平（分别为 -0.10 mg/dL、[-0.13, -0.09] 和 - 0.09 mg/dL，CI [-0.1, -0.07]）调整吸烟后仍坚持。 SB 水平与 HNC 和 LC 风险呈负相关（SB 每 SD 变化的 OR 分别为 0.64，CI [0.59，0.69] 和 0.57，CI [0.43，0.75]）。最后，SB 的多基因评分 (PGS) 与 LC 相关（SB-PGS 每 SD 变化的 OR：0.71，CI [0.67，0.76]）。结论 低 SB 水平与 HNC 和 LC 风险增加相关，与吸烟的影响无关。此外，吸烟与 SB 对 LC 风险有很强的交互作用。最后，基因预测的低 SB（使用多基因评分）与 LC 呈负相关。这些发现表明 SB 可以作为 LC 和 HNC 的潜在早期低成本生物标志物。与吸烟的相互作用表明，与从不吸烟者相比，胆红素较低的吸烟者患 LC 的风险可能更高，这表明 SB 在对有 LC 风险的患者进行风险分层时有用。最后，多基因评分分析的结果表明 SB 的遗传控制与 LC 发展风险之间存在潜在的共同生物学途径。

Background Bilirubin is a potent antioxidant with a protective role in many diseases. We examined the relationships between serum bilirubin (SB) levels, tobacco smoking (a known cause of low SB), and aerodigestive cancers, grouped as lung cancers (LC) and head and neck cancers (HNC). Methods We examined the associations between SB, LC, and HNC using data from 393,210 participants from a real-world, diverse, de-identified data repository and biobank linked to the UCLA Health system. We employed regression models, propensity score matching, and polygenic scores to investigate the associations and interactions between SB, tobacco smoking, LC, and HNC. Results Current tobacco smokers showed lower SB (-0.04mg/dL, 95% CI: [-0.04, -0.03]), compared to never-smokers. Lower SB levels were observed in HNC and LC cases (-0.10 mg/dL, [-0.13, -0.09] and - 0.09 mg/dL, CI [-0.1, -0.07] respectively) compared to cancer-free controls with the effect persisting after adjusting for smoking. SB levels were inversely associated with HNC and LC risk (ORs per SD change in SB: 0.64, CI [0.59,0.69] and 0.57, CI [0.43,0.75], respectively). Lastly, a polygenic score (PGS) for SB was associated with LC (OR per SD change of SB-PGS: 0.71, CI [0.67, 0.76]). Conclusions Low SB levels are associated with an increased risk of both HNC and LC, independent of the effect of tobacco smoking. Additionally, tobacco smoking demonstrated a strong interaction with SB on LC risk. Lastly, genetically predicted low SB (using a polygenic score) is negatively associated with LC. These findings suggest that SB could serve as a potential early and low-cost biomarker for LC and HNC. The interaction with tobacco smoking suggests that smokers with lower bilirubin could likely be at higher risk for LC compared to never smokers, suggesting the utility of SB in risk stratification for patients at risk for LC. Lastly, the results of the polygenic score analyses suggest potential shared biological pathways between the genetic control of SB and the risk of LC development.